Symposium Organizers
Larry Nagahara National Cancer Institute
Thomas Thundat Oak Ridge National Laboratory
Sangeeta Bhatia Massachusetts Institute of Technology
Anja Boisen Technical University of Denmark
Kazunori Kataoka The University of Tokyo
FF1: Nanotechnology for Biomedical Applications
Session Chairs
Sangeeta Bhatia
Anja Boisen
Larry Nagahara
Thomas Thundat
Monday PM, December 01, 2008
Room 304 (Hynes)
9:30 AM - **FF1.1
The Workings of NCI Nanotechnology Alliance for Cancer - an Opportunity for a New Class of Diagnostic and Therapeutic Solutions Based on Nanotechnology.
Piotr Grodzinski 1
1 , National Cancer Institute, Bethesda, Maryland, United States
Show AbstractNational Cancer Institute is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose and treat cancer. Novel and multi-functional nanodevices will be capable of detecting cancer at its earliest stages, pinpointing its location within the body, delivering anticancer drugs specifically to malignant cells, and determining if these drugs are effective. Functionalized nanoparticles would deliver multiple therapeutic agents to tumor sites in order to simultaneously attack multiple points in the pathways involved in cancer. Such nano-therapeutics are expected to increase the efficacy of drugs while dramatically reducing potential side effects. In vivo biosensors would have the capability of detecting tumors and metastatic lesions that are far smaller than those detectable using current, conventional technologies. Furthermore, they will provide rapid information on whether a given therapy is working as expected.In order to further these research goals, NCI Alliance for Nanotechnology in Cancer has been formed in 2004. The Alliance is investing $144.3 million over the next 5 years to pursue applied nanotechnologies for cancer detection, therapy, and prevention with an aim to achieve clinical translational stage of these technologies towards culmination of the program. The Alliance funds Centers of Cancer Nanotechnology Excellence, the development of nanotechnology platforms, and intramural Nanotechnology Characterization Laboratory (NCL). NCL provides a spectrum of data on the physical parameters and pharmacological and toxicological characteristics of clinically promising nanomaterials. The eight CCNEs – Centers of Cancer Nanotechnology Excellence represent prime research institutions in the US: Carolina Center of Cancer Nanotechnology Excellence at the University of North Carolina, Center for Cancer Nanotechnology Excellence Focused on Therapy Response at Stanford University, Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer at the University of California, San Diego, Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology at Emory University and Georgia Institute of Technology, MIT-Harvard Center of Cancer Nanotechnology Excellence at MIT and Harvard University, Nanomaterials for Cancer Diagnostics and Therapeutics at Northwestern University, Nanosystems Biology Cancer Center at California Institute of Technology, and the Siteman Center of Cancer Nanotechnology Excellence at Washington University.This presentation will describe the details behind the organization and science and technology of the Alliance.
11:30 AM - **FF1.2
Nanoparticles as Gene Regulation Materials
Chad Mirkin 1
1 , Northwestern University, Evanston, Illinois, United States
Show Abstract12:00 PM - FF1.3
DNA Encapsulation within Redox-Active Deconstructable Polymer Microcapsules.
Alisa Becker 1 , Alexander Zelikin 1 , Angus Johnston 1 , Kim Wark 2 , Frank Caruso 1
1 Chemical and Biomolecular Engineering, The University of Melbourne, Melbourne, Victoria, Australia, 2 Preventative Health Flagship & Division of Molecular and Health Technologies, CSIRO, Melbourne, Victoria, Australia
Show AbstractEmerging biomedical technologies such as nucleic acid therapeutics can benefit from encapsulation within polymeric microcapsules. Successful in vivo delivery of nucleic acids requires the DNA to be both protected from nucleases and directed to the site of action. DNA can be protected by encapsulation within a nano-thin polymer capsule. Hollow polymeric capsules in the size range of 300 nm to 5 μm can be formed using the layer-by-layer (LbL) technique for thin film formation. Thiol -functionalized poly(methacrylic acid) (PMA) and poly(vinylpyrrolidone) were deposited alternately on a sacrificial colloidal template utilizing hydrogen bonding for thin film buildup. After cross-linking and core removal, hollow capsules are obtained. Using disulfide cross-links between PMA layers gives rise to redox-active deconstructable capsules. These capsules take advantage of the redox chemistry inside cells to release their cargo. Variation of the thiolation degree and molecular weight of PMA can control the capsule properties and cargo release. DNA was encapsulated within semipermeable capsules by adsorption of DNA onto amine-functionalized silica (SiO2+) particles, followed by thin film formation using LbL, and removal of the sacrificial SiO2+ particles. Several types of DNA have been encapsulated within microcapsules, including plasmid, linear double-stranded DNA and short oligonucleotides. DNA that was encapsulated and subsequently released was active in polymerase chain reactions and was also transcriptionally active in E.coli, indicating minimal functional loss.
12:15 PM - FF1.4
Self-signalling Antibodies for Specific Bacterial Detection.
Sarah Wagstaffe 1 , D. Jason Riley 1
1 Materials Department, Imperial College London, London United Kingdom
Show AbstractA real-time, multiparametric assay to allow the assessment of bacterial load and diversity has been developed. The measurement of bacterial indicators has been achieved using antibodies to create a digital instrument signal. Bispecific antibodies to suitable reporter molecules and bacterial indicators have been generated, where molecular binding of a bacterial indicator to one arm displaces a previously bound reporter molecule from the adjacent site (Randle et al. 2004). The concentration of the reporter released upon bacterial binding is then evaluated by electroanalysis.Citrate-stabilized gold nanoparticles with a diameter of 20nm were synthesized using the Faraday method and bispecific antibodies to the species have been generated. Thus, upon binding of a bacterial indicator, the nanoparticle is released into solution. Sensitive detection of the released gold has been achieved at a modified carbon paste electrode with a preconcentration step.
12:30 PM - FF1.5
A Comparison of 2-part and 3-part Nanoparticle-Based Sensors.
Jorge Chavez 1 , Wanda Lyon 1 , Nancy Kelley-Loughnane 1 , Yaroslav Chushak 1 , Morley Stone 1
1 Human Effectiveness Directorate, Air Force Research Laboratory, Wright-Patterson Air Force Base, Ohio, United States
Show AbstractThere has long been a drive to produce sensors with ever-increasing sensitivity and selectivity, while also achieving robustness and ease of use. Nanoparticle-based sensing approaches have generated a great deal of attention and excitement, because they possess such qualities. For these assays to function properly, it requires the integration of molecular recognition motifs with materials possessing outstanding optical properties. Aptamers are DNA or RNA sequences that bind analytes with high specificity, which makes them a logical choice as recognition elements. Changes in the surface plasmon resonance of gold nanoparticles as a function of interparticle distance, has been used as an optical signal to detect the presence of different species in solution visually. In this work, we coated gold nanoparticles with short oligonucleotides and aptamers for the design of sensors that can be used under different conditions, including salt concentration, pH and temperature. Aptamer sensors against 3 different analytes were developed using this approach 1) riboflavin, as a general indicator of human metabolism, 2) ricin, a toxin that is of broad interest, and 3) theophylline, an adenosine antagonist. Our designs are based on two approaches, the first method consisted of the use of an aptamer to link gold particles coated with oligonucleotides that were complementary at the 5’ and 3’ ends of the linker, i.e., 3-part design. The second involved the direct attachment of one end of the aptamer to the nanoparticles, followed by its crosslinking with nanoparticles coated with a complementary sequence to the free-end of the aptamer, i.e., 2-part design. The formation of sensing aggregates resulted in a blue-shift color change. In both cases, the presence of analyte promoted a change in the conformation of the aptamer resulting in the dissociation of the aggregates, which subsequently translated into a change in the color of the suspensions from blue to red. In this presentation, we will compare the advantages and disadvantages associated with a 3-part versus a 2-part nanoparticle-oligonucleotide reporting assay.
FF2: Nanoparticles for Drug Delivery
Session Chairs
Piotr Grodzinski
Larry Nagahara
Monday PM, December 01, 2008
Room 304 (Hynes)
2:30 PM - **FF2.1
Development of Polymeric Nanoconjugates for Controlled Drug Delivery.
Rong Tong 1 , Jianjun Cheng 1
1 Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
Show AbstractPolymeric nanoparticles are promising carriers for the delivery of chemotherapeutics for cancer therapy because they are able to carry large payload of therapeutic modality, extravasate leaky tumor vasculature, and mediate sustained drug release in tumor tissues. Of a handful of nanoparticulate carriers being studied, polymeric nanoencapsulates are particularly promising because they can be readily prepared through the co-precipitation of hydrophobic polymers and small molecule drugs in a process called nanoprecipitation. However, nanoencapsulates typically have significant drug burst release, low drug loading and uncontrollable drug encapsulation efficiency. To address these issues, we developed nanoconjugation technique to allow successful formulations of sub-100 nm sized, mono-modal nanoparticles with definable drug loading, quantitative drug loading efficiency and controlled release profiles. Nanoconjugation has two steps. In the first step, hydroxyl-containing therapeutic agents are used as initiators to initiate living polymerization of cyclic ester monomers (e.g., lactide), and result in polyester-therapeutics conjugates. In the second step, precipitation of the polyester-therapeutics conjugates gives the desired polyester-drug conjugated nanoparticles, or called nanoconjugates. Using paclitaxel as a model drug, we have been able to formulate paclitaxel-polylactide nanoconjugates with 100% drug incorporation efficiency and up to 37% drug loading. The burst release of the incorporated drug from the resulting nanoconjugates is significantly eliminated. Toxicities of nanoconjugates can be precisely tuned by adjusting drug loading. This new type of nanoparticles is promising delivery vehicle for cancer therapy with improved efficacy and reduced toxicity.
3:00 PM - **FF2.2
Nanotechnology in Non-viral Drug Delivery for Cancer Therapy.
Huixin He 1
1 Chemistry, Rutgers University, Newark, New Jersey, United States
Show AbstractNanotechnology profoundly affects multiple facets of drug discovery, diagnosis and treatment of disease. The most important near-term contribution of nanotechnology to these areas will be in the form of extremely sensitive biosensors and efficient drug delivery system. We explore the novel properties of nanomaterials to develop extremely sensitive molecular detection and multifunctional drug delivery systems, which are hard to be realized by traditional technologies. In this presentation, novel applications of several engineered nanoparticles for non-viral drug delivery system will be discussed. Special efforts are paid in exploring the unique properties of engineered nanoparticles in developing multifunctional nanomedicine platforms which have the ability to in vivo co-deliver traditional anticancer drugs and novel short inference RNAs for efficient cancer therapy, and the ability to timely monitor the therapeutic outcomes of the delivered drugs.
3:30 PM - FF2.3
Template-fabricated Nanostructured Polymers for Drug Delivery.
Daniel Bernards 1 , Tejal Desai 1
1 , University of California, San Francisco, San Francisco, California, United States
Show AbstractIn the field of drug delivery, many therapeutic treatments are ideally administered to a patient at a constant rate over a certain time period. Yet, a considerable fraction of therapies exhibit an initial spike in therapeutic concentration that exceeds the useful amount and can sometimes have negative side-effects to patient health. By engineering drug delivery devices appropriately such undesired treatment effects can be avoided. Nanostructured scaffolds are a promising approach to achieving constant drug delivery over time. When a porous material is loaded with a therapeutic that is comparable to the pore size of the material, the diffusion of therapeutic out of the material is constrained. This type of constrained diffusion results in zero-order release of therapeutic and a constant rate of drug delivery over time. Given the size of most therapeutic molecules and proteins, materials must be structured at the nanometer scale to take advantage of this approach to drug delivery.The majority of existing nanoporous materials are fabricated from inorganic materials, owing to their crystallinity, knowledge of processing techniques, and chemical inertness. Unfortunately, these materials are not suitable for all applications, particularly those where invasiveness, long term biological viability, or device stiffness are a concern. Ideally, implantable drug delivery devices would exhibit long-term constant drug delivery without sacrificing flexibility and biodegradability. For this reason, a biodegradable polymer substrate is well suited for this application. Polymeric devices can be implanted or injected with minimal invasiveness, tailored to the stiffness of their environment, and selected to biodegrade such that removal is unnecessary after their therapeutic usefulness. In this work, we fabricate nanoporous polymer films using nanostructured inorganics as templates. A variety of templates and porous polymer films are characterized using scanning electron microscopy, and elution of prototypical small molecules and proteins from nanoporous polymers will be discussed.
3:45 PM - FF2.4
Drug Elution Kinetics from Nanoporous Templates.
Evin Gultepe 1 2 , Dattatri Nagesha 1 2 , Srinivas Sridhar 1 2
1 Physics, Northeastern University, Boston, Massachusetts, United States, 2 eMRI, Northeastern University, Boston, Massachusetts, United States
Show AbstractNanoporous templates have potential for use in the area of biomedical applications. Using controlled anodization, nanoporous surface can be achieved on metals such as aluminum and titanium. The pore size, pore density and pore thickness can be precisely controlled by varying the experimental conditions. We are using nanoporous alumina as a template for drug delivery applications e.g. for localized delivery from implant surfaces. A fluorescent model drug, Doxorubicin, is loaded into nanoporous templates to study release profile. The elution of these drug molecules was studied by using in-situ fluorescent measurements. A theoretical model of elution kinetics of drug molecules from nano-size pores was constructed based on the experimental results. The details of the model as well as the effect of pore dimensions such as different pore diameters and template thicknesses on elution kinetics will be discussed. This work was supported by the IGERT Nanomedicine Science and Technology (NSF-0504331).
4:30 PM - **FF2.5
Protein Delivery by Polysaccharide Nanogel for Cancer Immunotherapy.
Kazunari Akiyoshi 1
1 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo Japan
Show AbstractWe developed nanogels of hydrophobized polysaccharides such as cholesterol-bearing pullulan (CHP) which form relatively monodisperse and colloidally stable nanogel (-30 nm) in water. CHP nanogel trapped a chemotherapeutic agent as well as proteins [1]. It is noteworthy that CHP nanogel shows molecular chaperone-like activity. The nanogel allows the encapsulated protein to undergo refolding to gain the physiological bioactivities upon release from the nanogel [2]. The induction of a specific immune response against tumor cells is a highly achievable goal in immune therapy for cancer. We reported a novel nanogel/oncoprotein complex vaccine[3-5]. For example, nanogels of cholesteryl pullulan (CHP) complexed with HER2 soluble protein has been demonstrated in mice model to elicit efficient CD8+ and CD4+ T cell responses and to produce higher titers of antibodies against HER2 protein[3]. Clinical trial demonstrated that vaccination with the CHP-HER2 induced HER2-specific CD8+ and/or CD4+ T cell immune responses in five out of nine patients [4]. We reported polysaccharide nanogel delivery system for cytokine such as recombinant murine IL-12 (rmIL-12)[6]. For a valid cytokine immunotherapy of malignancies, a suitable delivery system that ensures slow-release of cytokines is required, because short half-life in vivo and causing severe systemic toxic effects. After subcutaneously injected into mice, the CHP/rmIL-12 complex led to a prolonged elevation in IL-12 concentration in the sera. Repetitive administrations of the CHP/rmIL-12, but not rmIL-12 alone, induced drastic growth retardation of preestablished subcutaneous fibrosarcoma without causing any serious toxic event. The present study proposes a novel therapeutic technology that is taking advantage of slow and sustained release of bioactive cytokines from the nanogels.References1) H. Ayame, et al., Bioconjugated Chem., 19, 882-890 (2008)2) X.G. Gu, et al., Cancer Res., 58 3385-3390 (1998)3) Y. Nomura, et al., FEBS Lett., 553, 271-276 (2003).4) S. Kitano, et al., Clinical Cancer Research, 12, 7397-7405 (2006)5) A. Uenaka, et al., Cancer Immunity, 7, 9-20 (2007)6) T. Shimizu, et al., BBRC., 367, 330-335 (2008)
5:00 PM - FF2.6
In vivo Toxicity Studies of New Drug Nanocarriers: Porous Iron Carboxylates.
Patricia Horcajada 1 2 , Ruxandra Gref 2 , Christian Serre 1 , Sophie Gil 1 , Phuong Bories 3 , Christian Bories 1 , Luc Cynober 3 , Gerard Ferey 1 , Patrick Couvreur 2
1 Institut Lavoisier, University of Versailles, Versailles France, 2 Faculty of Pharmacy, University Paris Sud, Chatenay Malabry France, 3 , Parvis Notre Dame Hospital , Paris France
Show AbstractThere is actually a strong effort devoted to the development of methods of controlling the drug release in order to meet the need for prolonged and better control of drug administration.[1] The various routes can be divided in two categories: the “organic route” (dendritic macromolecules or polymers) and the “inorganic route” (zeolites or mesoporous silicates materials). In the first case, a wide range of drugs can be encapsulated but a controlled release is difficult to achieve in the absence of well-defined porosity while in the second case, a controlled release is achieved by a grafting of organic molecules on the pore walls but with a decrease in the drug loading capacity.[2] An alternative route would be the use of porous hybrid inorganic-organic solids that combine a high and regular porosity and the presence of organic groups within the framework to achieve both a high drug loading and a controlled release. Thus, rigid porous carboxylates MIL-100/101 with very large pores have revealed a remarkable drug storage capacity (up to 1.4 g Ibuprofen/g MIL-101) and a complete drug controlled release under physiological conditions dependent on the interaction between the host and the guest, from three up to six days.[3] This concept has been recently extended to the flexible iron carboxylate MIL-53 which exhibit an unusual zero-order kinetics of release, totally predictable.[4] Moreover, exceptionally high loading capacities of antitumoral or retroviral drugs and controlled drug releases after 6 days under physiological conditions have been achieved using nanoparticles of these porous solids, which allow “furtivity” and targeting properties by their surface modification.[5] Nevertheless, the use of these solids as drug nanocarriers is conditioned to their toxicity. First experiments of the acute and subacute in vivo toxicity tests were performed by the i.v. administration of two porous iron (III) carboxylates (MIL-88A and MIL-88Bt) to groups of 4/8 Wistar female rats. The evaluation of the animal behavior, evolution of the animal and organs weights, the inflammatory process, enzymatic activity (cyp-450) as well as the evolution of the different serum parameters and organ histology have been determined. All results are in agreement with the absence of severe toxicity caused by the in vivo administration of iron carboxylates. 1. Langer R., J. Controled Release, 62, 7 (1999)2. Doadrio J.C., Sousa E.M.B., I. Izquierdo-Barba, Doadrio A.L., Perez-Pariente J., Valet-Regi M., J. Mater. Chem., 16, 462 (2006) 3. Horcajada P., Serre C., Vallet-Regí M., Sebban M., Taulelle F., Férey G., Angew. Chem. Int. Ed., 45, 5974 (2006)4. Horcajada, P., Serre C., Maurin G., Ramsahye N.A., Balas F., Vallet-Regí M., Sebban M., Taulelle F., Férey G., J. Am. Chem. Soc., 130, 6774 (2008)5. Horcajada P., Serre C., Gref R., Férey G., Couvreur P., FR 07/06873, 01 october 2007 and FR 07/06875, 01 october 2007
5:15 PM - FF2.7
Self-assembled Lipid-nanocrystal Vesicle Hybrids as Theranostic Devices for Cancer.
Wafa' Al-Jamal 1 , Khuloud Al-Jamal 1 , Kostas Kostarelos 1
1 Nanomedicine Lab, The School of Pharmacy, University of London, London United Kingdom
Show Abstract5:30 PM - FF2.8
Biodegradable Segmented Nanorods for Controlled Drug Delivery.
Shelley Dougherty 1 , Ryan Blair 1 , Jianyu Liang 1 , Timothy Kowalik 2
1 Material Science and Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, United States, 2 Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States
Show AbstractHeterogeneous, segmented one-dimensional (1D) nanomaterials, such as nanorods and nanowires, have been utilized for a variety of different biomedical applications because they offer a unique combination of properties and provide a material platform for integrating multiple functions. These multifunctional 1D nanomaterials are commonly fabricated from metals or semiconductors using a variety of techniques such as electrodeposition or chemical vapor deposition. Biomedical applications for these structures include biosensing, imaging, drug and gene delivery, and vaccine applications.We propose a template assisted wetting approach to fabricate segmented polymer nanorods using biodegradable polymers for controlled drug delivery. This project first studies the in vitro polymer degradation and drug release kinetics of homogeneous nanorods fabricated from individual polymers to understand the influence of the size and aspect ratio of 1D polymer nanorods. Based on this understanding, we design and fabricate heterogeneous segmented nanorods from two different alternating polymers for controlled drug release. Since the template-assisted fabrication approach provides us unprecedented control over the size, spacing, and length of the heterogeneous polymer nanorods, the effects of segment spacing, size of the nanorods, and aspect ratio on the drug release kinetics can be investigated.As a proof of concept, polystyrene and poly(methyl methacrylate) were used as model polymers to fabricate segmented structures. Anodized aluminum oxide membranes with an average pore size of 200 nm were wetted at 150C by multilayered thin films of PS and PMMA. We were able to fabricate segmented nanorods and unique core-shell morphology. Based on these results we have optimized conditions for segmented nanorods, and have selected polycaprolactone and poly(DL-lactide) for the fabrication of biodegradable segmented nanorods. The length and morphology of the nanorods is characterized using SEM and TEM. The degradation kinetics of these heterogeneous nanostructures is determined using GPC and the drug release from the polymer segments is monitored using UV-vis spectroscopy. Results obtained for the heterogenous segmented nanorods are compared with the homogenous, single polymer nanorods.
5:45 PM - FF2.9
Nanostructured Thin Films From Biodegradable Star Polymer Occlusion Complexes: A Versatile and Controlled Platform for Layered Surface Based Drug Delivery.
Joseph Sly 1 , Cecile Bonifacio 2 , Lilian Chang 2 , Eric Appel 1 , James Hedrick 1 , Melanie McNeil 2 , C. Jefferson 1 , William Risk 1 , Robert Miller 1
1 , IBM ARC, San Jose, California, United States, 2 Chemical and Materials Engineering, San Jose State University, San Jose, California, United States
Show AbstractThe use of thin film surface coatings as a platform for the slow and controlled delivery of hydrophobic therapeutics within the body is receiving increased attention. There currently remains, however, many significant problems with this approach, such as controlling the film structure, incorporation of the drug within the film and then controlling the release of the drug from the film. To address these key issues we are examining the combination of the “layer-by-layer” (LBL) self-assembly process with three dimensional, hyperbranched, star polymers as building blocks for nanostructured, composite, thin film formation. Using model star polymer materials and surface plasmon resonance (SPR) to monitor thin film formation, we have previously shown that successive layers of complimentary functionalised star polymers can be rapidly deposited (< 10 seconds) to form reproducible, uniform, and robust organic multilayer star polymer thin films. By atomic force microscopy (AFM), the star polymer thin films were characterized as being stable and contiguous surfaces in the dry state. These LBL techniques are currently being adapted for thin film formation with more structurally complex peripherally functionalized, core / shell (hydrophobic/hydrophilic), biodegradable, star polymers. These "unimolecular micelles" can be readily preloaded with hydrophobic "cargo" to form self-assembled, water soluble, macromolecular occlusion complexes prior to thin film deposition, thus forming a versatile and controlled composite building block for use in multilayered star polymer thin film formation. Polyethyleneoxide / polycaprolactone based star polymer occlusion complexes with hydrophobic materials (even large hydrophobic dyes porphyrins and phthalocyanines), proved to have long term stablity in neutral pH but slowly degrade under physiological conditions releasing their cargo to the environment over time. Investigations into both the formation and degradation / release profiles of multilayered thin film structures formed from these star polymer composite materials will be presented. The ability to preload the star polymer building blocks with different materials for sequential multilayer build up within the thin film structure will then be discussed as an avenue for the engineering of complimentary, sequential controlled drug delivery platforms.
FF3: Poster Session: Nanofunctional Material Characterization and Properties for Biomedical Applications
Session Chairs
Sangeeta Bhatia
Anja Boisen
Larry Nagahara
Thomas Thundat
Tuesday AM, December 02, 2008
Exhibition Hall D (Hynes)
9:00 PM - FF3.1
Characterization and Modeling of High Speed Relative Humidity Sensors.
Mike Taschuk 1 , Kathleen Krause 1 , Mike Brett 1 2
1 Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada, 2 , NRC National Institute for Nanotechnology, Edmonton, Alberta, Canada
Show AbstractOur group has been studying the relative humidity (RH) sensing properties of nanostructured thin films produced by glancing angle deposition (GLAD). Medical applications such as apnea [1] or neonatal respiration monitors [2] require response times below 1 s. We have demonstrated sensor response times below 200 ms with optical [3] and as low as 50 ms with capacitive sensors [4]. The response of our electrical RH sensors depend on the extremely large low frequency dielectric constant of water adsorbed to metal oxides, which results in a three order of magnitude change in capacitance as RH is increased from 0 to 100%. The response time of our sensors varies with the size and nature of pores in our sensors, which in turn relies on column properties such as diameter and surface roughness. The GLAD technique controls film nanostructure and porosity through substrate motion control and feedback from real-time measurement of deposition rates. GLAD films have extremely high surface areas, and can be made of any material compatible with physical vapour deposition processes. Through adjusting deposition parameters, it is possible to tune the optimum sensitivity range of our sensors, while maintaining the low response times required by medical applications. To better understand the physical limitations which govern the performance of our devices, we have developed a detailed model which predicts sensor response time.Constructing a model for our devices requires an understanding of the surface area and diffusivity of the films, the interaction between water vapour and TiO2, and the electromagnetic behaviour of IDE devices. In this paper we characterize the performance and response time of GLAD RH sensors as a function of film thickness and deposition angle. The microstructure is characterized in detail through adsorption porisometry and image analysis of column radius as a function of height and deposition angle. A 1D numerical model describing response time of our devices is developed, which includes diffusion, adsorption and interdigitated electrode physics. The modeling results are compared with our experimental data; the comparison indicates that the limiting factor in our device performance is adsorption. Possibilities for improving device response time are explored numerically.[1] T. Tatara and K. Tsuzaki, J. Clin. Monit. 13 (1997) pp. 5 – 9[2] H.B. Valman et al. Brit. Med. J. 286 (1983) pp. 1783 – 1784[3] J.J. Steele et al. Sen. Act. B 120 (2006) pp. 213 – 219[4] J.J. Steele et al. IEEE Sen J. 7 (2007) pp. 955 – 956
9:00 PM - FF3.10
Synthesis and Assessment of Manufactured Nanomaterials Cytotoxicity in Nerve Cell.
Kyung Mi Lee 1 , Miri Yu 1 , Sung Yang 1
1 Chemistry, Kyung Hee Univ., Yongin Korea (the Republic of)
Show Abstract9:00 PM - FF3.11
Multi-shaped Nanogold Prepared by Non-thermal Plasma in Aqueous Solution and the Biocompatibility.
Nagahiro Saito 1 , Yasuhiro Nakamura 1 , Osamu Takai 1
1 , Nagoya University, Nagoya Japan
Show Abstract9:00 PM - FF3.12
Nanoparticle Characterization for the Study of Interaction with Biological Systems.
Nam Woong Song 1 , Hyun Huh 1 , Mijin Kim 1 , Hyunung Yu 1 , Hyun Kyong Son 1 , Wan Soo Yun 1 , Tae Geol Lee 1 , Dae Won Moon 1
1 , Korea Research Institute of Standards and Science, Daejeon Korea (the Republic of)
Show AbstractThe environment, health and safety (EHS) issues of nanomaterials for risk assessment become more emphasized along with the development of nanomaterial industry. To understand the effect of nanomaterials on EHS, the interaction of nanomaterials on living bodies should be investigated. However, the lack of detailed information about nanomaterials often lead the experimental results to be inconsistent or debated. Thus the physical and chemical properties of nanomaterials should be identified prior and posterior to the interaction study of nanomaterials with biological systems using relavant measurement techniques. Here, we synthesized Au nanoparticles (NPs) having different surface ligands and characterized their properties such as size (hard sphere and hydrodynamic), size distribution, surface ligand (including identification and quantitation), surface plasmon band and zetapotential by using TEM, DLS (dynamic light scattering), FT-IR, UV/Vis, and SIMS (secondary ion mass spectroscopy). The ligand of Au NP could be identified by using FT-IR and mass spectrometry. The degree of ligand exchange from citrate to thiol compounds could be quantified based on the comparison of UV/Vis and FT-IR band absorption intensities. The short and long term stabilities of Au NPs in the absence of unbound ligands or in the presence of 10 % serum was monitored by using UV/Vis absorption spectroscopy to get information about the behavior of Au NPs in biological environments. The problems in the measurement of hydrodynamic radius and zetapotential of NPs smaller than 30 nm in diameter will be addressed and a new method to overcome the high uncertainties in those measurents will be proposed.
9:00 PM - FF3.13
Control and Characterization of Chemical Properties of Locally Anode-Oxidized Si Surfaces.
Yuta Kashiwase 1 , Toshio Ogino 1
1 Graduate School of Engineering, Yokohama National Univercity, Yokohama Japan
Show AbstractFor new biomedical applications of the Si technology, a technique to control biomolecule adsorption on a substrate surface is required. Biomolecules are generally adsorbed on the surface by hydrophobic and/or electrostatic interactions between the molecules and the surfaces. We focus on local anode oxidation by atomic force microscopy (AFM), in which metal or semiconductor surface layers are oxidized by applying a voltage between the sample surface and the conductive AFM tip. We previously oxidized Si surfaces covered with octadecyltrichlorosilane (OTS) films by the AFM anode oxidation and measured the frictional forces using the AFM in air. We found that the surface chemical properties, particularly hydrophilicity/hydrophobicity, can be controlled[1]. The surfaces oxidized below about 6 V were relatively hydrophilic, whereas that formed by the higher voltages were relatively hydrophobic. We speculated that the oxide surface is terminated with OH groups when the applied voltage is relatively low, and that the oxide surface is covered with Si-O-Si groups instead of the OH groups when the applied voltage is relatively high. In the biological applications, behaviors in liquid environment are more important because biointerfaces in many bio-devices are constructed in buffer solutions. In this report, we characterized properties of the anode-oxidized surfaces in buffer solutions. We measured the frictional properties on the oxidized Si surfaces covered with 3-aminopropyltriethoxysilane (APTES) films in air, and compared them with those in buffer solutions. The behavior of frictional forces on the locally oxidized surfaces in the buffer solution is different from that in air. For example, the frictional force on the hydrophilic surface is relatively large in air, but, on the other hand, relatively small in the buffer solution. This is due to the bound water on the oxidized surfaces which decreases the friction for sliding of the AFM tip in buffer solution. From the experimental results, we confirmed that the present anode oxidation technique can be used to locally form chemically different surfaces in buffer solution. Therefore, the present technique will be promising for new nano-scaled bio-devices.[1] Y. Kashiwase, T. Oya, and T. Ogino: Jpn. J. Appl. Phys. 47 (2008) in press.
9:00 PM - FF3.14
Magnetic Behavior in Ligand-capped Gold Nanoparticles. Role of Thiol, Amine and Alcohol Ligands.
Eider Goikolea 1 , Jose Garitaonandia 2 , Maite Insausti 1 , Izaskun Gil de Muro 1 , Teófilo Rojo 1
1 Química Inorgánica, U.P.V./E.H.U., Bilbao Spain, 2 Física Aplicada II, U.P.V./E.H.U., Bilbao, Bizkaia, Spain
Show AbstractNoble metal nanoparticles (NPs) remain the focus of numerous studies because of their-size dependent electronic, optical, catalytic and magnetic properties. Furthermore, since magnetism was reported in dodecanethiol capped Au, Ag and Cu NPs [1], the interest in this kind of systems has increased considerably. This ferromagnetic like behavior has been attributed to the appearance of localized holes in the 5d shell resulting from a charge transfer from metal (M) surface atoms to S atoms of the ligand when forming M-S bonds.In order to study this ligand-metal interaction, here we present magnetic and spectroscopic properties of nanometer-size dodecanethiol (-SR), dodecaneamine (-NR) and dodecanol (-OR) capped Au NPs. The two-phase arrested-precipitation method described by Brust et al [2] was used to synthesize these capped NPs. In this procedure, AuCl4- anions are transferred from an aqueous solution to an organic phase by using tretraoctilammoniun bromide as the transfer agent and, subsequently, they are reduced with sodium borohydride solution in the presence of the desired organic ligand. The microstructural study of the samples was carried out by means of TEM microscopy. In all micrographs spheric NPs can be observed, being the mean size 2 nm for Au-SR particles and 8 nm for Au-OR and Au-NR ones. M vs. H measurements were performed at 5 and 300 K, and only thiol capped NPs showed hysteresis at both temperatures. This magnetic behavior indicates that the magnetic transition temperature is well above room temperature.Preliminary X-ray absorption analysis (EXAFS and XANES) were performed at the Au L3-edge at BM25 line from ESRF (Grenoble, France) for the different NPs. The XANES region of Au-SR nanoparticles showed a higher Au-ligand charge-transfer compared to bulk Au, and even to Au-OR or Au-NR NPs. In fact, in -OR and -NR capped nanoparticles the 5d hole-density is very similar to that of bulk Au.Finally, the UV-vis spectra allow us to demonstrate the character of the superficial electronic charge. In some samples, a band centered at 520 nm and associated to a plasmonic resonance characteristic of non localized electrons was observed. However, the lack of this band in the case of Au-SR NPs, evidences that Au-thiol interaction boosts the localization of 5d electrons. References:[1] P. Crespo et al, Phys. Rev. Lett. 93(8), 87204 (2004); J.S. Garitaonandia et al, Nanoletters, 8(2), 661 (2008).[2] M. Brust et al, J. Chem. Soc., Chem. Commun. 801 (1994).
9:00 PM - FF3.15
Study of Protein Adsorption onto a Polymer Film by in-situ UV Attenuated Total Reflectance Spectroscopy.
Maria-Antoaneta Bratescu 1 , Syohei Fujita 2 , Nagahiro Saito 3 , Osamu Takai 1
1 Ecotopia Science Institute, Nagoya University, Nagoya Japan, 2 Department of Materials, Physics and Energy Engineering, Nagoya University, Nagoya Japan, 3 Department of Molecular Design and Engineering, Nagoya University, Nagoya Japan
Show AbstractRecently graft chains polymer films and densely packed or charged polymer brushes were used to control the adsorption process of a protein on a surface.Our work presents experimental results on a protein adsorption onto a poly(acrylic acid) (PAA) film prepared by the graft polymerization method. The adsorption kinetics of human plasma fibrinogen (HPF) and bovine serum albumin (BSA) proteins were studied by in-situ UV attenuated total reflectance (ATR) spectroscopy method. Surface grafting polymerization of various substrates (polymers, silica, and metals) is mostly used to improve surface properties such as wettability, the antistatic property and the adsorption of biomolecules without deterioration of the bulk characteristics. In our experiment, the PAA polymer film was prepared by acrylic acid grafting in vapour phase onto a fused quartz substrate. The grafting polymerization device is equipped with an argon MW plasma system (100 Pa, 100 W), which permits to activate and clean the substrate surface before polymer deposition. Immediately after plasma treatment, the argon flow was cut off and the monomer vapour was introduced in the chamber at 2000 Pa pressure. The polymer film prepared by the grafting of acrylic acid in vapour phase onto the fused quartz substrate was characterized by atomic force microscopy (AFM), water contact angle and Fourier transform infrared (FTIR) spectroscopy measurements.The protein adsorption kinetics was determined by UV ATR spectroscopy. Experiments were performed using a custom-made apparatus, combining the fused quartz internal reflection element as the UV ATR sensor and a flow cell transparent to the light source. HPF and BSA protein concentrations varied from 0.1 to 10 μM. The typical absorption band of a protein is around 280 nm due to tryptophan and tyrosine amino acid residues. From time-resolved spectra at different protein concentrations the adsorption-desorption kinetics curves were obtained. The value of the free energy of the protein adsorption onto the PAA film was compared with the value of the free energy of the protein adsorption onto a non-deposited quatz surface.Ex-situ measurements of the PAA film covered with the protein adsorbed on surface were performed by AFM.
9:00 PM - FF3.16
Photo-resistivity of Functionalized Carbon Nanotube Networks.
Jeffrey Alston 1 , Jordan Poler 2
1 Chemistry, UNC-Charlotte, Charlotte, North Carolina, United States, 2 Chemistry, UNC-Charlotte, Charlotte, North Carolina, United States
Show AbstractWe use an established process to deposit randomly aligned straight lying, interpenetrated thin films of single walled carbon nanotubes (SWCNTs). With this method we produce a conductive optically transparent thin film with similar optical transmittance to indium tin oxide within the visible spectrum. The binding of optically and electrochemically active ruthenium coordination complexes to our carbon nanotube films yields an enhanced photoconductive response. Modulation of the photoconductive response can occur through the electron transfer from the complex through the ligand to the electron accepting CNT film. In this study we compare the behavior of our randomly aligned CNT thin films to that of molecularly combed CNT films and vertically aligned single walled carbon nanotube films grown by CVD method. Both film growth methods produce CNT films whose thickness can be controlled, and we present studies regarding dependence on this factor. These results suggest progress toward novel supramolecular control over carbon nanotube based sensors such as a biosensing technique involving ruthenium complexes as optically modulated sensors for the analysis of glucose. Absorbance, SEM, AFM and photo-resistivity data will be presented.
9:00 PM - FF3.17
Bacterial Colonization Analysis on Microcrystalline Diamond and Nanocomposite Carbon Films.
Javier Avalos 1 2 , T. Merced 3 , S. Rodriguez 2 , A. Ortiz-Vargas 1 , O. Medina 2 , J. Nocua 2 , M. Arvelo 2 , B. Weiner 1 4 , G. Morell 1 2
1 , Institute for Functional Nanomaterials, University of Puerto Rico, San Juan, Puerto Rico, United States, 2 , Department of Physics, University of Puerto Rico, San Juan, Puerto Rico, United States, 3 , Universidad Metropolitana de Puerto Rico, San Juan, Puerto Rico, United States, 4 , Department of Chemistry, University of Puerto Rico, San Juan, Puerto Rico, United States
Show AbstractThe medical implant and surgery tools technologies have experienced remarkable improvements due to the development of new materials. However, relatively little attention is devoted to problems associated with possible bacterial colonization on the implants’ and tools’ surfaces. The medical industry can greatly benefit from coatings designed to reduce the bacterial viability on implants and medical tools. We studied the settlement and growth of Escherichia coli and Corynebacterium xerosis bacteria on microcrystalline diamond and nanocomposite carbon films grown by hot filament chemical vapor deposition. The results indicate that they exhibit resistance to C. xerosis and E. coli bacterial colonization with respect to Stainless Steel and other materials. Possible mechanisms for this result will be discussed.
9:00 PM - FF3.18
Distance Dependence of the Phenyl Group from CdSe Quantum Dot Surface for Optical Detection of Aromatic Hydrocarbons.
Hasti Amiri 1 , Zhouying Zhao 1 , Teresa Dansereau 2 , Subhendu Panda 2 , Marina Petrukhina 2 , Michael Carpenter 1
1 College of Nanoscale Science and Engineering, University at Albany, Albany, New York, United States, 2 Chemistry, University at Albany, Albany, New York, United States
Show AbstractThe impact of hydrocarbon pollution on human health and the detection of over 200 organic compounds within human breath emissions at ppt to ppm levels, highlight the need for fast, sensitive and selective hydrocarbon detection systems for environmental impact studies as well as for the early detection of diseases. The hydrocarbon sensing properties of tailored CdSe semiconductor quantum dots (QDs) are currently being studied to determine their dependence on the phenyl group distance from the QD surface. The sensing characteristics of QDs with trioctyl phosphine oxide and stearic acid as stabilizing agents plus benzoic, phenylacetic, phenylbutanoic or phenylhexanoic acids as a surface enhancement agent were compared. QDs of the same size and with similar surface coverages, as determined by nuclear magnetic resonance technique, were coated onto a porous anodic aluminum oxide substrate by drop coating QD solutions. Initial results indicate that photoluminescence (PL) enhancement was observed more strongly for QDs with longer chain surface enhancement agents compared to those with shorter length upon film exposure to xylene vapor over the range of 15 to 9400 ppm in a balance of air. Detailed PL studies are underway which will measure calibration curves for the detection of xylene and toluene between 15 and 9400 ppm as a function of the phenyl group to QD surface distance.
9:00 PM - FF3.19
Polymer-Matrix Dependent Blinking Kinetics of Single CdSe/ZnS Nanocrystals by Photon-Counting Statistics.
Sang Yun Lee 1 , Tomohiro Hayashi 1 2 , Masahiko Hara 1 2
1 Department of Electronic Chemistry, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan, 2 Advanced Science Institute, RIKEN (The Institute of Physical and Chemical Research), Wako, Saitama, Japan
Show AbstractOver the recent decade, semiconductor nanocrystals (NCs) have attracted extensive attentions in fields of nano-science and technology owing to their optical properties, which can be tuned by their sizes and physicochemical surroundings. Despite the theoretically predicted exponential distribution, fluorescence intermittency (or blinking) of single semiconductor NCs has been described by power-law distribution. Recently, we have found that the blinking kinetics of single CdSe/ZnS NCs can be interpreted in terms of photon interval at high temporal resolutions of decimal μs, and our measurements have demonstrated that the blinking kinetics is obedient to single exponential distributions for “on” and “off” durations, which can be attributed to numerous short-term events resolved from the conventional long-term “on” and “off” states. In this study, we employ the single photon regime to elucidate blinking kinetics dependent on polymer matrix as a surrounding. Poly(N-vinylcarbazole) (PVK) and poly(methyl methacrylate) (PMMA) served as the polymer matrices. The time constant of the single exponential function for “off”-length was obviously shorten in PVK matrix compared with PMMA, while the time constants of “on”-lengths were quantitatively identical for both polymer matrices. On the basis of neutral-“on” and charged-“off” model, these findings suggest that electronic property of a polymer can regulate recovery times (or “off” lengths) of charged single NCs to their neutral states, where electron is known to serve as a carrier.
9:00 PM - FF3.2
An In vivo Study of the Biocompatibility of Classic and Novel Materials on Central Nervous System for Biomedical Applications.
Claudine Jaboro 1 , Heather Hanni 1 2 , Joseph Smolinski 1 , John Cavanaugh 3 , Gregory Auner 1 3
1 Electrical & Computer Engineering, Wayne State University, Detroit, Michigan, United States, 2 Biomedical Engineering, Lawrence Technological University, Southfield, Michigan, United States, 3 Biomedical Engineering, Wayne State University, Detroit, Michigan, United States
Show AbstractAn evaluation of the biocompatibility of classic and novel biomaterials is essential to the development of electrical stimulation and chemical drug delivery devices for chronic biomedical applications for the central nervous system. In evaluating biocompatibility, the material and the tissue should be analyzed to determine their interaction during in vivo neural exposure. The materials examined were sapphire and aluminum nitride (AlN) deposited on a sapphire substrate using plasma source molecular beam epitaxy (PSMBE). Borosilicate glass (BSG) was used as a control material. The implants measured 2.5mm (+/- .05mm) in diameter and 250µm (+/- 50µm) thick. The implants were exposed to neural tissue using a rat animal model for 10, 28 and 90 days. The implants were placed on the surface of the cerebral cortex directly below the dura mater. Before implantation analysis of the surface of each sample was performed using optical microscopy, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) was also conducted on one representative sample. During the period of implantation MR imaging was performed before implantation and at 10 and 28 days to determine in vivo activity. After the samples were removed, a series of surface analyses was performed to determine device surface/tissue interaction down to the atomic level. The characterization techniques used to explore mechanical and chemical changes on the surface or underlying material included optical microscopy, atomic force microscopy (AFM) and x-ray photoelectron spectroscopy (XPS). Representative materials were soaked in an enzyme solution after neural exposure to remove the tissue adhesions on the surface and determine any surface changes and/or invasive growth. Histology was performed on the underlying neural tissue using nissl, silver, glial fibrillary acidic protein (GFAP) and microglial staining. The results suggest that AlN is a bioactive material, encouraging adhesion to the material and promoting growth of the tissue. This may be directly associated with structure and topography. The characterization and histological data show that surface features such as roughness may have a direct effect on the neural biocompatibility of these chronic implants.
9:00 PM - FF3.20
A Study on the Characterization and Stability of Chitosan Coated Liposome DDS.
Min-Jung Kim 1 , Guk-Hwan An 1 , Hak-Kyong Kim 1 , Eun-kyu Lee 1 , Hee-Taik Kim 1 , Yong-Ho Choa 1
1 Fine Chemical Engineering, Hanyang University , Ansan, kyeonggi-Do, Korea (the Republic of)
Show Abstract Nanoliposomes are important carriers capable of packaging drugs for various delivery applications through passive targeting tumor sites by enhanced permeability and retention effect. Radiolabeled liposomes have potential applications in radiotherapy and diagnostic imaging. However, the physico-chemical instability of liposomes during manufacturing and storage limits their extensive application. Therefore, considerable studies have been made on the stability of liposomes over the last few years in order to overcome the problem of liposome. In this study, we attempted to prepare polymer coated liposomes using water-soluble chitosan in order to enhance the stability of Rhenium chloride-incorporated liposomes. They were characterized by particle size analyzer, fourier transform infrared spectroscopy(FT-IR), UV-vis spectrometer, dispersion stability analyzer(DSA), polarized optical microscopy, respectively. The chitosan coated liposomes are spherical and the particle size is several 100nm to 300nm. Incorporation of chitosan into the liposome bilayer decreased Rhenium chloride release out from the liposome due to increased rigidity of liposome membrane structure. Chitosan coated liposomes showed higher stability compared to non-coated liposome. The release characteristics of Rhenium chloride, encapsulated in liposome, were taken as a measure of stability of liposome membrane.
9:00 PM - FF3.21
Characterization of Neuron and Semiconductor Nanowire Interfaces.
Ki-Young Lee 1 , So-Jung Shim 1 , Il-Soo Kim 1 , Hwangyou Oh 1 , Sun-Oh Kim 2 , Hye Whon Rhim 2 , Seung-Han Park 3 , Heon-Jin Choi 1
1 Department of Materials Science and Engineering, Yonsei university, Seoul Korea (the Republic of), 2 Center for Chemoinformatics Research, Korea Institute of Science and Technology, Seoul Korea (the Republic of), 3 Department of Physics, Yonsei University, Seoul Korea (the Republic of)
Show AbstractThe neuron-semiconductor hybrid devices are powerful systems that allow to obtaining integrated information by non-invasive and long-term recording or stimulation of individual living neuron cell. Meanwhile, nanowires (NWs) are the unique material, which has a diameter on a nanometer scale, high aspect ratio (<103) and single crystallinity. Such properties make them the most suitable materials for the constructional units of neurodevice required the submicron sensing dimension and high electrical sensitivity. If the NW based neuron devices are constructed, the signal transfer from the neuron cells to NW or vice versa should be primarily dependent on the interfaces between the neuron cells and NWs. A study on the interfaces is thus crucial for understanding the signals from the neurodevices. Herein, we report the biocompatibility and the structure of interface between neuron cells and NWs. Si, SiGe, Ge, GaN and ZnO NWs were dispersed in ethanol by ultrasonicator and the dispersed solutions were laid down on the Si wafer. After sterilization by ethanol and UV light, the surfaces of nanowires were chemically modified by poly-L-lysine (PLL) coating for increment of cell adhesion. Hippocampal neurons, which have an important role in the formation of new memories about experienced events and used in storing and processing spatial information, were then cultured on the nanowires under a humidified atmosphere of 95% air and 5% CO2 at 37 °C. The 4~5 day cultured neuron cells were treated by a critical point drying technique, glutaraldehyde for fixation and osmium tetroxide for contrast enhancement, and then observed by scanning electron microscopy (SEM). Except ZnO NWs, hippocampal neurons were well grown with many stuck out processes. Viability of the hippocampal neurons and stability of NWs in culture media was studied via MTT assay and inductively coupled plasma. It revealed that the hippocampal neurons cultured with Si and SiGe NWs survived with the highest ratio. Using above fixed SiNW and hippocampal neuron, cross-section samples were prepared by focused ion beam and observed by transmission electronmicroscopy (TEM). The results showed that the cells were adhered well on the NWs. It also showed that the interfaces were consisted with several nanometers of SiO2, which is the products of natural oxidation of NWs, and PPL layers. Based on these outcomes, the biocompatible of NWs to neuron cells and the feasibility of signal transfer from cultured neuron cells to NWs or vice versa will be discussed.
9:00 PM - FF3.23
Highly Reproducible Single Polymer and Metal Nanowires using Electrophoresis Method.
Innam Lee 1 , Yushi Hu 1 , Minhee Yun 1
1 Electrical and Computer Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Show AbstractConventional nanowire synthesis such as solution-liquid-solid growth method or laser ablation method yield bundles of nanowires. Utilization of a nanowire from those methods requires many post-processes in order to build an electric device structure. While processing the nanowire utilization, it is important to keep high performance, cost efficiency, and reliability in mind. Additionally, the reproducibility of nanowire fabrication is a very important issue in the performance of an electric device based on a nanowire. Here, we report a reproducible single and site-specific nanowire fabrication through an electrophoresis growth method. Single metallic or conducting polymer nanowires are electrodeposited inside a 100nm width nanochannel from electrolyte solution and aligned with electrodes on both ends of the nanochannel. This method greatly simplifies the process of building up an electric device with a single nanowire by eliminating troublesome steps such as nanowire positioning and alignment with electrodes. In the electrophoresis growth method, pre-built electrode and nanochannel arrays help increase the density of nanowire in an electric device. Our electrophoresis growth method with acetone wetting improves the uniformity, reliability, reproducibility, addressability and cost efficiency in nanowire synthesis.For characterization of fabricated single nanowires, the I-V curves of single polyaniline (PANI) and Palladium (Pd) nanowire were measured by using a semiconductor analyzer. PANI nanowire resistance changed significantly before acetone wetting and after acetone wetting. Scanning electron microscope (SEM) and atomic force microscope (AFM) images of nanowires were studied to examine nanowire morphology and topology. Those measurements proved that nanowire structures and electrical conductivities were improved by acetone wetting for PANI nanowires and had good reproducibility after electrophoresis growth. The resistances of PANI nanowires fabricated in this work were found to be 297.75 ± 31.7Ω. The dimensions of PANI nanowire were 133.77±13.82 nm in thickness, 133.17±13.01 nm in width, and 1 μm to 5.5 μm in length. Additionally, Pd metallic nanowires with sub-100nm width and resistance from 100 ohms to 100k ohms were fabricated. During the SEM analysis of Pd nanowires, we found three different structures. The structures of the Pd nanowires were controlled by current change. Hydrogen sensors based on Pd single nanowires were demonstrated in order to test a feasibility of the fabricated nanowires in this research . The Pd nanowire hydrogen sensor features small size, low power consumption (~nW) and shows extremely high sensitivity in the range of 20,000 ppm to 5 ppm. Different sensing behaviors are discussed for three different nanowire structures and possible mechanisms are proposed in this research.
9:00 PM - FF3.24
Surface Chemistry Control of Aligned Carbon Nanotube Arrays.
Yu Mao 1 , Yumin Ye 1
1 Dept. of Biosystens Engineering , Oklahoma State University, Stillwater, Oklahoma, United States
Show Abstract9:00 PM - FF3.26
Immunostimulatory CpG Sequence to Enhance Cytokine Secretion Owing to the Cluster Effect and its Receptor Specific DDS to APCs.
Kazuo Sakurai 1
1 Chemistry and Biochemistry, The University of Kitakyushu, Kitakyushu Japan
Show AbstractBacterial DNA shows potent immunostimulatory activity as administrated into vertebrates. The cause of this incident resides in unmethylated CG rich domain that emerges nearly 20 times more frequently in bacterial than vertebrate DNA. Synthetic oligodeoxynucleotides containing CG pair (CpG ODN) can induce the similar stimulatory effect as bacterial DNA. CpG ODN is recognized by a pattern recognition receptor called Toll-like receptor 9 (TLR9) in antigen-presenting cells (APCs). A Recent study showed that dimerization of TLR9 is necessary to invoke the subsequent biological events, suggesting that allosterically-regulated immunostimulation can be achieved by designing CpG DNA higher-order architecture. The present paper reviews our recent finding of the cluster effect of CpG ODN and its receptor-mediated specific delivery by use of decint-1 recognizing b-1,3-glucans that can be used for ODN delivery.A natural polysaccharide called schizophyllan (SPG) forms a complex with polynucleotides, where SPG is composed of b-(1→3)-D-glucan main chain and one b-(1→6)- D-glycosyl side chain links to the main chain at every three glucose residues. We have previously reported that the complex can deliver the bound CpG ODN to APCs with protecting the ODN against DNase-mediated degradation. Various advantages of the complex in ODN delivery have been demonstrated in vitro as well as in vivo. Among others, SPG and other b-(1→3)-D-glucans can be recognized by a receptor called dectin-1 that antigen presenting cells (APCs) have on their cellular surface and ODNs are specifically ingested by APCs. The ingested ODN can exert their biological functions.
9:00 PM - FF3.27
TEM Analysis of Magnetite Nanoparticles for Biomedical Applications.
Stefan Gustafsson 1 , Andrea Fornara 2 , Christer Johansson 3 , Hannes Lichte 4 , Mamoun Muhammed 2 , Karolina Petersson 3 , Daniel Wolf 4 , Fei Ye 2 , Eva Olsson 1
1 Applied Physics, Chalmers University of Technology, Gothenburg Sweden, 2 Division of Functional materials, Royal Institute of Technology, Stockholm Sweden, 3 , Imego AB, Gothenburg Sweden, 4 , Triebenberg Lab, Dresden Germany
Show AbstractMagnetic nanoparticles (MNP) have attracted a lot of attention in recent years due to their potential use within the fields of biotechnology and biomedicine. MNP may be used as contrast agents in magnetic resonance imaging (MRI), carriers for drug delivery or immobilization substrates for biosensor applications. Depending on the application, certain requirements regarding size, shape, monodispersity, chemistry and crystallinity need to be imposed on the particle population. It is thus of special importance to have a precise control of the particle microstructure and properties during synthesis. In this work, the structure and properties of MNP of magnetite (Fe3O4), aimed for immunoassay applications, are investigated in the transmission electron microscope (TEM). The analysis was performed using a Philips CM200 TEM equipped with a Link ISIS EDX system and a Gatan Imaging filter (GIF). The magnetite nanoparticles were synthesized through hydrolysis of chelate metal alkoxide complexes. The evolution of the particle size distribution was monitored by looking at samples taken from the reaction mixture at different times during synthesis. The changes in the size distribution and in the particle microstructure revealed that coarsening mechanisms are active during particle growth. Most particles are defect free single crystals. There are, however, also polycrystalline particles with defect structures, most commonly stacking faults and twin boundaries, present in the reaction solution at all times. The mean size of the fully synthesized particles is 20 nm which is just above the superparamagnetic limit for magnetite, implying that the single crystals consist of one single magnetic domain. Electron holography in the TEM reveals a slight phase shift due to the magnetic field of the particles. Structural analysis by means of diffraction and chemical analysis using electron energy loss spectroscopy (EELS) confirmed the magnetite structure and composition. The EELS investigation revealed the difference between different iron oxide phases and showed that the particles are not oxidized to maghemite or haematite which would degrade their magnetic properties. The particle structure and chemistry have been found to be well suited for biosensor applications using Brownian motion relaxation measurements.
9:00 PM - FF3.28
Quantum Dot-molecule Energy Transfer Systems Applicable to Multiphoton-excited Sensing and Imaging of Biochemical Parameters.
Andrew Greytak 1 , Rebecca Somers 1 , Emily McLaurin 1 , Wenhao Liu 1 , Moungi Bawendi 1 , Daniel Nocera 1
1 Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Show Abstract9:00 PM - FF3.29
Bioconjugated Nanoparticle Disease Therapy Concept.
Maurice Bianchi 1
1 Special Projects, The Boeing Company, Palos Verdes Estates, California, United States
Show AbstractThe concept uses nanoparticles or quantum dots that possess a bandgap that when an electron hole pair is generated by irradiating with photons above their bandgap would emit photons with a wavelength in the far ultraviolet (UV) region from about 300 down to 180 nanometers. This is the so-called germicidal ultraviolet light regime whose peak is centered at about 270 nm where all organisms (viruses, bacteria, parasites and molds) or cells that contain DNA or RNA are susceptible to mitigation. It has been shown by Shreier, et al (Thymine Dimerization in DNA is an Utrafast Photoreaction, Science, Vol 315, 2 Feb. 2007, pgs 625-629) that when DNA, for example, is irradiated with UV light of 272 nm in wavelength the chemical bonds of the thymine base pairs of the DNA helix are broken and the ends dimerize to open up the helix thereby preventing it from acting as a template for the production of another cell or organism resulting in apoptosis. By using femto-second time resolved infrared spectroscopy they found that the dimers are fully formed in about 1 picosecond. In this therapy concept the nanoparticle or quantum dot would first be made biocompatible with a coating such as dextrin to make it compatible with the body. Then an appropriate ligand, conjugate or monoclonal antibody would be attached to the particle that would be specific for attaching to the target organism or cell. In the case of cancer cells most have surface specific antigens that are unique to the cancer cell and not to normal cells for others, such as leukemic cancers, other ligands are available for conjugation. Monoclonal antibodies and other ligands have and can be made to bind to these sites and not to normal cells. The treatment then would entail injecting these bioconjugated nanoparticles that possess the appropriate bandgap into the patient. The particles that did not attach would be excreted through the patient’s renal system. After an appropriate interval the patient would be irradiated with x-rays in the KeV range. The particles would then emit large quantities of UV photons for every KeV absorbed x-ray photon through the process of multi-exciton generation. The absorbed photons would disrupt the cell or organism’s DNA or RNA that it was attached to leading to apoptosis of the cell or organism. The concept was been considered for the 2007 Gotham and Ira Sohn Prizes for Cancer Research.U.S. and international patents have been applied for on the concept and, currently, two cancer researchers are in the process of being licensed to carry out research and development on the concept for the treatment of cancer.
9:00 PM - FF3.3
Biological Responses of Silicon Nanoparticles.
Jonghoon Choi 1 2 3 , Qin Zhang 3 , Vytas Reipa 2 , Nam Sun Wang 1 , Melvin Stratmeyer 3 , Victoria Hitchins 3 , Peter Goering 3
1 Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, United States, 2 Biochemical science, NIST, Gaithersburg, Maryland, United States, 3 CDRH, FDA, Silver Spring, Maryland, United States
Show AbstractPhotoluminescent silicon nanoparticles have a bright and stable fluorescence and are promising candidates for use in bio-imaging, cell staining and drug delivery. Biocompatibility of photoluminescent silicon nanoparticles was tested using standard protocols of measuring cytotoxicity and inflammatory responses for micron sized particles with murine macrophage cell line RAW 264.7. The biological responses of silicon nanoparticles (SNs, 3.0 ± 1.0 nm) and silicon microparticles (SMs, 100~3000 nm) were compared in murine macrophage cells. Dry-heat sterilized nano and micro particles were incubated in macrophage cell cultures with and without added lipopolysaccharide (LPS). Cells were examined for gross morphological appearance under with phase contrast microscopy. Cytotoxicity was detected with trypan blue dye exclusion and MTT assays. The supernatants were assayed for production of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and nitric oxide (NO) by macrophages. Silicon nanoparticles at concentrations up to 20 μg/ml exhibited no statistically significant cytotoxicity or inflammatory responses in RAW cells. However, nano and micro particles at concentrations higher than 20 and 200 μg/ml, respectively, showed a statistically significant increase in cytotoxicity compared to lower concentrations. The amounts of TNF-α, and IL-6 produced by macrophages decreased with increasing concentrations of SNs but increased with greater SMs, while the amount of nitric oxide remained unchanged. Fluorescence microscopy showed that Si nanoparticles were associated with macrophage cells. The present study of murine macrophages, exposed to dry-heat sterilized silicon nanoparticles will help define safety requirements for nanoparticles in biomedical applications.
9:00 PM - FF3.30
DC and AC Measurements of Magnetite Nanoparticulates and Implications for Nonlinear Response.
Ricky Moore 1 , Silvia Liong 1
1 Georgia Tech Research Institute, Georgia Tech, Atlanta Ga, Georgia, United States
Show AbstractNonlinear response of nanoparticles has been measured on nano ferri magnetic particulates and modeled using analytical and numerical micromagnetic solvers [Science Digest Sensors-Actuators B, 121 (2007) p. 330; APL 93, 10, p. 8752]. Saturation magnetization, coercivity and nonlinear data are important for nanoparticle applications as bio contrast agents, identifiers or treatments. At diameters less than ~ 100 nm properties deviate from bulk and nonlinear response is scale dependent. In preparation for future nonlinear magnetic characterizations we describe in this paper preparation, characterization and measurement of linear DC and AC magnetic properties of magnetite (Fe3O4) nanoparticles (size ranges of 7-50 nm) and polymer composites of those particulates. The nanoparticles were synthesized by chemical coprecipitation, a method that allowed for the production of relatively large quantities (on the order of grams). Ferric and ferrous salts, FeCl3 and FeCl2 respectively, were used as precursors and NaOH was the precipitating agent. In basic conditions, ferric and ferrous ions hydrolyzed and precipitated as iron oxide particles. Variations in pH, temperature, iron salt concentration, and ionic strength were used to control the size and morphology of the particles. Particle size was calculated from XRD data and supported by TEM images. Vibrating sample magnetometry was used to measure the room-temperature DC magnetization and coercivity of the particulates. Strip line cavity and coaxial line reflection-transmission were used to measure AC permeability of Fe3O4 – polymer composites from 1 Megahertz to 10 Gigahertz. DC saturation magnetization and coercivity were found to decrease with particle dimension. Measured magnetization data fitted a model that calculates the magnetization as a volumetric average of a spherical core with magnetization near the bulk value and a passive outer shell. This analysis is supported by measurements on other iron-oxide nanoparticle systems found in the literature. The thickness of the shell calculated from the magnetization data (0.84 nm) is approximately equal to the lattice constant of the nanoparticles (0.8397 nm) measured by XRD. Composites contained particulate fractions less than 20% by volume. Therefore applications of effective media were justified for calculation of AC permeability of isolate particulates. Permeability decreased with particulate size. AC permeability measurements (1 Megahertz to 10 Gigahertz) found similar trends and these data are fit to Lorentz relaxations to determine magnetization, anisotropy and relaxation as function of size and composite volume fraction.
9:00 PM - FF3.32
Mimicking Proteins Interfacial Energy in Liquid using Controlled Functionalization of Gold Nanoparticles.
Kislon Voitchovsky 1 , Jeffrey Kuna 1 , Francesco Stellacci 1
1 DMSE, MIT, Cambridge, Massachusetts, United States
Show AbstractProteins are highly optimized biological nano-machines that can carry out specific tasks in a particular environment. This is achieved by a complex combination of molecular interactions which largely depend on the surrounding medium, typically an aqueous solution. Understanding how proteins control and structure the liquid at their surface can therefore provide important new insight into fundamental biological processes such as protein folding and dynamics and open new avenues in bio-medical and pharmaceutical research. Here we use atomic force microscopy (AFM) in water to study gold nanoparticles functionalized in a controlled fashion with a mixture of hydrophobic and hydrophilic ligands. We present simultaneous topographic and quantitative water-surface energy mapping with sub-nanometer resolution. The surface of the functionlized nanoporaticles exhibit alternate hydrophobic and hydrophilic domains which size corresponds to what can typically be found on protein surfaces. Comparison of our AFM results with contact angle measurements show that the nanoparticules can modulate their interfacial energy in a non-linear fashion with the ligands domains' size. The results can not be explained by standard continuum thermodynamics and require taking into account the size, nature and orientation of the water molecules at the interface. We believe our finding provides important new insight in our current understanding of systems involving nano-structured surface in a liquid and opens new possiblities for bio-medical applications.
9:00 PM - FF3.33
The Effect of Gold Nanorods on Tissue Remodeling.
Patrick Sisco 1 , Christopher Wilson 3 , Ekaternia Mironova 3 , Sarah Baxter 2 , Catherine Murphy 1 , Edie Goldsmith 3
1 Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, United States, 3 Cell and Developmental Biology and Anatomy, University of South Carolina, Columbia, South Carolina, United States, 2 Mechanical Engineering, University of South Carolina, Columbia, South Carolina, United States
Show Abstract Cell behavior in the presence of nanomaterials is typically explored through simple viability assays, but there is mounting evidence that nanomaterials can have more subtle effects on a variety of cell functions. Numerous studies have documented the cellular uptake and cytotoxicity of gold nanoparticles in different cell types, but very little is known about how nanoparticles affect cellular function. In this work, we examine how cardiac fibroblast-mediated extracellular matrix remodeling is perturbed by gold nanoparticles. To investigate the capacity for nanomaterials to modulate this process, 3-D collagen gel constructs were prepared from neonatal cardiac fibroblasts and type I collagen with and without gold nanorods (392 nm long x 22 nm wide, overcoated with polystyrene sulfonate). Over a 24h period the collagen-nanomaterial composite scaffolds showed significantly less contraction than controls, and the reduced contraction was not due to cell death or differences in gelatinase activity. Cardiac fibroblasts suspended in the composite scaffolds exhibited a different phenotype than cells in control scaffolds, as evidenced by an upregulation of β-actin and a down regulation of α-smooth muscle actin and collagen type I mRNA. Taken together, these data indicate that biocompatible nanomaterials have the capacity to regulate fibroblast-mediated matrix remodeling. Targeted delivery of nanomaterials may represent a novel mechanism for managing pathological cardiac remodeling.
9:00 PM - FF3.34
Pure-Silica Zeolite ITQ-29 (LTA) Low-k Films via Vapor Phase Transport Method.
Heather Hunt 1 , Christopher Lew 2 , Yushan Yan 2 , Mark Davis 1
1 Chemical Engineering, California Institute of Technology, Pasadena, California, United States, 2 Chemical and Environmental Engineering, University of California, Riverside, Riverside, California, United States
Show Abstract9:00 PM - FF3.5
Bioinstructive Nanostructured Interfaces for the Control of Cell Differentiation.
Tobias Wolfram 1 2 , Christian Gojak 1 2 , Ferdinand Belz 1 2 , Daniel Aydin 1 2 , Joachim Spatz 1 2
1 New Materials and Biosystems, Max-Planck-Institute for Metals Research, Stuttgart Germany, 2 Biophysical Chemistry, University of Heidelberg, Heidelberg Germany
Show AbstractMicro- and nanostructured bioinstructive materials are now widely used to investigate complex cellular behavior like cell adhesion and to mimic cell-cell contacts and cell-substrate interactions. So far, most of the studies using these new materials are restricted to biomolecules which show cell adhesion functions, like fibronectin, laminin, cadherins or peptide cell binding motifs from those proteins. Polypeptides such as growth factors or bioinstructive transmembrane proteins like Delta and its receptor Notch regulate and modulate key cell function with respect to cell differentiation and tissue development but most of these molecules show little or no cell adhesion activity.We developed a method for the immobilization of single recombinant proteins on nanostructured gold nanoparticle substrates. The amount of molecules and the manner in which the protein is presented to cells can be controlled. In addition, we used a new approach to prepare multifunctional nanostructured substrate based on poly-l-lysine-grafted polyethylene glycol to mimic a complex cellular microenvironment featuring adhesive and instructive cues from the substrates covered with gold nanoparticles. We used Immunofluorescence Microscopy, Scanning Electron Microscopy and Quartz Crystal Microbalance with Dissipation monitoring to evaluate and control the preparation of nanostructured jagged-1 substrates with different cell adhesion molecules or cell adhesive cues (like laminin, fibronectin, N-Cadherin, and gelatine) in between the gold nanoparticles. With these bioinstructive substrates we addressed the question whether molecular nanopatterns of jagged-1 proteins can influence the differentiation of C2C12 mouse myoblast cells into myotubes. Myotube differentiation was evaluated with different fluorescence markers (myosin heavy chain, actin, and nuclei) and cell morphological aspects (size of myotubes and number of myotubes) on 30, 60 and 140 nm spaced jagged-1 substrates. The formation of myotubes was reduced on 30 and 60 nm spaced substrates, 140 nm patterns did not show different results from the jagged-1 free controls. Interestingly, cell proliferation measured by BrdU-staining showed the reverse case with higher activity on the lower spaced substrates. The molecule used as the adhesive cues in between the nanoparticles did not show a great influence on differentiation events but were important for the ability of the cells to adhere to the biofunctionalized material. Initial experiments show that jagged-1 functionalized materials do not have a similar influence on the differentiation of C2C12 cells into osteoblasts then on myotube formation. Our approach provides a possibility for micro- and nanostructured biomolecules on synthetic biomaterials to mimic closely cellular microenvironments for the control of cell differentiation aspects.
9:00 PM - FF3.6
Electrical Conductivity of Hydrogels with Gold Nanoparticles.
James Alaimo 1 , Andrew Marshall 1 , Celeste Peay 2 , Delphine Dean 1
1 , Clemson University, Clemson, South Carolina, United States, 2 , Mauldin High School, Greenville, South Carolina, United States
Show AbstractElectrically conductive biocompatible gels are useful as coatings on electrode implants interfaces as well as for various engineered tissue constructs. Currently, many groups are investigating the development of new electrically conductive polymers for these applications. Unfortunately, one limitation of these new polymers is that they are not yet approved by regulatory agencies. When an electrode is implanted, a collagenous fibrous layer tends to form around it due to immune responses and poor biocompatibility. This collagen layer allows for good cell attachment but creates large resistance for electrical signaling to the electrode surface. In this study, we propose to use gold nanoparticles to vary the conductance of collagen gels. Gold nanoparticles are readily available and conductive. At low concentration inside a collagen gel, they do not affect the interaction between cells and the matrix. The conductance of the gels was measured in a custom DC conductance measurement setup. In this setup, gels are made in a small (15mm x 20mm x 0.3mm) glass chamber with two parallel silver electrode wires. 1mg/ml collagen type I gels were cast between the electrodes. In half the samples, 20nm gold nanoparticles were dispersed in the suspension prior to gelation (while maintaining the gel concentration at 1mg/ml). The average bulk conductivity of the gels with less than 0.01% gold nanoparticle content was measured to be nearly 2x higher than that of the control gels (6.3Sm). Similar changes in conductance were also seen with alginate hydrogels. Since very small amounts of nanoparticles have large effect on the conductance of gels, this technique may be used to modify the conductance of other gel types without greatly affecting their cell compatibility.
9:00 PM - FF3.7
Immobilization of Thyroid Nuclear Receptors in Ultrathin Nanostructured Films for Sensing.
Luana Bendo 1 , Ana Figueira 1 , Igor Polikarpov 1 , Valtencir Zucolotto 1
1 , University of São Paulo, São Carlos Brazil
Show AbstractNuclear receptors represent a class of transcriptional regulators, which main function is to regulate specific biological processes including homeostasis and metabolism. They act as transcription signaling that respond directly through physical association with a large variety of hormonal and other regulatory signals. The thyroid hormone receptors (TH), in particular, are encoded by two genes, TRα and TRβ, which belong to a superfamily of transcriptional regulatory molecules. In this study, the isoform TRβ1 was immobilized in multilayered ultrathin films onto the surface of microelectrodes for biosensing. The microelectrodes containing the TRβ1 were applied to the detection of specific ligand agonists, including the hormone T3 (triiodothyronine) and GC-1 (3, 5-dimethyl-4-(4’-hidroxy-3’-isopropylbenzyl phenoxy) acetic acid). The detection of T3 and/or GC-1 was carried out via impedance spectroscopy, in which the capacitance of the electrode/TRβ1 system was monitored in the presence of different concentrations of the analyte (T3 or GC-1). To improve the efficiency of the detection technique, three electrodes were employed, viz., bare electrode; an electrode containing an organic thin film comprised by layers of poly(allylamine hydrochloride) (PAH) and poly (sodium 4-styrenesulfonate) (PSS), and the electrode containing the immobilized TRβ1. After the electrical experiments the capacitance values for the three electrodes used were statistically correlated, and the sensor was capable of detect and distinguish between the hormones T3 and GC-1 at concentration down to 10-4 mg/ml.
9:00 PM - FF3.8
Characterization of Potential Health Effects of Fluorescent Quantum Dots.
Yu Jin Lee 1 , Sung Yang 1
1 Chemistry, Kyung Hee Univ., Yongin Korea (the Republic of)
Show AbstractFluorescent nanoparticles such as CdS, CdSe have attracted extensive attentions due to their potential applications in nano-electronics, nano-photonics, chemical sensing, and biological imaging. In particular, CdS and CdSe have been of considerable interest due to their high fluorescence quantum yield, which makes them ideal candidates for biological imaging and labeling. However, there is a possible health and environmental effects since Cd2+ is one of the toxic materials. So, it is essential to evaluate the possible health effects of fluorescent quantum dots including the hazardous properties and the dose-response relationships. We have characterized the physico-chemical properties including size, shape, surface area, surface chemistry of CdS and CdSe and their relationship with toxicity in nerve cell.
9:00 PM - FF3.9
Catalytic Activity of Nanoparticles–Carbon Nanotube Hybrid Nanostructures.
Wonil Park 1 , Jeunghee Park 1 , Yoon Myung 1 , Dongmyung Jang 1 , Jinwoo Cho 1 , Hansung Kim 1 , Byoungkoun Min 2
1 Material Chemistry, Korea University, Jochiwon Korea (the Republic of), 2 Energy & Environment Research Division, Korea Institute of Science and Technology, Seoul Korea (the Republic of)
Show AbstractSince their discovery in 1991, carbon nanotubes (CNTs) have attracted a tremendous amount of attention due to their extraordinary physical, chemical, and mechanical properties. The large surface area of the CNTs offers abundance reactive sites to generate Faradic currents, and the reactions on CNT-modified biosensor (typically glucose sensors) electrodes belong to the surface-controlled process and have shown direct electron transfer property. We fabricated non-enzymatic amperometric glucose biosensors using nanoparticles (e.g., Pt, Ru, Pd, Cu2S, avg. size = 8 nm)-CNT hybrid nanostructures, synthesized directly by the solvothermal method. In particular, the Cu2S nanoparticles decomposed catalytically the glucose into H2O2, and enhance greatly the performance of glucose sensors which is comparable to the enzymatic sensors. Furthermore, photocatalytic degradation of 1,4-dioxane has been also activated by more various nanoparticles including ZnS, CdS, and CdSe, showing the highest efficiency of beta-Cu2S nanoparticles under visible irradiation. The major intermediate is found to be ethylene glycol diformate and H2O2, suggesting the formation of Fenton reagent. Hybridization of CNTs enhances the degradation yield via the improved adsorption ability.
Symposium Organizers
Larry Nagahara National Cancer Institute
Thomas Thundat Oak Ridge National Laboratory
Sangeeta Bhatia Massachusetts Institute of Technology
Anja Boisen Technical University of Denmark
Kazunori Kataoka The University of Tokyo
FF4: In-vitro Diagnostics using Nanodevices
Session Chairs
Larry Nagahara
Thomas Thundat
Tuesday AM, December 02, 2008
Room 304 (Hynes)
9:00 AM - FF4.1
Using a Synthetic Nanopore like a Molecular Sieve to Differentiate Methylated from Unmethylated DNA.
Winston Timp 1 , Utkur Mirsaidov 2 , Changbae Hyun 2 , Xueqing Zou 2 , Klaus Schulten 2 , Andrew Feinberg 1 , Greg Timp 2
1 Medicine, Johns Hopkins University, Baltimore, Maryland, United States, 2 Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
Show AbstractMethylation of cytosine residues in DNA produces 5-methylcytosine, changing the protein binding affinity of the sequence and hence altering the organization and expression of the surrounding DNA. The pattern of methylation often silences genes, which physiologically orchestrates processes like differentiation, and pathologically leads to cancer. Methods of methylation detection are limited. Restriction enzymes recognize only specific methylation sites. DNA immunoprecipitation(MeDIP) shows poor sensitivity. And bisulfite DNA sequencing relies on the chemical conversion of cytosine to uracil by sodium bisulfite, offers single-base resolution, but the cost is high—$10,000 per megabase of sequence data, so it is limited to only small lengths of DNA We are motivated to explore the nanoelectromechanical properties of methylated DNA, to discover if there was a better method of differentiating it from unmethylated DNA. Here, we report measurements of the permeation of methylated DNA through a synthetic nanopore, using an electric field to force single molecules to translocate one-at-a-time. For pores <2.0 nm in diameter—smaller than the DNA helix—we found an electric field threshold for permeation of methylated DNA that depends on the methylation level and pattern.We used a single synthetic nanopore, created in a thin Si3N4 membrane through electron beam stimulated decomposition. After characterizing the pores using ionic conductance measurements, we tested the electric field driven permeability of DNA through the pore. We tested three strands of 88 bp long double stranded DNA: one unmethylated; one hemi-methylated at 5 sites of one strand; and another fully-methylated at 5 sites in each strand. We injected a concentration of 109 molecules/μL into the cathode of the bi-cell used for the transport measurements. A voltage was then applied across the membrane, and the current through the pore was monitored for 3 hours. Using real-time, quantitative PCR, we measured the number of DNA copies which translocated across the membrane through the nanopore at a given voltage.We found that the unmethylated, hemi-methylated and fully methylated DNA strands each had a different threshold voltage for translocation. For fully- and hemi-methylated DNA the threshold voltages are consistently below that observed for unmethylated DNA and easily resolved. For example, the threshold for umethylated DNA in a 1.8 nm diameter pore is about 3.61V while hemi- and fully-methylated DNA show a threshold of 3.11 V and 2.73 V respectively. The change in threshold is also consistent with features observed in MD simulations. The large difference in threshold voltage for permeation can be potentially used to read out the methylated sites of DNA and might offer an alternative approach to current techniques. It also has interesting implications for the effect of methylation on the mechanical characteristics of the double helix.
9:15 AM - FF4.2
Fabrication of Gating Nano-Pore Device.
Tomoji Kawai 1 , Masateru Taniguchi 1 , Makusu Tsutsui 1 , Takeshi Yanagida 1
1 ISIR-Sanken, Osaka University, Osaka Japan
Show AbstractResearch on production of solid-state nanopores on silicon substrates, with the aim of developing a biosensor or a high-speed DNA sequencer, is proceeding at a rapid pace. Solid-state nanopores have excellent stability and durability, similar to bio-nanopores, and can be used to obtain the number of molecules passing through the nanopore as well as to measure their dynamics[1-3]. However, since the operation principle of this device is based on that of the patch clamp technique, it is difficult for the device to provide detailed information and it cannot identify the molecule type. In particular, since the present solid-state nanopore structure has no molecular recognition ability, realization of a DNA sequencer is very difficult. Here we report the fabrication of a gating solid-state nanopore structure comprising nanoelectrodes combined with solid-state nanopores. This device structure has one pair of electrodes arranged in parallel with the nanopores and another pair arranged orthogonally. Usually, patch clamp measurement is performed using the electrodes arranged in parallel. Furthermore, molecules passing through the nanopore can be identified by passing an electric current through the orthogonally arranged nanoelectrodes. A gating solid-state nanopore structure was fabricated using the following processes. First, nanoelectrodes were produced by electron-beam (EB) lithography and the liftoff process on the silicon substrate. Next, a nanopore was produced by EB lithography and dry etching using a chromium mask. Finally, the mask window was produced on the back side of the silicon substrate by EB lithography, and freestanding Si3N4 was produced by wet etching of silicon. We succeeded in producing the gating solid-state nanopore with a minimum diameter of 40 nm by the present method. Further, in order to investigate whether a single molecule can be identified via electrical measurement, a nanostructure combining a nano-mechanically controllable break junction[4] and a micro-fluid (width: 2 mm) was produced. A gold nanoparticle with a diameter (in a citric acid solution) of 2 nm was passed through the nanopass, and the time dependence of electric current between nanoelectrodes was measured; the distance between the nanoelectrodes was 2 nm. An electric signal originating from the gold nanoparticle was observed.[1] C. Dekker, Nat. Nanotech. 2, 209 (2007).[2] J. Li, et al., Nat. Mater.,2, 611 (2003).[3] U. F. Keyser, et al., Nat. Phys. 2, 473 (2006).[4] T. Kawai, et al., Nano Lett. 8, 345 (2008).
9:30 AM - FF4.3
Development of a Nanopore-based Electrical Device for Controlling the Translocation of DNA with Single Base Resolution.
Hongbo Peng 1 , Stephen Rossnagel 1 , Stanislav Polonsky 1 , Gustavo Stolovitzky 1
1 , IBM T. J. Watson research center, Yorktown Heights, New York, United States
Show AbstractHighly negatively charged DNA molecules can be electrically driven through a pore of a few nanometers in diameter (nanopore). During the last 10 years, nanopores have been proposed or demonstrated as sensors for rapid analysis of biomolecules (DNA, RNA, protein, etc.) or interactions between these biomolecules. Application of nanopores to low-cost DNA sequencing is particularly attractive as there is great need to reduce the cost for sequencing a whole human genome to $1000. A key issue in the field of nanopore DNA sequencing is to control the DNA translocation. Here we will report the development of what we call a DNA transistor: a nanopore-based electrical device for controlling the translocation of DNA with single base resolution. The key part of this device is a free standing membrane, made of metal/dielectric/metal/dielectric/metal, with the thickness of each layer about 2 or 3 nm. A nanometer size (about 3 nm) pore is made through the membrane. Voltage biases are applied on the metal layers to modulate electrical field inside the nanopore. Our ongoing experiments test if the modulated electrical field can trap or translocate DNA in a controllable way. This device can also be used to replace the costly electrophoresis step in Sanger’s DNA sequencing method.
9:45 AM - FF4.4
Solid State Nanopores with Integrated Carbon Nanotubes for Single Molecule Electronic Detection and DNA Sequencing.
Slaven Garaj 1 , Dimitar Vlassarev 1 , Daniel Branton 2 , Jene Golovchenko 1 3
1 Department of Physics, Harvard University, Cambridge, Massachusetts, United States, 2 Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States, 3 School of Engineering and Applied Science, Harvard University, Cambridge, Massachusetts, United States
Show Abstract10:00 AM - **FF4.5
Detection of Small Molecules using Porous Silicon Optical Waveguides.
Sharon Weiss 1
1 EECS, Vanderbilt University, Nashville, Tennessee, United States
Show AbstractThe detection of low molecular weight molecules is a major challenge for many types of biosensors. Recently, porous silicon waveguide sensors have been demonstrated for the detection of molecules as small as single DNA bases. In contrast to traditional optical sensors that are based on evanescent wave detection, porous silicon waveguide sensors subject target molecules to large propagating fields of guided modes. The electric field is locally confined in the active sensing region, in the waveguide core, where target molecules are captured. The large surface area available for molecular immobilization and binding in the porous silicon waveguides further facilitates small molecule detection. This talk will discuss in detail the fabrication, characterization, and principle of operation of porous silicon waveguide biosensors. Waveguide mode excitation is achieved by means of a prism or a photoresist grating that is directly fabricated on the waveguide core by electron beam lithography. A comparison of the electric field distribution of porous silicon waveguides and several evanescent-wave based sensors will be shown to highlight the light-matter interaction in these systems. A simple alternative for the traditional surface plasmon resonance sensor will also be presented, where the gold layer is replaced by a porous silicon waveguide. Finally, the critical relationship between pore size, biomolecule size, and detection sensitivity will be addressed.
10:30 AM - FF4.6
Diagnosing Lung Cancer by Random Network of Single-Walled Carbon Nanotubes Coated with Non-Polymeric Organic Materials.
Gang Peng 1 , Elena Trock 1 , Hossam Haick 1
1 The Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa Israel
Show AbstractRecent statistics have estimated that there were nearly 2.9 million new cases diagnosed in 2004 and over 1.7 million deaths from cancer in US, with lung cancer as the commonest form of cancer diagnosed and of cancer death. In this study, we have developed an array of sensors to detect lung cancer and to differentiate between the Volatile Organic Compounds (VOCs) found in the breath of patients with lung cancer, relative to healthy controls. A technology, in which a (semi-) conductive random network of single-walled carbon nanotubes (SWCNTs) and insulating non-polymeric organic materials provide arrays of vapor detectors form the basis for our approach. The study was designed in two main phases. In the first phase, alveolar breath was collected from individuals with lung cancer and from healthy subjects and analyzed with GC-MS, to reveal the characteristics of VOCs in the collected breath samples. In the second phase, the major VOCs found in the healthy and diseased states were simulated and exposed to the developed array of sensors that were conjugated with machine learning algorithms. Our results indicate that the array of the developed sensors has a high potential for diagnosis of lung cancer via breath samples. The sensors array showed excellent discrimination between the VOCs found in the breath of patients with lung cancer, relative to healthy controls, especially if the sensors array is preceded with either water extractor and/or pre-concentrator of VOCs. The obtained results with simulated biomarkers were compared with responses from the same array of sensors that were exposed to real alveolar breath. A reliable correlation was found between the two classes of responses. The developed devices are expected to be relatively inexpensive, portable, and amenable to widespread screening. Given the impact of rising incidence of cancer on health budgets worldwide, the proposed technology will be a significant saving for both private and public health expenditures. The potential for using the proposed technology towards other diseases and conditions make it of further great interest.
10:45 AM - FF4.7
A Micro-radiotherapy System based on Carbon Nanotube Field Emission Technology for Cancer Research.
Sigen Wang 1 2 , Xiomara Calderon 2 , Rui Peng 2 , Shabana Sultana 2 , Eric Schreiber 1 , Otto Zhou 2 , Sha Chang 1
1 Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina, United States, 2 Department of Physics and Astronomy, University of North Carolina, Chapel Hill, North Carolina, United States
Show AbstractIn this presentation, we report the design, fabrication, assembly and test of a novel multi-pixel array x-ray micro-radiotherapy (micro-RT) system which is based on carbon nanotube (CNT) field emission technology for fast conformal and intensity-modulated radiotherapy (IMRT) irradiation for small animals. The proposed micro-RT system is capable of electronically form different shape radiation fields and different intensity modulation patters by “turning on” a sub-set of the x-ray pixel beams. The micro-RT system comprises a CNT pixel cathode array for individual pixel beam generation and control, a transimission type anode for x-ray production, and a pixel beam collimation array to converts the x-rays to pixel beam x-ray beams. Each x-ray pixel beam is 2 mm x 2 mm at the irradiation object and the beam energy should be 100 kV or higher. Monte Carlo based dosimetric simulation and electro-optical simulations are performed to guide the system design. The micro-RT offers a maximum radiation field size of 10 mm x 20 mm at the irradiation object. The preliminary test results show that one cathode pixel of the micro-RT can produce 3.7 mA peak emission current. Monte Carlo simulations indicated that it is expected that 3.7 mA emission current can generate a dose rate of >1.2 Gy/min at the center of mouse under the micro-RT irradiation.
11:30 AM - **FF4.8
Magneto-nano DNA and Protein Chips for Multiplex Molecular Diagnostics.
Shan Wang 1
1 Materials Science and Engineering, Stanford University, Stanford, California, United States
Show Abstract12:00 PM - FF4.9
Magnetic Bead Detection using LC resonator type Giant Magneto Impedance Sensors.
Dohun Kim 1 , Won Young Jeung 1
1 Functional Materials Research Center, Korea Institute of Science and Technology, Seoul Korea (the Republic of)
Show Abstract12:15 PM - FF4.10
Chemically-Functionalized Biotransistor for Noninvasive and High-throughput Monitoring of Apoptosis.
Takashi Chin 1 , Taiichiro Murakami 2 , Akira Matsumoto 1 3 , Toshiya Sakata 2 3 4 , Madoka Takai 2 3 , Kazuhiko Ishihara 1 2 3 , Yuji Miyahara 2 3 4
1 Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo Japan, 2 Department of Materials Engineering, School of Engineering, The University of Tokyo, Tokyo Japan, 3 Center for NanoBio Integration, The University of Tokyo, Tokyo Japan, 4 Biomaterials Center, National Insititute for Materials Science , Tsukuba Japan
Show AbstractSince the concept of micro total analysis system (µ-TAS) has immerged in the fields of medical care research and drug discovery, the biosensor technology has attracted great deal of research interests. Our group has thus far successfully demonstrated a series of electrical detections of bio-molecular recognition events using biologically coupled field effect transistors (biotransistors), techniques relevant to genetic and cell-functional analyses. The principle of biotransistor is based on potentiometric detection of charge density change, which is induced at a gate insulator/solution interface by specific biomolecular recognition. In particular, the biotransistor allows one to noninvasively monitor the cell function on the basis of intrinsic molecular charge detections at nano-scale interface between cell membrane and the gate insulator. A number of studies have suggested strong relationships between apoptosis (programmed cell death) and various diseases including those related to Alzheimer’s. Elucidation of apoptosis is increasingly important due to its direct feedback to medical care and pharmaceutical lead discovery. In this study, we have designed functional membrane at the biotransistor interface with an attempt to conduct noninvasive and high-throughput detection of apoptosis. First, Hela cells were seeded with concentration of 3~5x105 cells/ml on the Ta2O5/SiO2 gate surface of a biotransistor. Human TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) was introduced to the cell covered gate surface after 12 hours incubation for induction of apoptosis. Changes in electrical characteristics of the biotransistor were monitored during 24 hours incubation. Upon addition of TRAIL onto the cell covered gate surface, it was observed that the surface potential progressively increases, presumably due to the capture of K+ ions released from the cells while undergoing apoptosis. Then, finally, the surface potential started decreasing at the rate of 1 mV/h after 3 hours incubation, corresponding to the commencement of the diffusion of K+ ions. Furthermore, to clarify the cause of the observed increase in surface potential, the gate of biotransistor was modified with crown ether moieties that are sensitive to K+ ion. As a result, it was revealed that the surface potential increases at the rate of 1 mV/h over 5 hours after introduction of TRAIL, which thus was correlated to K+ ion released from ion channels at cell membrane at early stage of apoptosis. Thus we conclude that such biotransistor based detection platform herein demonstrated in combination with the design of functional bio-interface could provide an option for noninvasive, real-time and high-throughput monitoring of apoptosis directly applicable to medical care and drug discovery.
12:30 PM - FF4.11
Non-invasive and Quantitative Monitoring of Cell Membrane Carbohydrates using Phenylboronic Acid Gate Modified Field Effect Transistor.
Akira Matsumoto 1 2 , Naoko Sato 1 3 , Toshiya Sakata 1 3 , Chiho Kataoka 4 , Kazunori Kataoka 1 2 3 , Yuji Miyahara 1 4
1 Center for NanoBio Integration, The University of Tokyo, Tokyo Japan, 2 Dept. of Bioengineering, The University of Tokyo, Tokyo Japan, 3 Dept. of Materials Science, The University of Tokyo, Tokyo Japan, 4 Biomaterials Center , National Institute for Materials Science, Tokyo Japan
Show AbstractThe ability to non-invasively quantify biological substances provides advanced options for analytical biochemistry and clinical diagnostics, where, ideally, the detection scheme should completes without the need for target-labeling procedures that are costly and complex. Field effect transistor (FET) based technique represents a unique detection platform, in which intrinsic molecular charges immobilized on the gate surface, upon electrostatic interaction with the thin-insulator-segregated silicon electrons, can directly be transduced into electrical signals. Based on the principle, a number of label-free biosensing systems have been so far demonstrated including immunoensors, DNA sequencing and even detection of single-nucleotide polymorphism (SNP). This work reports on an FET based non-invasive and label-free detection of carbohydrate molecules that are present on cell membrane. A totally synthetic and chemically stable sugar-binding moiety, phenylboronic acid (PBA), was introduced in the form of self-assembled monolayer (SAM) onto an extended Au gate surface. It was demonstrated that, under physiological pH and ionic strength conditions, the prepared PBA-modified FET could specifically detect sialic acid moiety (Neu5Ac) among other naturally occurring mono-saccharides such as glucose, galactose and mannose, with the sensitivity on the order of 100 pM. Further, it was demonstrated that the PBA modified FET was capable of quantify the number of erythrocyte in the milieu in a completely non-invasive manner by monitoring the change in the threshold gate voltage (VT), due to interactions between PBA and carbohydrate sialic acid moieties present on the erythrocyte membrane surfaces. It was also possible to distinguish native and sialidase treated cells by comparatively studying the “cell number” vs “VT shift” profiles, indicating the ability to quantify the density of sialic acid on a single cell. PBA moiety is known to interact with the natural biological membranes of a variety of cells, viruses, bacteria, and fungi through the membrene-constituting carbohydrate moieties. With potential ability to perceive those biological membrane interactions and to do so in non-invasive, label-free and real-time manner, the PBA-modified transistor described here may also be applicable to non-invasive types of cytology.
12:45 PM - FF4.12
Multiplexed Nanowire Nanoelectronic – Heart Interfaces.
Tzahi Cohen-Karni 2 , Brian Timko 1 , Guihua Yu 1 , Quan Qing 1 , Bozhi Tian 1 , Charles Lieber 1 2
2 School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States, 1 Chemistry and Chemial Biology, Harvard University, Cambridge, Massachusetts, United States
Show AbstractThe interface between nanoscale electronic devices and biological systems enables interactions at length-scales natural to biology, and thus should maximize communication between these two diverse yet complementary systems. In this work, we report electrical properties of nanowire field-effect transistor (NWFET) arrays interfaced with spontaneously-beating embryonic chicken hearts. Simultaneous electrical recordings from glass microelectrode and NWFET devices demonstrate that NWFET signals are synchronized with the beating heart with nanowire signal amplitude directly related to the device transconductance. Multiplexed measurements made from NWFET arrays further show that signal propagation across the myocardium can be mapped, with a potential resolution significantly better than microelectrode techniques. In addition, we exploit the unique capability of bottom-up approach to fabricate NWFET arrays on flexible and transparent plastic substrates, and demonstrate that these novel device arrays enable multiplexed signal recording in a number of conformations as well as registration of devices to the heart surface. The assembly of flexible arrays of reproducible NWFET structures opens up opportunities for fundamental studies of cardiac biophysics, real-time drug assays, and potential for novel implants.
FF5: Nanodevices for Screening and Analysis
Session Chairs
Tuesday PM, December 02, 2008
Room 304 (Hynes)
2:30 PM - **FF5.1
Technologies for Probing the Paradoxical Relationship of the Immune System and Cancer.
Gabriel Kwong 1 , Rong Fan 1 , Caius Radu 2 , Antoni Ribas 3 , Owen Witte 4 , James Heath 1
1 Chemistry, California Institute of Technology, Pasadena, California, United States, 2 Molecular & Medical Pharmacology, University of California Los Angles, Los Angeles, California, United States, 3 Hematology & Oncology, University of California Los Angles, Los Angeles, California, United States, 4 HHMI/Microbio, Immunol & Mol Genet/ISCBM, University of California Los Angles, Los Angeles, California, United States
Show Abstract3:00 PM - FF5.2
Oligonucleotides Immobilization and Messenger Ribonucleic Acid (mRNA) Isolation for a Real-Time Genetic Analysis Device.
Chantelle Hughes 1 , Malathi Banda 2 , Joseph Smolinski 1 , Robert Thomas 2 , James Tucker 2 , Gregory Auner 1 3
1 Electrical and Computer Engineering, Wayne State University, Detroit, Michigan, United States, 2 Biological Sciences, Wayne State University, Detroit, Michigan, United States, 3 Biomedical Engineering, Wayne State University, Detroit, Michigan, United States
Show AbstractWorking towards the goal of developing a portable, real-time polymerase chain reaction (PCR)-based device, a first generation prototype device has been developed. The prototype has been utilized to examine levels of cellular damage in human lymphocytes that were exposed to low-doses of ionizing radiation. In terms of the effects of radiation exposure on human lymphocytes, 20+ dose-dependent genes (evident by up- or down-regulation) and 6 dose-independent (house-keeping) genes (no changes in regulation) have been identified. The bench-top prototype is capable of performing genetic analysis with only a drop of blood (approximately 50 micro-liters) and consists of a few main components: 1) cell lyses region, 2) immobilization region for mRNA isolation, and 3) a real-time PCR portion, for gene amplification and analysis. Key to the device development was the integration of a novel, near-molecular binding platform for the detection, immobilization, and isolation of mRNA from lysed whole blood components. Within the Pyrex-based prototype, it was crucial that the binding platform be selective and specific for targeting mRNA during the immobilization and isolation processes. In addition, it had to be reversible, so that mRNA could be released from the surface during the reverse transcription process for the cDNA (complementary deoxyribonucleic acid) formation. It was also essential that the binding platform be durable and stable enough to endure the various rinsing cycles (necessary for cellular debris removal) and temperature fluctuations, since extended heating and cooling cycles were critical for the release of mRNA from the surface and reverse transcription. Hence, the novel use of 10-(carbomethoxy)decyl-dimethylchlorosilane (CMDDCS) to hydroxylated Pyrex-surfaces for the covalent immobilization of 5’-end amine-modified oligonucleotides [polyT25 (twenty-five thymine bases)] was examined. To our knowledge CMDDCS has not been presented for the immobilization of nucleic acids to surfaces. For CMDDCS, both liquid and chemical vapor deposition (CVD) techniques were studied. Methods used to convert the terminal ester-group to a carboxylic acid will be described. Heterobifunctional crosslinkers were utilized to promote the covalent binding of amines to the CMDDCS-modified carboxylic acid surface. Analyses for the detailed binding processes on Pyrex surfaces and the prototype device will be presented. Atomic force microscopy (AFM) and x-ray photoelectron spectroscopy (XPS) were utilized to characterize the substrate surfaces pre- and post-CMDDCS deposition. Fluorescent microscopy was used to characterize oligonucleotide and mRNA substrate coated surfaces. PCR and real-time PCR (from an established system) were utilized to characterize cDNA (post-transcription) released from the prototype; real-time PCR and gel electrophoresis data will be presented.
3:15 PM - FF5.3
Nanoparticle-based, Miniaturized Magnetic Resonance System for Clinical Applications.
Hakho Lee 1 , Tae-Jong Yoon 1 , Ralph Weissleder 1
1 Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States
Show AbstractWe have developed a chip-based, diagnostic magnetic resonance (DMR) system that can perform rapid, quantitative and multichanneled detection of biological targets. The DMR system utilizes magnetic nanoparticles to amplify molecular interactions; when a few magnetic nanoparticles bind their intended molecular targets, they form nanoscale clusters that efficiently dephase magnetic moments (spins) of surrounding water protons to significantly shorten spin-spin relaxation time (T2) of bulk water. Because the DMR relies on nuclear magnetic resonance (NMR) for signal detection, the interference by media, that are transparent to magnetic fields, becomes negligible, making it possible to perform measurements in native biological samples (for example, blood, sputum and urine) with few or no preparation steps. As proof of concept, we have implemented a DMR prototype that consists of a miniaturized microcoil chip, microfluidic networks and a permanent magnet. The microcoils are used as a transceiver for NMR detection. Multiple coils are arranged in an array format to enable multiplexed, parallel detection. The microfluidic networks provide on-chip mixing between magnetic nanoparticles and biological samples and confine the mixture to microcoils for maximal NMR signal generation with small sample volumes (5–10 μl). By employing a compact permanent magnet and a single-board spectrometer, the whole DMR system is then packaged for point-of-care operation. Using the first prototype, here we demonstrate high sensitivity and clinical utility of the DMR system; we were able to detect a few bacteria and a single mammalian cell in 10 μl sample volumes, selectively profile cancer cells according to their cell-surface proteins, and screen different serum conditions via multiplexed identification of biomarkers. Combining the advantages of nanotechnology, microelectronics and microfluidics, we anticipate the DMR system can be a powerful tool as a highly sensitive, easy-to-use and portable diagnostic platform.
3:30 PM - FF5.4
Integration of Surface-directed Microfluidic System with Biological Sensors Based on Organic Electrochemical Transistors.
Sang Yang 1 , Yuri Sylvester 1 , Daniel Macaya 1 , John DeFranco 1 , George Malliaras 1
1 Materials Sciences and Engineering, Cornell University, Ithaca, New York, United States
Show AbstractCapability for multianalyte biological sensing of organic electrochemical transistor (OECT) based on solution processible poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) was demonstrated and the effective integration of those sensor arrays with surface-directed microfluidic system for the multianalyte sensing microfluidic device was achieved by the optimization of fabrication process. A surface-directed spontaneous flow of aqueous analyte solutions was guided to array of PEDOT:PSS OECT sensing devices by means of capillary force generated by hydrophilic channel surrounded by hydrophobic (tridecafluoro-1,1,2,2-tetrahydrooctyl)trichlorosilane monolayer on glass substrate. When different enzyme solutions were added on each of OECT sensor, the relatively dramatic change of conductivity in PEDOT:PSS OECT sensors where electrochemical process of specific analyte/enzyme reaction occurs makes it possible to identify what kinds of analytes were contained in the unknown or multi-analyte solution. Therefore, the integrated devices showed the potential of single-use multianalyte biosensing devices, which can detect the specific analytes from a single sample of multianalyte solution with a few microliters. The application of the spontaneous flow of analyte solutions without external tools to apply the pressure and the possibility for the fabrication of PEDOT:PSS OECTs on plastic substrates can provide new prospects of the realization of the cheap and single-use (disposable) ‘plastic bioelectronic’ devices for multianalyte sensing.
3:45 PM - FF5.5
Phospholipid Polymer-modified Field Effect Transistor for Sensitive Detection of Biomolecular Recognition.
Koji Futamura 1 , Akira Matsumoto 2 3 , Toshiya Sakata 1 3 , Madoka Takai 1 3 , Kazuhiko Ishihara 1 2 3 , Yuji Miyahara 1 3 4
1 Department of Materials Engineering, The University of Tokyo, Tokyo Japan, 2 Department of BioEngineering, The University of Tokyo, Tokyo Japan, 3 Center for NanoBio Integration, The University of Tokyo, Tokyo Japan, 4 Biomaterials Center, National Institute for Materials Science, Tsukuba Japan
Show AbstractRecently, many types of biosensors have been utilized in molecular biology, pharmacogenomics, and clinical research. In particular, DNA chips that are usually combined with fluorescence-labeling techniques represent important detection platforms for gene expression analyses and genotyping. Above all, techniques to detect single nucleotide polymorphism are of increasing interest due to their expected benefits in realizing “tailored medicine” developments. We have previously reported some methods for potentiometric detections of DNA recognition events using a field effect transistor (FET), a miniaturized and inexpensive technique since it requires neither complex labeling procedures nor large optical instruments. In this study, we aim to fabricate the functional polymer-modified FET for DNA detection with a high signal to noise ratio by reducing non-specific biomolecule adsorption on the gate sensing area. The gate surface of the FET was modified with a layer of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer. The chemical structure of MPC mimics that of cell membrane and it shows an excellent biocompatibility. Remarkable inhibitions of non-specific biomolecule adsorption onto the MPC-modified surfaces have already been known. Therefore, ultimately, the MPC-modified FET may be even applicable to a whole blood analysis when it is combined with Ampdirect® which enables us to have direct polymerase chain reaction (PCR) from whole blood without DNA isolation. Poly(MPC-co-3-methacryloxypropyltrimethoxysilane (MPTMSi)) (PMSi) was covalently introduced onto the gate surface by promoting a silane coupling reaction. The surface was then amino-silanized. DNA probes were immobilized by using glutaraldehyde as a bifunctional cross-linker. For hybridization with target DNA, the PMSi-modified FET with DNA probes was kept in the hybridization solution. The shifts of threshold voltage (VT) in the VG-ID characteristics were measured after immobilization of probes and then hybridization with targets. In both cases the VT shifted in the positive direction due to intrinsic negative charges of deoxynucleotides. The magnitudes of the VT shift at 1500 μA after the probe immobilization and the hybridization were 149 mV and 47 mV, respectively. These shifts were about 4-times bigger than those obtained by the previous method. This is because the immobilization density of DNA probes increased in the MPTMSi layer as well as at the gate surface. Moreover, after contacting the PMSi-modified FET to the DNA hybridization solution and protein solution, it was confirmed that PMSi-modification effectively reduced the non-specific DNA and protein adsorptions compared to the bare-FET. Thus, the PMSi-modified FET with PCR from whole blood could provide an option for designing a whole blood analysis. The platform based on the FET combined with the functional polymer is suitable for a highly sensitive detection system for genetic analysis.
4:30 PM - **FF5.6
Micro- and Nanoscale Devices for Biomolecular Detection and Single Cell Analysis.
Scott Manalis 1
1 , MIT, Cambridge, Massachusetts, United States
Show AbstractThis talk will present an overview of applications where the unique physical properties associated with micro- and nanoscale dimensions have been exploited for developing precision measurement methods. Applications are primarily based on an ultrasensitive mass sensor known as the suspended microchannel resonator (SMR) which places the fluid inside of the resonant cantilever structure, and Teflon valves and pumps that provide automated and precision fluidic manipulations. Examples include: i) Initial progress towards an approach for investigating how cell growth relates to progression through the division cycle, and if single cell response to pathway-directed therapeutics can be classified according to subtle changes in growth. ii) Validation of a non-optical alternative for biomolecular detection where early stage aggregation is quantified by weighing each aggregate in real-time as it flows through the vibrating microchannel, and iii) A general approach for improving the performance of ligand – receptor assays based on the integration of a nanofluidic device that controllably concentrates a dilute sample and the SMR that detects specific biomarkers within the concentrate. Since the amplification (or gain) of the concentrator is adjustable, the dynamic range and detection limit of the immunoassay can be governed by the properties of the concentrator and not the binding affinity constant.
5:00 PM - FF5.7
Integration of Nanomechanical Resonators in Lab-on-a-chip Systems for Specific Protein Detection.
Wooree Ko 1 2 , Christopher Backhouse 1 , Stephane Evoy 1 2
1 Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada, 2 , National Institute for Nanotechnology , Edmonton , Alberta, Canada
Show AbstractNanomechanical resonators have demonstrated the ability of highly sensitive label-free detection by transducing the mass of bound analytes into resonant frequency shifts. Such a transducing mechanism can be used for early disease detection of biomolecules when applied in medical diagnostics. Zeptogram level and even single molecule detections have been successfully achieved by other research groups. Currently, most of nanomechanical resonator based sensors uses a large amount of analyte through traditional “dip-and-dry” method. These are not readily amenable to automation and prone to contamination and inter-run variation due to frequent exposure to air. Integration of nanomechanical resonators into a microfluidic system facilitates sample delivery and provides a stable Lab-on-a-chip (LOC) system that could be used routinely for diagnostic tests. Recently, microfluidic encapsulated nanoresonators have been demonstrated by Aubin et al. with samples delivered through external syringe pump attached to a fluidic system. Such an external instrumentation is bulky and, more importantly, on-chip biological sample detection has not yet been reported. Here we present a microfluidic sensor chip that encapsulates nanoresonators, delivers sample by on-chip automated micro-pneumatic pumps and valves similar to those developed by Grover et al., and detects specific biological samples. The resonators are 700nm wide, 340nm thick and 5μm to 10μm long (4MHz to 14.5MHz) fabricated on silicon-on-insulator substrates. Resonance actuation and detection have been performed in vacuum using optical interferometric setup.The impact of plane fluids on the sensor has been evaluated by monitoring the frequency shifts after flowing ethanol and DI water, followed by nitrogen dry. The resonators were resistant to stiction after the fluids. The average percent frequency shifts were 0.05 % due to DI water and 0.03 % due to ethanol. For specific protein detection, silane-functionalized resonators were treated with 5.5l of biotin and streptavidin solutions. The resulted shifts were 0.20 % due to biotin and 0.32 % due to streptavidin. For negative control, biotin solution was flowed onto non-functionalized resonators where no biotin adsorption is expected. The average resonance shift of 0.07 % was measured, and this shift is in the same order of magnitude as the shifts due to the flows of simple fluids containing no analyte molecules. By subtracting the base shift of 0.07 % from the measured shifts due to biotin and streptavidin, the detected masses are 8.6 ~ 13.2 fg of biotin and 18.1 ~ 27 fg of streptavidin, which corresponds to the surface coverage of 77 % and 62 %, respectively. We have successfully demonstrated the femtogram level detection on the nanoresonator based LOC system that is capable of automated sample delivery. We are currently working to fully evaluate the limit of detection of the device and will present the latest results at the conference.
5:15 PM - FF5.8
Nanomechanical Cantilever Sensors – A Novel Platform for Medical Diagnostics.
Joachim Koeser 1 2 , Martin Bammerlin 1 , Felice Mauro Battiston 1 , Urs Hubler 1
1 , Concentris GmbH, Basel Switzerland, 2 School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Muttenz Switzerland
Show AbstractOver recent years, nanomechanical cantilever sensors have been established as a promising novel technology platform for medical diagnostics. Coating these microfabricated beams with chemical receptors on one side of their surface turns them into highly sensitive, versatile and label-free chemical sensors or biosensors. In what is called the static operation mode, the bending of a cantilever as a consequence of an interaction at its surface is measured with nanometer resolution. This deflection is caused by surface stress, i.e. forces acting parallel to the cantilever surface and originating as a consequence of steric effects, electrostatic forces or conformational changes within the immobilized surface layer. This unique detection principle does not depend on the mass of the bound analyte and therefore has a big potential for measuring low molecular weight entities like protein ligands, enzyme substrates or ions. Measuring the resonance frequency of the cantilever sensor, which can occur in parallel to the deflection measurement, in addition provides complementary information on the adsorption or desorption of mass. The principle of cantilever sensor detection has been established e.g. for the detection of specific DNA sequences or proteins such as various biomarkers or antibodies. In the area of diagnostics, the feasibility of cantilever sensors for high-sensitivity detection of ions, fast bacterial growth monitoring in antibiotic resistance tests or even the use as an “electronic nose” for breath analysis has been demonstrated, illustrating the impressive versatility of this technology platform. With the availability of commercial tools, targeted development of biomedical assays based on nanomechanical cantilever sensors has recently become accessible to a widespread research community. In this presentation, an overview of recent results with relevance for the biomedical application of cantilever sensors will be discussed. A particular focus will be on the suitability of cantilever sensors for the investigation of analyte-membrane interactions which is demonstrated by means of studying the interaction of cholesterol with a layer of hydrophobic molecules. The last part will give a brief overview of the products and tools available for the development of new cantilever-based assays.
5:30 PM - FF5.9
Bacteriophage-derivitized Resonant Cantilevers for the Highly-specific Detection of Bacteria.
Amit Singh 1 , Glass Nick 1 , M. Tolba 2 , L. Brovko 2 , M. Griffiths 2 , S. Evoy 1
1 Electrical and Computer Engineering, National Institute for Nanotechnology, Edmonton, Alberta, Canada, 2 Canadian Research Institute for Food Safety, University of Guelph, Guelph, Ontario, Canada
Show AbstractThere is a growing interest in developing biosensors for the sensitive and specific detection of pathogenic microorganisms. Antibodies have been widely employed as probes for the specific detection of pathogens and antigens. However, they suffer from drawbacks such as cumbersome production, isolation and purification. Polyclonal antibodies are hindered by their poor stability and cross-reactivity while monoclonal antibodies offer better selectivity and specificity but are cost-ineffective. Bacteriophages are viruses that infect bacteria. These phages are highly specific to their host strains, and thus have great potential as highly-selective probes for the detection of pathogens. However, phages need to be immobilized onto the sensor surface in order to perform such capture. Simple physical adsorbtion typically results in a relatively low surface density of attached phages. Chemical binding strategies must therefore be developed to improve such coverage. We have already reported the use of the biotin-streptavidin affinity to immobilize biotinylated phages onto gold surfaces. This method requires genetic modification of the phages to express biotin on their protein capsid, limiting the versatility of the approach. Thus, there is a need to develop a simpler process that would rather leverage the natural proteins present on wild-type phages as anchor points.We have investigated several protocols aiming to perform such covalent attachment of wild-type phages onto gold surfaces. The T4 phage was chosen as the model system using E. coli EC12 strain as the host bacteria. Control experiments were performed with 3 non-host bacterial strains (E. coli 6M1N1, NP 30 and NP 10) to ensure specificity of the bacterial capture. The optimal approach consisted of using thiol chemistry to derivatize gold surfaces with cysteine and cysteamine hydrochloride followed by gluteraldehyde activation (2% v/v). This technique enabled a density of attached phage as high as 18 ± 3 phages/µm2 compared to the density of 10 ± 5 phages/µm2, obtained using genetically modified biotinlyated phages. These surfaces successfully captured the host E Coli with a density of 5 cells/100µm2 while the non-host strains showed negligible binding confirming the high specificity of the attachment.This protocol was then successfully employed for the specific detection of E Coli using resonant microcantilevers. Higher resonant bending modes (7th and 8th) were used to quantify the mass of the attached bacteria. In the case of E. coli capture, shifts of resonant frequencies associated to the bacteria capture indicated the binding of 4.85 cells/100µm2, in close agreement with the surface densities observed by fluorescence. No resonant shift was observed when the negative control strain were employed, confirming again the specificity of the detection. This approach could be employed in numerous other sensing platforms such as surface plasmon resonance and quartz-crystal microbalance.
5:45 PM - FF5.10
Million-fold Concentration of Protein in 200 Seconds with Nanopore Membrane Integrated Microfluidic Chip.
Dapeng Wu 1 , Joshua Butler 1 , Andrew Steckl 1
1 Nanoelectronics Laboratory, University of Cincinnati, Cincinnati, Ohio, United States
Show AbstractHighly efficient preconcentration is a crucial prerequisite to the identification of important protein biomarkers with extremely low abundance in target biofluids. Several approaches are being investigated utilizing microfluidic chips as the vehicle, with the goal of developing low-cost portable clinical diagnosis and environmental monitoring tools. Previous reports of microfluidic protein preconcentration indicated thousand-fold increases in several minutes using cross-linked hydrogels, silica gels or monolithic beds as the nanofilter. A million-fold concentration in ~ 1hr was also reported using an array of nanochannels as the filtering element. The critical figure of merit (FOM) for the preconcentration process is the ratio of the concentration gain (ratio of initial to final concentrations, G=Cf/Ci) and the time duration: α=G/t. We are investigating the approach based on electrofluidic filtration with nanoporous membranes. We utilize a 10 nm nanopore polycarbonate membrane sandwiched between two polydimethylsiloxane (PDMS) layers. The top and bottom channels in the PDMS chip are electrically connected via the transportation of small ions through nanopores, while large molecules or objects (proteins, DNA, cells, beads, etc.) are retained and concentrated on the membrane. We have used a novel dual cathode biasing of the sample channel in order to establish a sharp electric field gradient (“pinch” field configuration) across the corners of the membrane where the sample and buffer channels overlap. This results in protein collection within a very narrow region, which greatly enhances the ability to detect low level of fluorescence from protein indicators. The typical PDMS chip had channels that were 1 cm long, 50 µm wide and 15 µm deep. In our experiments, fluorescein labeled human serum albumin solution of 0.3 pM can be concentrated to 0.3 µM within 200 seconds, when 800 V/cm electric field was applied across the membrane. This yields the highest FOM value for protein preconcentration reported to date of α=5000/sec. By comparison, using the conventional single biasing scheme resulted in an unstable concentrated protein zone, whose location changed with time, and whose concentration gain and FOM was much less reproducible. The ~10× improvement in FOM over alternate approaches reported here indicates that sub-minute million-fold protein concentration is achievable. We believe that our results with the pinch field bias approach hold great promise for future scientific and commercial applications of microfluidic preconcentrators. The combination of rapid detection with the low fabrication cost of PDMS chips and the commercial availability of nanopore membranes is also very attractive for other types of microfluidic functional units, such as on-chip immunoassay, enzyme hydrolysis, and electrophoresis separation, and therefore, can be extended to the on-line and fast identification capability of interesting protein targets with microfluidics.
FF6: Poster Session: Nanodevices and Sensing Techniques for Biomedical Applications
Session Chairs
Sangeeta Bhatia
Anja Boisen
Larry Nagahara
Thomas Thundat
Wednesday AM, December 03, 2008
Exhibition Hall D (Hynes)
9:00 PM - FF6.1
Nano-scaled Debye Capacitive Sensors for Highly Sensitive, Label-free, Nucleic Acid Analysis.
Manu Sebastian Mannoor 1 2 , Teena James 1 2 , Dentcho Ivanov 1 2 , Bill Braunlin 3 , Les Beadling 3
1 Microlelctronics Research Center, New Jersey Institute of Technology, Newark, New Jersey, United States, 2 Dept. of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, United States, 3 , Rational Affinity Devices LLC., Newark, New Jersey, United States
Show AbstractOver a decade of rapid advances in Micro and Nano fabrication technologies has opened up enormous possibilities across various fields of science and technology. The integration of microelectronics technology with molecular biology is having a transforming impact in the development of biosensors with potential applications in future drug and diagnostic development. By the use of miniaturization techniques, the sensing elements or at least parts of them are now getting shrunk down to the same order of dimension as the bio molecules being sensed, immensely improving the detection sensitivity.Capacitive sensors provide a promising alternative to the conventional Optical methods used for detecting biomolecular interactions, due to their label-free operation, simple instrumentation and the ease of miniaturization. Although, several configurations of capacitive biosensors have been reported in the literature, many physical and electrochemical properties of these structures and the measurement methods used have significantly limited their commercial full-scale development as a biosensor. The existence of electrode polarization effect and noises from solution conductance limited the earlier dielectric spectroscopic measurements to high frequencies only, which in turn limited its sensitivity to biomolecular interactions, as the applied excitation signals were too fast for the charged macromolecules to respond. In addition, the series parasitic impedance from electrode polarization effect masked the dielectric changes occurring due to biomolecular interactions at low frequencies (<1 kHz) further reducing the detection sensitivity.In an attempt to address the above mentioned challenges, we report a NEMS capacitive sensor with electrode separation of 20nm (<< Debye length). This nano-scale sensing area provides better insight into the molecular interactions, which was not previously attainable with macro or even micro scale devices. The interaction between the electrical double layers due to the space confinement decreases the potential drop across the electrode spacing and allows dielectric measurements at low frequency. As the double layers from both the capacitive electrodes merge together and occupy a major fraction of the capacitive volume, the contribution from bulk sample resistance in the measured impedance is eliminated. The dielectric properties during hybridization reaction were measured using 10-mer nucleotide sequences. A 45-50% change in capacitance was observed due to DNA hybridization at 10Hz. The use of SiO2 sacrificial layer process allowed to overcome the resolution limit of conventional lithographic techniques and the desired separation of 20nm between the Gold electrodes were attained. The improved sensitivity and selectivity of the Debye Capacitive sensor combined with the use of reduced sample volume and low fabrication cost are promising for applications such as point of care diagnostics and bio-warfare agent detection.
9:00 PM - FF6.10
Nanoparticle-based Antimicrobial Photochemotherapy.
Carla Fontana 1 2 , Judy Chen 3 , Harikrishna Devalapally 4 , Karriann Ruggiero 2 , Xiaoqing Song 2 , Joshua Dunham 2 , Ziedonis Skobe 5 , Tom Pagonis 3 , Mansoor Amiji 4 , Nikolaos Soukos 2
1 Grupo de Optica , Instituto de Física USP Sao Carlos , Sao Carlos , Sao Paulo, Brazil, 2 Applied Molecular Photomedicine Laboratory, The Forsyth Institute, Boston, Massachusetts, United States, 3 Division of Endodontics, Harvard School of Dental Medicine, Boston, Massachusetts, United States, 4 Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States, 5 Department of Biostatistics and Biostructure Core Facility/Department of Biomineralization, The Forsyth Institute, Boston, Massachusetts, United States
Show AbstractPhotodynamic therapy (PDT), the synergistic effect of light and a photoactive drug known as photosensitizer (PS), has been suggested as an alternative to chemical antimicrobial agents to eliminate bacterial species. Here we used FDA-approved polymeric nanoparticles of polyb(lactic-co-glycolic acid) (PLGA) as a delivery system for the PS methylene blue (MB) for phototargeting Enterococcus faecalis, a pathogen associated with failures of endodontic treatment, in vitro. The uptake and distribution in E. faecalis was investigated by transmission electron microscopy (TEM) after incubation with PLGA complexed with colloidal gold particles for 2.5, 5 and 10 min. A large fraction (>99%) of nanoparticles were found to be concentrated onto the cell walls of microorganisms at all three time points. Sensitization of E. faecalis species in planktonic phase with MB-loaded nanoparticles for 10 minutes followed by exposure to red light at 665 nm led to approximately 2 log10 reduction of colony-forming units. Methylene blue-loaded nanoparticles in combination with red light eliminated approximately 1 log10 of E. faecalis biofilm bacteria in experimentally infected root canals of human extracted teeth. The data suggest that PLGA nanoparticles encapsulated with photoactive drugs may have an application in oral antimicrobial photodynamic therapy.
9:00 PM - FF6.11
Development of Novel Multifunctional Nanoparticles for Targeted Delivery of Concurrent Chemoradiotherapy.
Kai Yuet 1 , Andrew Wang 2 3 , Liangfang Zhang 1 2 , Frank Gu 1 2 , Minh Huynh-Le 1 , Robert Langer 1 2 , Omid Farokhzad 2 4
1 Department of Chemical Engineering, MIT, Cambridge, Massachusetts, United States, 2 Harvard-MIT Center for Cancer Nanotechnology, MIT, Cambridge, Massachusetts, United States, 3 Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States, 4 Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
Show AbstractCancer is the second leading cause of death in the United States. In general, contemporary cancer therapies involve surgery, chemotherapy and radiation therapy. The concurrent administration of both chemotherapy and radiotherapy significantly improves survival as compared to sequential administration in many different cancers. This practice has become the standard of care for rectal, head and neck, lung, gastric, cervical, pancreatic and esophageal cancers. Despite enhanced organ preservation and survival rates, concurrent chemoradiotherapy leads to much higher toxicity. Therapeutic nanoparticle delivery systems such as Doxil and Abraxane have been shown to both increase the efficacy and decrease the toxicity of chemotherapy in relation to their small molecule counterparts. We hypothesized that a nanoparticle platform that can deliver both chemotherapy and radiotherapy can improve efficacy and lower toxicity of chemoradiotherapy. Here we report the development of a novel multifunctional nanoparticle delivery system for targeting of concurrent chemoradiotherapy to prostate cancer cells. We fabricated the nanoparticles by nanoprecipitation of the copolymer poly(lactic-co-glycolic acid) (PLGA) in an aqueous solution containing the phospholipids lecithin, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol 2000 (DSPE-PEG) and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine diethylene triamine pentaacetatic acid (DMPE-DTPA). Following nanoprecipitation, a protective lipid monolayer self-assembles around the polymeric nanoparticle due to hydrophobic interactions between PLGA and the non-polar fatty acid tails of the phospholipids. These lipid-polymer nanoparticles have a hydrodynamic diameter of 70+/-5 nm and a zeta potential of -40+/-5 mV. In addition, these nanoparticles both chelate metal radioisotopes with DMPE-DTPA and encapsulate chemotherapeutic agents in its PLGA core. We demonstrated that the nanoparticles release docetaxel according to first order kinetics and indium-111 according to zeroth order kinetics in seven day release studies. The nanoparticles exhibited very high chelation efficiency, binding 99+/-0.3% of their initial radiometal load, and do not release any of their chelate within the first 36 hours, and 50% after 120 hours. Furthermore, using prostate cancer as a model, we showed that the nanoparticles targeted to cancer cells and enhanced intracellular uptake when functionalized with the A10 RNA aptamer that binds to the prostate-specific membrane antigen (PSMA). LNCaP (PSMA+) prostate adenocarcinoma cells incubated with NBD cholesterol-encapsulated nanoparticles showed much higher fluorescence than their PSMA- complements, PC3 cells. Similarly, LNCaP cells incubated with indium-111-chelated nanoparticles showed much higher radioactivity than PC3 cells. To our knowledge, this study represents the first report of targeted delivery of concurrent chemoradiotherapy with a multifunctional nanoparticle platform.
9:00 PM - FF6.12
Monitoring of Apoptosis and Necrosis by Capacitance Measurements.
Rimi Lee 2 , Sooin Yeon 3 , Hyangtae Choi 4 , Kun hong Kim 2 4 , Jeon-soo Shin 2 3 , Kyung-Hwa Yoo 1 2
2 Nanomedical National Core Research Center , Yonsei university, seoul Korea (the Republic of), 3 Department of Microbiology, Yonsei University College of Medicine, Yonsei university, seoul Korea (the Republic of), 4 Department of Biochemistry and Molecular Biology, Yonsei university, seoul Korea (the Republic of), 1 Physics, Yonsei University , Seoul Korea (the Republic of)
Show AbstractApoptosis and necrosis are two different paths for cell death. One of differences between apoptosis and necrosis is the cell morphology. Apoptotic cells shrink without loosing the integrity of their plasma membrane and break into smaller pieces called apoptotic bodies that macrophage cells recognize and engulf them. In contrast, necrotic cells swell and their plasma membrane eventually ruptures. Since the cell membrane is closely related to the capacitance (or dielectric constant), we have fabricated a capacitance sensor, which can measure the capacitance of 1~4 cells, and investigated its time dependence during apoptosis and necrosis for TE2 cells induced by TNF related apoptosis inducing ligand (TRAIL) and ethanol. The capacitance decreases monotonically during apoptosis. For necrosis, however, step-like behaviors are observed and dips are found in the dC/dt-t curves. The time-lapse images of TE2 cells, which have been taken simultaneously with the capacitance measurements, show that dips in the dC/dt-t curves are probably due to the rupture of cell membrane. These results suggest that apoptosis and necrosis may be differentiated by the capacitance measurements.
9:00 PM - FF6.13
Poly(3-hydroxybutyrate) Nanoparticle as a Smart Carrier for Drug Delivery System.
Han-nah Kim 1 , Jin Lee 1 , Young-rok Kim 1
1 Department of Food Science and Technology, Kyung-hee University, Yongin Korea (the Republic of)
Show AbstractIn this study, we demonstrated a facile method to prepare polyhydroxybutyrate (PHB) nanoparticle with enhanced functionality as a smart carrier materials. PHB is an aliphatic polyester intracellularly accumulated as carbon and energy sources in numerous microorganisms. PHB is a good candidate for drug delivery materials because this polymer is biocompatible and completely degraded to CO2 and H2O in biological environments. PHB synthase is the key enzyme and used to produce PHB nanoparticles in PHB biosynthesis. PHB synthase from Ralstonia eutropha H16 was expressed from recombinant Escherichia coli and purified. The purified PHB synthase and substrate, 3-(R)-hydroxybutyryl-Coenzyme A, are subsequently used to synthesize PHB particles in vitro. Activities of PHA synthase on various substrate concentrations are determined by Ellman’s assay. Biosynthesized nanoparticles were compared with PHB microspheres prepared by conventional oil-in-water emulsion-solvent evaporation method. For the conventional emulsion method, PHB polymer from Ralstonia eutropha H16 was extracted and dissolved in an organic phase and then emulsified in an aqueous solution containing a stabilizing agent. After evaporation of the organic solvent, microspheres were obtained. Size and shape of the resulting particles are analyzed by dynamic light scattering, fluorescent microscope and field emission scanning electron microscope (FE-SEM). Sub-micron sized PHB particles, ranges from 200 nm to 900 nm, were successfully synthesized by simple enzymatic reaction containing substrate and enzyme. The resulting PHB particles are relatively uniform in size and shape as compared with particles prepared by emulsion method. The size of biosynthesized PHB particles can be controlled by concentration of the enzyme. During the polymerization reaction, PHB synthase attached to the polymers as dimeric forms and synthesized PHBs are aliphatic polyesters forming inside parts of the particles. Consequently, protein-PHB hybrid material is obtained and this formation gives particles the stability, functionality and amphiphilic character. Through this study, we demonstrated the potential of this material to be developed to a smart delivery system by introducing a specific receptors or ligands to the surface of particles by protein engineering.
9:00 PM - FF6.14
Gold Nanoparticles Coated by PEG with Thioctic Amides Terminal: Their Features in vitro and Fates in Tumor-xenografted Mice.
Guodong Zhang 1 , Wei Lu 1 , Rui Zhang 1 , Zhi Yang 1 , Qian Huang 1 , Chun Li 1
1 Experimental diagnostic Imaging, University of Texas MD anderson Cancer Center, Houston, Texas, United States
Show AbstractPEG coated gold nanoparticles are intensively being developed for biomedical applications including drug delivery vehicles and new diagnostic imaging agents. In this work, the effects of PEG structures, including anchoring ligands, molecular weight, and size of gold nanoparticles on the physicochemical properties and stabilities in vitro of PEG-coated gold nanoparticles are investigated. It was revealed that there seems to be a curvature dependence to coat same PEG containing thio or thioctic acid terminals on different size of gold nanoparticles. PEG coated gold nanoparticles, based on thioctic amid terminals as anchoring ligands, exhibited apparently improved stability in PBS with DTT, compared to analogs prepared from PEG with monothio terminal. With 111Indium chelated in DTPA as a radioactive marker, immobilized on the surface of gold nanoparticle, the promising PEG5000-TA coated gold nanoparticles with various sizes were further tested in nude mice bearing subcutaneous human A431 xenografts to elucidate their in vivo pharmacological profiles. PEG5000-TA coated 20 nm gold nanoparticles exhibit relatively extended blood circulation times and moderate uptake by the reticuloendothelial system. Significantly, PEG5000-TA coated 20 nm gold nanoparticle shows a high tumor accumulation, and an ability of penetrating the tumor tissue and internalizing into the tumor cells. Thus, the 20 nm gold nanoparticles coated by PEG5000-TA is excellent candidates for diagnostic imaging agents and drug delivery vehicles to tumor.
9:00 PM - FF6.15
Advanced Functional Graphite-Coated Magnetic Nanoparticles as RF Thermal Ablation Agents for Cancer Therapies.
Yang Xu 1 , Meena Mahmood 1 , Zhongrui Li 1 , Enkeleda Dervishi 1 , Steve Trigwell 2 , Vladimir Zharov 3 , Nawab Ali 1 , Viney Saini 1 , Alexandru Biris 4 , Dan Lupu 4 , Alexandru Biris 4
1 , University of arkansas at little rock, Little rock, Arkansas, United States, 2 , NASA, ASRC Aerospace, , Kennedy Space Center,, Florida, United States, 3 , Philips Classic Laser Laboratories, Little rock, Arkansas, United States, 4 , National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj Napoca Romania
Show AbstractGraphitic shells coated ferromagnetic cobalt nanoparticles (C-Co-NPs) with diameters of around 7-9 nm cubic crystalline structures were synthesized by catalytic chemical vapor deposition (CCVD). X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis indicated that the Co-NPs inside the carbon shells were preserved in the metallic state. Confocal microscope images revealed effective penetrations of C-Co-NPs through plasmatic membranes into the nucleus of the cultured HeLa cancerous cells. Low RF radiation of 350 kHz triggered the cell death, process that was found to be dependent on the NPs concentration and application time. Compared to carbon nanostructures such as single wall carbon nanotubes, super paramagnetic cobalt nanoparticles demonstrated higher specificity for RF absorption and heating. For the first time we reported that DNA fragmentation assay after the RF treatment showed a strong broadening of the DNA gel electrophoresis spectrum, which further proved nucleus disintegration under RF exposure. This work indicates a great potential of a new technology for tumor thermal ablation.
9:00 PM - FF6.17
Nanostructured and Bulk GaN & InN Transducers in Electrochemical Sensors & Biosensors.
Nikoletta Sofikiti 1 , J. Grandal 2 , M. Utrera 2 , M. Sanchez-Garcia 2 , E. Calleja 2 , N. Chaniotakis 1
1 Laboratory of Analytical Chemistry, Department of Chemistry, University of Crete, Iraklion Greece, 2 ISOM and Departamento de Ingenieria Electronica, ETSI Telecomunicacion Univ. Politecnica de Madrid, Madrid Spain
Show AbstractIn this presentation, we will show very recent results from our efforts to utilize nanostructured GaN & InN as sensing elements and transducers, and provide pertinent methodologies and data on how these materials can be successfully employed for the development of novel chemical sensors and biosensors. More specifically, our results indicate that these two materials (c-plane GaN & InN, Ga and In face respectively) show similar pH and anionic (Cl-) potentiometric response when they are in bulk form. Interestingly, though, both of these materials lose a big part of their anionic sensitivity when in nanostructured (nanocolumns) form, while on the contrary they maintain their pH sensitivity almost intact. These results indicate that the anionic potentiometric response of these materials is closely related with the crystal orientation, as has been previously shown for GaN, since the observed sensitivity is due to the direct interaction of the Lewis basic anions with the Lewis acidic gallium or indium atoms of the surface which act as the fixed sites for the specific and reversible anion coordination. This actually seems to be the main reason for this intense reduction of the anionic sensitivity of these materials when they are in nanostructured form, because in this form the crystal orientation homogeneity of the material’s surface is intensively disturbed. On the contrary, our results indicate that the pH sensitivity of these materials is almost completely irrelevant with the crystal orientation of the material, since the pH sensitivity seems to be due to, not only the direct and specific interaction of the Lewis basic hydroxide anions of the solution with the Lewis acidic gallium or indium atoms of the surface, but also due to hydrogen ion interaction with the generated hydroxide sites on the native surface, as has been previously shown in the case of GaN.Based on these results, we thought to investigate the possible use of these materials (in both bulk and nanostructured form), as sensing elements and transducers for the development of novel urea potentiometric biosensors. The development of these urea biosensors was based on the following enzymatic reaction:NH2CONH2 + 3H2O → NH4+ + HCO3- + OH-The Urease enzyme was physically adsorbed on the GaN and InN surfaces and the urea detection was accomplished by exploiting the pH sensitivity of these surfaces.The obtained results show that both GaN & InN surfaces can be utilized for the development of such potentiometric biosensors, but only when they are in nanostructured form they maintain their enzymatic activity for a significant period of time (a week or so). This fact indicates that the extended total surface area of the nanostructured form is of great importance for the enzyme stabilization and thus for the lifetime of the biosensor.
9:00 PM - FF6.19
Erythrocyte Deformation and Protein Folding Response of Magnetically Controllable Temperature Responsive PEG Nano-spheres for Sustained Release and Hyperthermia.
Santaneel Ghosh 1 , Tong Cai 2 , Somesree GhoshMitra 3 4 , Zhibing Hu 2 , Nathaniel Mills 3
1 Physics and Engineering Physics, Southeast Missouri State University, Cape Girardeau, Missouri, United States, 2 Department of Physics, University of North Texas, Denton, Texas, United States, 3 Department of Biology, Texas Womans University, Denton, Texas, United States, 4 Department of Microbiology and Immunology, R. G. Kar Medical College, Calcutta India
Show AbstractThermo-responsive, magnetically tunable nano-scale polymeric structures are the center of research emphasis for several potential advantages over other bio-material systems to achieve precise control, fast response and guided delivery. The nano-magnet induced heating can be controlled intrinsically by changing the size and concentration of particles or extrinsically by modifying the frequency of the magnetic field. Therefore, this system may be used to provide precise control of temperature for hyperthermia or tissue hypoxia conditions. After intravenous administration, commonly encountered problems are hemolytic effect and embolic threat due to coagulation. However, biocompatible, multifunctional systems can be designed for temperature control in combination with drug delivery and magnetic force based immunoassays [1]. The present work highlights on a novel, magnetic polyethylene glycol (MPEG) encapsulated thermo-responsive system induced response on erythrocytes. Potential hemolytic effect and globin conformational change were monitored under simulated hyperthermia. This innovative application has led to a fast-responsive, hydrogel system consisting of all FDA-approved bio-materials. The broad LCST range and localized temperature regulation of the system (28-42C) is particularly attractive for long circulation and sustained release inside the body at physiological temperatures. Magnetic PEG synthesis involves optimization of particle content, size and polymer concentration. Precise temperature regulation is achieved under a smaller magnetic field, keeping the volumetric shrinkage unaffected. Low residual magnetism (0.298 x 10-3 emu/gm) of the system prevents agglomeration after repeated heating. Surface functionalization of the system allows target specific concentration enhancement. Lysis of RBC membrane and induced deformity effects were monitored by optical and electron microscopy for EDTA mixed blood with selected concentration of MPEG after oscillating field exposure (0-4 days, 30 min; 6 kA/m, 120 kHz). From the micrographs, there was no evidence of lytic effect or deformity upto moderate concentration (15mg/mL), but at higher concentration (25mg/mL), induced deformity was observed. Native-PAGE gel eletrophoresis was performed to asses any possible change in hemoglobin folding as unfolding affects the oxygen carrying capacity. Preliminary results show that the previously reported safe limit and exposure time, there was no change in globin folding structure compared to control. Considering intravenous administration renders 100% bioavailability combined with required concentration ranges in target tissues, this finding excludes the possibility of hemolytic anaemia i.e. direct hemolysis by PEG based system and phagocytosis of deformed RBC’s by macrophages in spleen. Effects on coagulation cascade is in progress to determine the potential threat of thromboembolism. [1] Dobrovolskaia, M., et.al, Nature, 2, 2007, 469.
9:00 PM - FF6.2
DNA Hybridization Detection using ZnSe Nanocrystals as Active Sensors.
Jun Wang 1 , Tracy Heckler 1 , Bing Mei 1 , Pedro Lei 2 , Stelios Andreadis 2 , T Mountziaris 1
1 Chemical Engineering, University of Massachusetts, Amherst, Massachusetts, United States, 2 Chemical and Biological Engineering, University at Buffalo - SUNY, Amherst, New York, United States
Show AbstractFluorescent labeling of biological molecules is used widely for analytical purposes in biotechnology and bioengineering. It typically involves the use of an organic dye linked to a moiety that selectively bonds a particular biological molecule, allowing the detection of the latter by the fluorescence of the dye. Typical organic fluorescent dyes have narrow excitation spectra and broad emission spectra that exhibit red tailing. Semiconductor nanocrystals or quantum dots have emerged as a new class of fluorescent markers with distinct advantages over the traditional organic dyes [1-3]. Their attractive properties include a narrow, symmetric, and strong emission that is size-tunable, continuous excitation by any wavelength smaller than the emission wavelength, resistance to photobleaching, as well as excellent optical and chemical stability that allows their use in lengthy experiments, both in vitro and in vivo. The ability to synthesize different populations of quantum dots with narrow emission spectra permits multiplexing, a property that is very important for simultaneous detection of several analytes, that would be very tedious and expensive if done sequentially. In addition to their use as multi-color "passive" tags for biomolecules, quantum dots have significant potential as "active" sensors, because their optical spectra change when the detection molecules attached to their surface hybridize with complementary ones in solution. The focus of this work is the development of new biological detection and DNA analysis schemes by using the changes in the optical spectra of ZnSe quantum dots. We have synthesized highly-fluorescent ZnSe quantum dots, modified their surface with functional molecules to render them water-dispersible, and conjugated them with oligonucleotides. Hybridization of complementary oligonucleotides conjugated with ZnSe quantum dots results in a significant increase in the fluorescence intensity of the quantum dots and a measurable red shift in the emission wavelength. A series of experiments was performed in which DNA hybridization was studied using ZnSe quantum dots conjugated with oligonucleotides as active sensors and free oligonucleotides in solution as targets. An increase in the emission intensity of the quantum dots was observed upon hybridization of the tagged oligonucleotides with free oligonucleotides. A dependence of the detected fluorescence emission intensity on the length and location of the hybridized part was detected, indicating that spectral changes can be used to identify the DNA structures attached to the quantum dots. Ongoing experiments focus on determining the sensitivity of this technique for detecting DNA mutations. Applications of these phenomena in the development of novel DNA analysis strategies will be discussed. References 1. M. Bruchez, et al., Science 281, 2013 (1998). 2. W.C.W. Chan and S. Nie, Science 281, 2016 (1998). 3. M.-Y. Han, et al., Nature Biotechnology 19, 631 (2001).
9:00 PM - FF6.20
Room Temperature Transcutaneous CO2 Detection Using TiO2 Nanotube Arrays.
Thomas LaTempa 1 2 , Somnath Roy 2 , Oomman Varghese 2 , Craig Grimes 1 2 3
1 Electrical Engineering, The Pennsylvania State University, University Park, Pennsylvania, United States, 2 , Materials Research Institute, University Park, Pennsylvania, United States, 3 Materials Science and Engineering, Pennsylvania State , University Park, Pennsylvania, United States
Show AbstractHighly ordered, vertically oriented titania nanotube arrays fabricated via potentiostatic anodization have been developed for room-temperature, transcutaneous carbon dioxide detection. Previously, titania nanotube arrays have been investigated for localized drug delivery in antibiotic-loaded titania bone implants [1] and transcutaneous hydrogen sensing for medical diagnostics [2]. Hydrogen sensors based on nanotubular titania arrays show unprecedented sensitivity; changes in electrical resistance of 8.7 orders of magnitude have been observed when cycled with 1000 ppm of hydrogen at room temperature. These devices are characterized by large sensitivity, fast response time and no hysteresis. Currently no semiconductor-based CO2 sensors exist that operate at room temperature. We are developing room temperature hydrogen and CO2 sensors for early diagnosis of acidosis and necrotizing enterocolitis (NEC). Transcutaneous detection provides a quick, non-invasive method to diagnose these diseases. CO2 sensitivity is achieved through surface functionalization of the nanotube arrays with calcium ions and subsequent annealing to form a layer of calcium oxide along the length of the nanotube walls. Exposure to carbon dioxide causes a change in electrical resistance which is correlated to CO2 levels in the patients’ blood stream. 1 μm nanotube arrays were immersed overnight in a methanolic solution of calcium acetate containing 25 % water and subsequently annealed in oxygen at 150 deg C. Sensors fabricated using these calcium oxide coated nanotubes exhibited a change in resistance of 1 MΩ from 15.6 MΩ to 14.6 MΩ on exposure to 25% CO2. Efforts are underway to enhance the sensitivity of the carbon dioxide sensors. The results of modifying the nanotube geometry and methods to functionalize the surface will be discussed. Clinical studies with Hershey Medical Center in Hershey, PA are currently underway and the findings of these studies will be presented as well. [1]Popat, K. C.; Eltgroth, M.; LaTempa, T. J.; Grimes, C. A.; Desai, T. A., Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes. Biomaterials 2007, 28, (32), 4880-4888.[2]Varghese, O. K.; Yang, X. P.; Kendig, J.; Paulose, M.; Zeng, K. F.; Palmer, C.; Ong, K. G.; Grimes, C. A., A transcutaneous hydrogen sensor: From design to application. Sensor Letters 2006, 4, (2), 120-128.
9:00 PM - FF6.21
Gold Nanorod-modified Substrates for Localized Plasmon Resonance Sensing of Biomolecules.
Yasuro Niidome 1 , Kanako Honda 2 , Yukichi Nakamura 1 , Naotoshi Nakashima 1
1 Department of Applied Chemistry, Kyushu University, Fukuoka, Fukuoka, Japan, 2 Department of Biological and Environmental Chemistry, Kinki University, Iizuka, Fukuoka, Japan
Show AbstractGold nanorods (GNRs) are rod-shaped gold nanoparticles showing localized surface plasmon (SP) bands in visible and near infrared (near-IR) regions. The peak positions of the longitudinal SP bands are sensitive to refractive indices just around the GNRs. Thus, the GNRs have been expected as a probe material for localized SP resonance (LPR) sensing. Previous papers reported small peak shifts (< 40 nm) of the SP bands depending on the local indices, even when a glass substrate, on which GNRs were fixed, was immersed in some kinds of solvents.[1] In this work, we prepared sensitive GNRs to adsorption of biorelated molecules. The GNRs were fixed on a glass substrate through electrostatic interactions.[2] Their spectroscopic properties, which were obtained by a conventional spectrophotometer, showed typical double SP bands of GNRs. Thus, the GNRs were fixed on the substrate without forming aggregates. Scanning electron microscopic observation also indicated that isolated GNRs were fixed on the glass surface. On the surfaces of the GNRs, antibodies (rabbit IgG anti-human prostate specific antigen (PSA)) were attached, and then the substrate was immersed in a PSA solution. The longitudinal SP bands of the GNRs shifted about 70 nm to longer wavelength regions after the attachment of the antibodies. In addition, the SP bands were further red-shifted by immersion in the PSA solutions. The maximal red-shift from the antibody-modified GNRs was 35 nm; this shift was obtained when the substrate was immersed in a 1 ng/L of PSA solution. When a 0.1 ng/L PSA solution was used for the immersion, the red-shift of the GNRs was about 5 nm. It was shown that the GNR-modified substrate could be used for LPR sensing of biomolecules with sufficient sensitivities for practical applications.1.Niidome, Y.; Takahashi, H.; Urakawa, S.; Nishioka, K.; Yamada, S., Chem. Lett. 2004, 33, 454.2.Honda, K.; Niidome, Y.; Nakashima, N.; Kawazumi, H.; Yamada, S., Chem. Lett. 2006, 35, 852.
9:00 PM - FF6.22
Gap-tunable Au Nanoparticles in Insulating Matrix: Topological Analysis and Application in Plasmonic Nanosensors.
Shuyan Gao 1 , Naoto Koshizaki 1 , Emiko Koyama 1 , Hideo Tokuhisa 1 , Kazuhiro Kirihara 1 , Takeshi Sasaki 1 , Yoshiki Shimizu 1 , Deok-Soo Kim 2
1 , Nanotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan, 2 , Department of Industrial Engineering, Hanyang University, Seoul Korea (the Republic of)
Show Abstract9:00 PM - FF6.23
Microelectrodes-Assisted Micropatterning on Nanofiber.
Hansong Zeng 1 , Feng Wang 2 , Jianjun Guan 2 , Yi Zhao 1
1 Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States, 2 Material Science and Engineering, The Ohio State University, Columbus, Ohio, United States
Show AbstractRecently, there is a growing interest in nanoscale polymer fibers due to their unique mechanical, optical, electrical properties, biocompatiblility and porous structures. Particularly, nanofibers have gained extraordinary attention in tissue engineering, drug delivery, molecular electronics and optics. Advances in research have shown increasing evidences that integration of nanostructures and microstructures are important. For instance, it was found that direct osteoblast (bone-forming cells) adhesion and deposition of calcium phosphate tend to occur on micropatterns of carbon nanofibers. Micropatterned poly-caprolactone (PCL) scaffolds with nanoscale pores can induce vascular smooth muscle cells (VSMC) alignment and promote nutrient diffusion through the nano-pores, which is similar to natural human vessels. All these work indicate the importance of integrating microscale topographies into nanostructured materials for biomedical applications. In this work, we described a method to fabricate micropatterned nanofibers by electrospinning polymeric solutions on a glass surface patterned with microelectrodes. In the process, the microelectrodes served as the collector and were electrically connected to the ground. When the positively charged nanofibers got close to the surface, negative charges were induced on the conductive portion of the surface, i.e. the metal electrodes, while the insulating glass surface was electrically neutral. In response to the electrostatic force, positively charged nanofibers have more chance to be whipped on the surface of the electrodes than on the glass. This was confirmed by the SEM picture showing a large number of nanofibers on the electrodes in the initial phase of electrospinning. This enables the fabrication of micropatterns made of the nanofibers. As the elctrospinning proceeds, 3D topographies were observed on both sides of the nanofiber mat. The results showed that the nanofibers patterned on microelectrodes and glass are manifested by different thicknesses, porosities and densities. The nanofibers on the electrodes have larger thicknesses. The thickness difference, which contributes to the 3D topography of the nanofiber mat, is a function of the electrospinning time. The porosity correlates to the density and thickness, and has a small value at the areas of microelectrodes. An immediate application of such materials is 3D cell culture, where the micropatterned nanofibers can be applied as cell culture scaffolds. The 3D topography of such structures is expected to enhance the cell alignment and adhesion, while the porous nanofibers ensure nutrient diffusion.
9:00 PM - FF6.24
Improving SERS Detection using Membrane Encapsulated Noble Metal Nanostructures.
Kyungtag Ryu 1 2 , Maryuri Roca 1 , Hoeil Chung 2 , Amanda Haes 1
1 Chemistry, University of Iowa, Iowa City, Iowa, United States, 2 Chemistry, Hanyang University, Seoul Korea (the Republic of)
Show Abstract9:00 PM - FF6.25
Influences on the Separation of Neurotransmitters in the Presence of Covaently-Functionalized Nanoparticles.
Michael Ivanov 1
1 Chemistry, University of Iowa, Iowa City , Iowa, United States
Show AbstractThe inclusion of nanoparticles in capillary electrophoresis experiments has been shown to improve detection of analytes, facilitate the separation of nanoparticles themselves, and dramatically improve the resolution of target analytes. Despite these advances, surprisingly little research has been performed that correlates separation performance to nanoparticle attributes such as surface chemistry and degree of aggregation to separation efficiency. In this work, we will demonstrate novel capillary electrophoresis-based separations in which nanoparticles have been used to improve the separation and detection of three neurotransmitters: dopamine, epinephrine, and pyrocatechol. The degree of electroosmotic flow, nanoparticle stability, and nanoparticle surface chemistry play important roles in the separation of the neurotransmitters. Specifically, by covalently functionalizing gold nanoparticles with varying terminal groups, we will reveal that the effective charge at the nanoparticle surface can either speed or slow neurotransmitter mobility. In all cases, the stability of the nanostructures within the capillary dominates changes in neurotransmitter mobility and resolution.
9:00 PM - FF6.26
Adverse Effects of Titanium Dioxide Nanoparticles on Human Dermal Fibroblasts and How to Protect Cells.
Zhi Pan 1 , Wilson Lee 1 , Lenny Slutsky 1 , Richard Clark 2 , Nadine Pernodet 1 , Miriam Rafailovich 1
1 Materials Science & Engineering, SUNY at Stony Brook, Stony Brook, New York, United States, 2 Biomedical Engineering, Dermatology and Medicine, SUNY at Stony Brook, Stony Brook, New York, United States
Show AbstractTiO2 nanoparticles are known to be powerful photocatalysts applied in antibacterial applications and solar power cells. Yet, despite their activity, these particles are also commonly used in many consumer products ranging from paint, food colorant to cosmetics and drugs. Here, we study the interactions of different types of TiO2 nanoparticles, rutile and anatase, with primary cultured human dermal fibroblasts. We show the manner of particle penetration, sequestration, and the influence on cell functions. In all cases we find that these particles, even at relatively low concentrations, have profound effects on fibroblast proliferation and ability to exert traction forces, migrate, and contract collagen. In previous study, we showed how the photocatalytic activity of these particles can be suppressed by grafting of a dense polymer brush. Here we further study the influence of this brush on the interaction of the particles with cells. We find that the brush prevents the particles from adhering to the cell membrane and hence penetrating the cell, and that the coated particles have minimal impact on the normal cell functions. The particles are processed using polymers which comply with the industry GRAS standard and hence can easily be substituted for the bare particles in consumer products. The impact of this study is significant, since it demonstrates that there is a cause for concern and further in-vivo investigation of the toxicology of these particles and that the possibility of engineering different types of coatings can greatly improve the safety of their implementation.
9:00 PM - FF6.27
A Quantitative Description of Absolute Endocytosis and Exocytosis Rates for Nanoparticles.
Hong Jin 1 , Daniel Heller 1 , Richa Sharma 1 , Michael Strano 1
1 Chemical Engineering, MIT, Cambridge, Massachusetts, United States
Show Abstract9:00 PM - FF6.28
Prodrug Surface Incorporation onto Silicon Nanowires: Impact on Calcification and Cell Proliferation.
Jeffery Coffer 1 , Ke Jiang 1 , Dongmei Fan 1 , Jean-Luc Montchamp 1 , Yamina Belabassi 1 , Giridhar Akkaraju 2
1 Chemistry, Texas Christian University, Fort Worth, Texas, United States, 2 Biology, Texas Christian University, Fort Worth, Texas, United States
Show Abstract Semiconductor nanowires (NWs) such as those of silicon (Si) are being extensively investigated for their value in diagnostic biosensing. Yet for such materials, little information has been gleamed regarding their possible therapeutic benefit as a stand-alone platform or as a drug delivery vehicle. Given the size and surface chemical tunability of silicon nanowires, it is logical to engage in a systematic approach to evaluate their relevance in this type of application. In this presentation, the deliberate surface modification of silicon nanowires (Si NWs), including biomineralization and prodrug surface incorporation, along with the role of such effects on their interactions in vitro, are reported. In terms of specific approaches relevant to orthopedic applications, we quantitatively investigate the role of bias-induced calcium ion surface enrichment of a given nanowire in simulated plasma on acellular calcification, followed by prodrug attachment with selected bisphosphonates. This family of drugs, such as well-known alendronate, are appropriate targets for coupling to the modified nanowire surface given their widespread use for the treatment of a variety of bone diseases, including tumor-induced hypercalcemia, Paget’s disease, and osteoporosis. To further investigate biocompatiblity, proliferation assays of these modified nanowires were carried out using an orthopedically relevant cell line, meschenymal stem cells derived from mouse stroma; such cells can differentiate into osteoblasts, chondrocytes, and adipocytes under the appropriate stimulus & environment and hence are a relevant model to orthopedic tissue engineering. The long-term strategy is to produce a platform of diverse relevant electroactive scaffolds with ‘tunable’ properties that can be controlled not only by the intrinsic properties of the semiconductor present but also by its surface chemical composition.
9:00 PM - FF6.29
Model Method for Fingerprinting of Nanotoxicity of Nanoparticles using Vesicle as a Mimic for Cell Membranes.
Junsu Park 1 , Jongheop Yi 2 , Younghun Kim 1
1 Chemical Engineering, Kwangwoon University, Seoul Korea (the Republic of), 2 Chemical and Biological Engineering, Seoul National University, Seoul Korea (the Republic of)
Show Abstract9:00 PM - FF6.3
Impedance-sensing Assay for Early Detection and Recovery of Cardiomyocyte Apoptosis.
Yiling Qiu 1 , Xin Zhang 1
1 Mechanical Engineering, Boston University, Boston, Massachusetts, United States
Show AbstractCardiomyocyte apoptosis can lead to various cardiovascular diseases because it courses irreversible cardiomyocyte loss due to the very limited regeneration capability of adult hearts. Though enzymatic DNA fragmentation is most commonly used criteria of apoptosis at the level of individual cardiomyocytes, the capability of detecting cell detachment will provide instant information at early phase of apoptosis. Furthermore, the assays used to detect DNA fragmentation are all invasive to living cells, which disables real-time monitoring of the whole process. In this work, we developed an impedance-sensing assay for early detection and recovery of cardiomyocyte apoptosis induced by tumor necrosis factor alpha (TNF-alpha) based on recording the change in cardiomyocyte adhesion to extracellular matrix (ECM). Electrochemical impedance spectroscopy (EIS) was employed in impedance to process the impedance spectra, followed by manual calibration with electrical cell-substrate impedance sensing (ECIS) technique. Adhesion profile of cardiomyocytes undergoing cell death process was recorded in a time course of equivalent cell-substrate distance. Multiple concentration levels of TNF-alpha (from 10 to 80 ng/mL) were applied to the cultured cardiomyocytes and the concentration-related adhesion profiles were recorded for the cell death process. An optimal concentration of TNF-alpha (20 ng/mL) was determined to induce cardiomyocyte apoptosis rather than necrosis because of its mild slope of developing cell detachment in 24-hour real-time monitoring. It was also observed in the Trypan blue exclusion (TBE) results that a gradual and significant increment in cell death rate was achieved with a concentration level of 20 ng/mL. Treat with optimal concentration of TNF-alpha, the cardiomyocytes first experienced a transient drop in cell-substrate distance followed a sustained cell detachment. The equivalent cell-substrate distance increased from 59.1 to 89.2 nm within 24 hours. The early change of cell adhesion was proven related to cardiomyocyte apoptosis with the following TUNEL test in which the treated cardiomyocytes suffered an apoptotic percentage of 21.1 ± 5.5 % (vs. 5.9 ± 2.5 % in the control sample). The early detection of cardiomyocyte apoptosis enabled flexible regulation of the process. It was demonstrated in our experiment that cardiomyocytes could recover from the TNF-alpha-induced apoptosis through the removal of TNF-alpha out of the cell culture before cell detachment. This novel assay has the potential to become a valuable high-throughput experimental approach in studying in vitro cardiomyocyte apoptosis research.
9:00 PM - FF6.5
Noble Metal Nanoparticle Aggregates as a Platform for SERS-Based Flow Cytometry.
Leif Brown 1 , Dakota Watson 2 , John Nolan 2 , Stephen Doorn 1
1 Chemistry Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States, 2 , La Jolla Bioengineering Institute, La Jolla, California, United States
Show Abstract9:00 PM - FF6.6
Bioresorbable Nanoparticles Enveloped by lipid ``Shells," ``Onions," or ``Flowers" as Synthetic Pathogens For Vaccine Design.
Anna Bershteyn 1 , Jose Chaparro 3 , Richard Yau 1 , Darrell Irvine 1 2
1 Materials Science and Engineering, MIT, Cambridge, Massachusetts, United States, 3 Chemistry, MIT, Cambridge, Massachusetts, United States, 2 Biological Engineering, MIT, Cambridge, Massachusetts, United States
Show Abstract9:00 PM - FF6.7
Silane Encapsulation of CdSe/ZnS Quantum Dots for Bio-imaging Applications.
Kwan-Yeul Paek 1 , Tae-Ho Yoon 1
1 Materials Science and Engineering, GIST, Gwangju Korea (the Republic of)
Show AbstractCdSe/ZnS quantum dots(QDs) were prepared and modified by silane encapsulation for bio-imaging applications. First, CdSe/ZnS QDs were prepared via colloidal method and stabilized with TOPO coating. Next, the QDs were encapsulated with silane coupling agents via hydrophobic interactions and quantum yield of the modified QDs was optimized as a function of the hydrocarbon length of silane coupling agents; n-octyltriethoxysilane(n=8), dodecyltriethoxysilane(n=12) and hexadecyltriethoxysilane(n=16). Finally, the silane encapsulated QDs were subjected to coating of 3-aminopropyltrimethoxysilane to form cross-linked layer of silanol groups and amino functional groups on the outer layer, which can be further reacted with bio-molecules. The silane encapsulated QDs were characterized by UV-vis, PL and TEM, and water-solubility, biocompatibility and cytotoxicity were evaluated by single cell imaging in vitro and in vivo.
9:00 PM - FF6.8
Targeted Nuclear Delivery by Peptide Coated Quantum Dots.
ChiungWen Kuo 1 , Peilin Chen 1
1 Research Center for Applied Sciences, Academia Sinica, Taipei Taiwan
Show Abstract9:00 PM - FF6.9
Miniaturized, Implantable Biosensor for Glucose Monitoring.
Fotios Papadimitrakopoulos 1 2 , Diane Burgess 3 , Faquir Jain 4 , Santhisagar Vaddiraju 1 , Upkar Bharadwaj 3 , Yan Wang 3
1 Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, Connecticut, United States, 2 Department of Chemistry, University of Connecticut, Storrs, Connecticut, United States, 3 Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, United States, 4 Electrical and Computer Engineering, University of Connecticut, Storrs, Connecticut, United States
Show Abstract
Symposium Organizers
Larry Nagahara National Cancer Institute
Thomas Thundat Oak Ridge National Laboratory
Sangeeta Bhatia Massachusetts Institute of Technology
Anja Boisen Technical University of Denmark
Kazunori Kataoka The University of Tokyo
FF7: Multifunctional Nanoparticles for Biomedical Applications
Session Chairs
Wednesday AM, December 03, 2008
Room 304 (Hynes)
9:00 AM - FF7.1
Cytotoxicity and Cell Uptake of Biofunctionalized Lanthanide Doped Hydrophically Ligated NaYF4 Upconversion Nanophosphors.
Jianbo Chen 1 , Jingning Shan 1 , Emily Paetzell 1 , Winston Soboyejo 1 , Yiguang Ju 1
1 Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey, United States
Show AbstractThis paper presents the results of an experimental study of cytotoxicity and cell uptake of lanthanide ion doped hexagonal phase NaYF4:Yb,Er upconversion nanophosphors (UCNPs) with controlled average sizes of 10 nm, 50 nm and 100 nm. Surface biofunctionalization of the hydrophobic UCNPs was achieved by introducing amino and carboxyl groups, respectively. Amino groups were conjugated to a thin coating layer of SiO2 using the APS (3-aminopropyltrimethoxy silane) reaction. The carboxyl groups on surface were added directly by coating with a modified amphiphilic polyacrylic acids (PAA) polymer. Cell uptake was accomplished by incubating the UCNPs with human osteosarcoma (HOS) cells and breast cancer cells. The different stages of endocytosis were then elucidated using transmission electron microscopy (TEM). MTT assays were then used to study the particle size dependence of the cytotoxicity of the functionalized UCNPs in HOS cells and human breast cancer cells (MDA-MB-231). The implications of the results are discussed for potential applications of UCNPs in biomedical imaging and photodynamic therapy.Keywords: upconversion nanophosphors, biofunctionalization, cytotoxicity, size effects, endocytosis, biomedical imaging and photodynamic therapy
9:15 AM - FF7.2
Multifunctional Nanostructured Materials based on Uniform Nanoparticles for Simultaneous Biomedical Imaging and Drug Delivery.
Taeghwan Hyeon 1 , Jaeyun Kim 1 , Yuanzhe Piao 1 , Nohyun Lee 1 , Ji Eun Lee 1 , Taeho Kim 1
1 School of Chemical and Biological Engineering, Seoul National University, Seoul Korea (the Republic of)
Show AbstractAbstract. Clever combination of different nanoscale materials will lead to the development of multifunctional nano-biomedical platforms for simultaneous targeted delivery, fast diagnosis, and efficient therapy. In this presentation, I would like to present some of our group’s recent results on the designed fabrication of multifunctional nanostructured materials based on uniform-sized nanoparticles and their bio-medical applications. We fabricated uniform-sized core/shell nanoparticles composed of monodisperse superparamagnetic nanocrystal core and uniform mesoporous silica shell. Fluorescent dyes can be easily anchored into the silica walls of the core/shell nanoparticles, and the functionalization with PEG increased colloidal stability of the nanoparticles significantly in phosphate buffered solution. The accumulation of the core/shell nanoparticles in the tumor sites were successfully detected by in vivo MR and fluorescent imaging, demonstrating the multimodal imaging capability. The anticancer drug loaded core/shell nanoparticles were successfully delivered to cancer cells. We fabricated hollow magnetite nanocapsules through a novel wrap-bake-peel process. The synthesized water-dispersible magnetite nanocapsules were successfully employed not only as a drug delivery vehicle, but also as a T2 MRI contrast agent. We designed and fabricated multifunctional polymer nanomedical platforms composed of inorganic nanocrystals of Fe3O4 or CdSe/ZnS, doxorubicin embedded in biodegradable PLGA polymer nanoparticles conjugated with cancer targeting pegylated folate. Cancer-targeted, MRI imaging and optical imaging, as well as drug delivery, were successfully demonstrated by the multifunctional polymer nanoparticles. In addition, Fe3O4 nanoparticles loaded in the polymer nanoparticles facilitated the magnetic guiding of the polymer particles, thereby increasing the synergetic targeting efficiency.
9:30 AM - **FF7.3
Multifunctional Nanosystems for Cancer-Targeted Imaging and Drug Delivery.
Mansoor Amiji 1
1 Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States
Show AbstractWith rapid advances in molecular biology and genetic engineering, there is an unprecedented opportunity for early disease diagnosis and targeted delivery of molecular medicines to specific tissues and cells. Nanotechnology is expected to have a revolutionary impact on medicine and especially in prevention, diagnosis, and treatment of cancer. In this presentation, I will provide an overview of the different nanotechnology platforms that we have developed for targeted drug and gene delivery for treatment of cancer. Special emphasis will be placed on nano-platforms that offer opportunities for multi-functionalization to allow for stimuli-responsive release, simultaneous strategic delivery of multiple therapeutic agents, and combining imaging and therapeutic modalities. Results from our laboratory show that biodegradable and biocompatible nanosystems can provide versatile platforms for delivery of multiple therapeutic agents and image contrast agents, specifically to enhance therapeutic effect and overcome drug resistance in cancer. In addition, nanoparticle systems can be engineered for tumor-targeted gene therapy and overcome biological barriers. In each case, special emphasis is placed on the use of safe materials for allow for rapid translation of these experimental technologies into clinical therapies that can benefit patients.
10:00 AM - **FF7.4
Hybrid Nanoparticles for Cancer Imaging and Therapy.
Wenbin Lin 1
1 , Univ of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Show AbstractIn this talk, I will present our latest work on designing magnetic resonance imaging contrast agents based on three different nanoparticle platforms--iron oxide nanoparticle clusters, nanoscale metal-organic frameworks, and mesoporous silica nanoparticles containing organic fluorophores and MR-enhancing Gd chelates. I will discuss the applications of these hybrid nanomaterials in in vitro and in vivo cancer imaging. For example, we have synthesized 75 nm mesoporous silica nanoparticles (MSNs) containing a hexagonal array of one-dimensional channels with diameters of 2.4 nm which were coated with a Si-DTTA-Gd complex. These MSN-Gd nanoparticles were characterized using SEM, TEM, TGA, BET, PXRD, and DCP; and the relaxivities were determined on both a 3.0 T and a 9.4 T MR scanner. The MSN-Gd particles exhibit very high MR relaxivity on a per Gd basis and even more impressive MR relaxivity on a per nanoparticle basis, owing to the ready access of water molecules through the nanochannels of the MSN-Gd particles and a high payload of Gd centers. The in vivo efficacy of these particles as MR contrast agents were further demonstrated with monocyte cells and mouse models. Both T1-weighted and T2-weighted signal enhancement can be obtained at doses much lower than what is currently being used. In vitro MTS assay and in vivo mouse studies indicated no acute toxicity of the MSN-Gd nanoparticles. Additionally, I will present our latest work on designing platinum-containing nanomaterials for cancer therapy.
10:30 AM - FF7.5
In vivo Biomedical Applications of Carbon Nanotubes.
Zhuang Liu 1 , Kevin Welsher 1 , Kai Chen 2 , Xiaoyuan Chen 2 , Hongjie Dai 1
1 Chemistry, Stanford University, Stanford, California, United States, 2 Radiology, Stanford University, Stanford, California, United States
Show AbstractBiological applications of carbon nanotubes have been attracting a lot of attentions recently. In the past few years, we have studied the in vivo biodistribution, tumor targeting, long term fate and toxicity of functionalized single walled carbon nanotubes (SWNTs). We have uncovered that SWNTs with proper surface chemistry are biocompatible and non-toxic in vitro to cells. After intravenously administrated into mice, SWNTs are accumulated in the reticuloendothelial systems (RES) including liver and spleen, and slowly excreted via biliary pathway in feces without exhibiting obvious side effect. Efficient tumor targeting can be achieved by conjugating SWNTs with a targeting peptide. Our results suggest that surface functionalization is the key for the in vivo behaviors of carbon nanotubes. Prolonged blood circulation, improved tumor targeting, reduced RES uptake and accelerated excretion of SWNTs can be realized by optimizing their surface coating. As a pilot effort towards in vivo cancer therapy, we have conjugated paclitaxel (PTX), a widely used cancer chemotherapy drug to branched polyethylene-glycol (PEG) chains on SWNTs via a cleavable ester bond to obtain a water soluble SWNT-paclitaxel conjugate (SWNT-PTX). SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol® formulated by cremophor in a murine 4T1 breast-cancer model without obvious side effects. For the first time we have shown that carbon nanotubes can be used as drug delivery vehicles to achieve in vivo cancer treatment efficacy in mice. Moreover, the intrinsic optical properties of SWNTs allow us to track and image them in vitro and in vivo. Carbon nanotubes are promising materials for future multimodality cancer therapy and imaging.
10:45 AM - FF7.6
Multi-functional Magnetic Nanoplatforms for Targeted Delivery, MRI Contrast Enhancement and Magnetic Hyperthermia.
Dattatri Nagesha 1 , Evin Gultepe 1 , Rishikesh Sawant 2 , Vladimir Torchilin 2 , Aditi Jhaveri 2 , Robert Campbell 2 , Lucy Song 3 , Nikos Soukos 3 , Srinivas Sridhar 1
1 Physics, Northeastern University, Boston, Massachusetts, United States, 2 Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States, 3 , Forsyth Dental Institute, Boston, Massachusetts, United States
Show AbstractWe describe the development and use of multi-functional magnetic nanoplatforms for diagnostics, imaging and therapeutic applications. Using polymeric magnetomicelles (polyethylene glycol/phosphatidylethanolamine) and cationic liposomes encapsulated with superparamagnetic iron oxide nanoparticles, they were studied for use in diagnosis as a contrast enhancing agent in magnetic resonance imaging (MRI), in therapy for field-directed tumor delivery and as an energy delivery agent in magnetic hyperthermia. These magnetic nanoplatforms were characterized for their size, surface charge and magnetic properties. For use as contrast agent, the T2 relaxation of these magnetomicelles in human breast carcinoma MCF-7 cells was measured using Nuclear Magnetic Resonance (NMR) spectrometer. The hyperthermia effect of iron oxide nanoparticles on bacteria was studied by applying alternating magnetic field on e. faecalis and e.gingivalis incubated with these nanoparticles. Results from these in vitro studies will be presented.This work was supported by NSF grant DGE-0504331, the NIH grants R01EB01961 and RO1 EN002995, and by Northeastern University.
11:30 AM - **FF7.7
In Vivo Targeting of Hollow Gold Nanospheres for Selective Phototherma Ablation of Solid Tumors.
Chun Li 1
1 , UT M. D. Anderson Cancer Center, Houston, Texas, United States
Show AbstractLaser-induced photothermal ablation therapy (PTA) is a promising technique for cancer treatment. Efficient PTA can be mediated with gold nanoshells conjugated with homing moieties which preferentially accumulates into the neoplastic tissue. Here, we will describe a new class of molecular specific photothermal coupling agents based on hollow gold nanospheres (HAuNS, average diameter ~30 nm) covalently attached to monoclonal antibody and peptide ligands directed at tumor-surface receptors. We will present data on the synthesis, characterization, and efficient in vivo delivery of targeted HAuNS, as well as treatment response with PTA therapy after systemic administration of targeting HAuNS into nude mice bearing human tumors. We will also discuss important factors that can influence the efficiency of active targeting with gold nanoparticles. Finally, we will present data towards MRI-visible gold nanoshells and photoacoustic imaging with HAuNS that allow combined detection and therapy of cancer.
12:00 PM - FF7.8
In vivo Monitoring of Gold Nanorods and Tissue Damage Mediated with Their Photothermal Effect.
Takuro Niidome 1 2 3 , Yasuyuki Akiyama 1 , Kohei Shimoda 1 , Takahito Kawano 1 , Takeshi Mori 1 2 , Yoshiki Katayama 1 2 , Yasuro Niidome 1
1 Department of Applied Chemistry, Kyushu University, Fukuoka, Fukuoka, Japan, 2 Center for Future Chemistry, Kyushu University, Fukuoka, Fukuoka, Japan, 3 PRESTO, JST, Kawaguchi, Saitama, Japan
Show AbstractGold nanorods, rod-shaped gold nanoparticles, show two surface plasmon bands corresponding to the transverse and longitudinal surface plasmon bands in the visible (~ 520 nm) and the near infrared regions (~ 900 nm), respectively. The near-infrared region is ideally suited for in vivo imaging and therapy due to minimum light absorption of intrinsic chromophores, hemoglobin (< 650 nm), and water (> 900 nm), indicating maximal penetration of light into tissues. In addition, since the adsorbed light energy is converted to heat, the nanorods are expected to use as a nanodevice for photothermal therapy. Recently, we succeeded to prepare biocompatible gold nanorods by coating PEG chain. Long lasting circulation of the gold nanorods was observed after intravenously injection (T. Niidome et al., J. Control. Release, 114, 343-347, 2006).
Firstly, we tried to use the gold nanorods as a probe for near infrared light bioimaging. After intravenous injection of the gold nanorods into mice, absorbance spectra of the mice abdomen were directly monitored using a spectrophotometer equipped with an integrating sphere. The absorbance at 900 nm from the gold nanorods immediately increased after injection, and reached a plateau. The injection of phosphatidylcholine-modified gold nanorods also increase the absorbance at 900 nm, but the absorbance decreased single-exponentially with 1.3 min of half-life. In vivo spectral changes of gold nanorods depended on the surface characters could be observed in real time by using simple spectroscopic measurements.
Next, to demonstrate photothermal tissue damage achieved by the photothermal effect of the gold nanorods, the PEG-modified gold nanorods were injected into the muscle in the hind limbs of mice, then the muscle was irradiated with near infrared pulsed laser light. Significant tissue damage was observed only in the case of both gold nanorods injection and laser irradiation. We injected the gold nanorods directly into subcutaneous tumors in mice, and then irradiated the tumor with near infrared pulsed laser light. Significant suppression of tumor growth was observed. In the case of the intravenous injection of gold nanorods, the suppression of tumor growth was weaker than for the case of direct injection, indicating that the targeted delivery of gold nanorods to the tumor tissue is an important key to improve the therapeutic effect.
12:15 PM - FF7.9
Quantification of the Photothermal Effect of Immuno Gold Nanocages for Targeted Cancer Therapy.
Leslie Au 1 , Desheng Zheng 2 , Fei Zhou 3 , Zhi-Yuan Li 3 , Xingde Li 2 , Younan Xia 1
1 Biomedical Engineering, Washington University, St. Louis, Missouri, United States, 2 Bioengineering, University of Washington, Seattle, Washington, United States, 3 Institute of Physics, Chinese Academy of Sciences, Beijing China
Show Abstract12:30 PM - FF7.10
Heat-induced in Vivo Tumor Destruction by Photothermal Effect of Carbon Nanotubes.
Hye Kyung Moon 1 , Hee Cheul Choi 1
1 Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang Korea (the Republic of)
Show AbstractNovel and effective approaches to treat cancer disease with minimal side effects are desperately needed. Nanotherapeutics combined with oncology is recently attracted to offer great opportunities for developing diagnostics and therapies of cancer disease. Especially, photothermal therapy via near infrared heating with nanoscale materials is an emerging field of nanotherapeutics. Such optothermally active nanomaterials can destruct tumor cells in a non-invasive manner by converting absorbed near infrared light (NIR) into thermal heat via nonradiative mechanism. Much attention has been focused on development of photothermal agent with large absorption cross-section of near-infrared light (NIR), producing hyperthermia. Carbon nanotube is an uprising candidate to serve as a potent photothermal therapeutic agent. It has a strong optical absorption property in near-infrared region (NIR), highly favorable intrinsic chemical and optical properties for biomedical application. We demonstrate that solid tumors in nude mouse are completely eradicated by photothemal effect of carbon nanotubes in near-infrared field (NIR). For application of photothermal therapy, we synthesize biocompatible carbon nanotube suspension by pegylation with minimal toxicity. And we locally inject the pegylated carbon nanotubes and irradiate near-infrared light (NIR) with 3W/cm2 to the tumor region. From only carbon nanotube injected mouse, tumor cells are completely destroyed by irradiation of near-infrared light (NIR) comparing with phosphate buffer saline (PBS) treated case. Continuous near-infrared light (NIR) radiation can cause thermo-necrosis because of excessive local heating of carbon nanotube injected site. It is proved that heat generated from carbon nanotubes can cause cell death by immunohistochemistry. The photothermal treated mouse is quite healthy with no toxicity by continuously monitoring over six months. These results suggest that carbon nanotubes may potentially serve as an effective photothermal therapeutic agent and provide great potential for clinical practice for cancer treatment.
12:45 PM - FF7.11
Thermal Destruction of Cancer using Radiofrequency Heating of Carbon Nanotubes, Gold Nanoparticles and Nanoshells.
Paul Cherukuri 1 2 3 , Christine Moran 1 3 , Sean Wainerdi 1 , Benjamin Wiley 2 , Katrina Briggs 1 , Christopher Gannon 1 , Steven Curley 1 2
1 , The University of Texas MD Anderson Cancer Center, Houston, Texas, United States, 2 , Harvard University, Boston, Massachusetts, United States, 3 , Rice University, Houston, Texas, United States
Show AbstractWe show that aqueous suspensions of metallic nanoparticles absorb shortwave radiofrequency energy (13.56 MHz) and produce heat (> 70 °C) that destroys cancer cells. The thermal efficiency (~ 75,000-300,000 W/g) associated with RF heating of metallic nanoparticles far exceeds methods that utilize optical energy or alternating magnetic fields. Gold nanoparticles and/or carbon nanotubes internalized within 3 different human cancer cell types were exposed to 2 min of RF energy, and the heat produced killed all cancer cells within 48 hrs. Furthermore, carbon nanotubes injected directly into deep tissue liver tumors within rabbits and exposed to RF fields, heated rapidly and destroyed tumors without collateral damage to other organs or structures within the animals. Given the whole body depth penetration of RF energy and the remarkable thermal properties of nanoparticles under radiowaves, RF heating of nanoparticles demonstrates its potential for treating deep tissue tumors without surgical intervention or toxic chemicals.
FF8: Interfacial Surface Functionalizaation and Dynamics for Biomedical Applications
Session Chairs
Wednesday PM, December 03, 2008
Room 304 (Hynes)
2:30 PM - **FF8.1
Zwitterionic Materials and Coatings for Biomedical Applications.
Shaoyi Jiang 1
1 Chemical Engineering, University of Washington, Seattle, Washington, United States
Show AbstractProtein-resistant materials and coatings are highly desirable for many biomedical applications ranging from diagnostics to medical implants. Poly(ethylene glycol) (PEG) has been widely used as protein-resistant materials. However, the susceptibility of PEG to oxidation damage has limited its applications. In this work, the design, synthesis and biomedical applications of ultra low fouling zwitterionic materials, particularly sulfobetiane (SB) and carboxybetaine (CB), will be presented. These zwitterionic materials and coatings are shown to be highly resistant to nonspecific protein adsorption even from undiluted blood plasma and serum and to bacterial adhesion/biofilm formation from both Gram positive and negative bacteria. Several methods have been used to attach zwitterionic groups onto a variety of surfaces, including atom transfer radical polymerization, self-assemby, interpenetrating polymer network, DOPA-assisted assembly, layer-by-layer growth, and copolymer physical adsorption. The key parameters such as film thicknesses and packing densities, which have significant influence on protein adsorption will be discussed. Furthermore, CB-based materials have several additional unique properties important for biomedical applications. CB-based materials are dual functional – not only they are highly resistant to protein adsorption, but also they have an abundance of functional groups for the convenient and efficient immobilization of proteins via simple NSH/EDC chemistry. Unreacted activated groups can be converted back to ultra low fouling zwitterionic groups upon hydrolysis. Thus, surface activation, protein immobilization, and surface de-activation can be all performed on one CB material, enabling the development of very low background noise protein arrays for nanosensors and of highly stable nanoparticles for targeted diagnostics/delivery in complex media. CB-based materials are also responsive to environmental (ionic strength and pH) and structural (the spacer group between two charged groups) changes, enabling the controlled release of drugs and the recovery of microorganisms. In addition, molecular-level nonfouling mechanisms will also be presented for PEG, zwitterionic, and sugar groups using a combined experimental and molecular simulation approach. Molecular principles learned are being applied to the design of other ultra low fouling zwitterionic and mixed charge materials.
3:00 PM - FF8.2
Nanoparticles for Targeted PET Imaging.
Eric Pressly 1 , Aviv Hagooly 2 , Monica Shokeen 2 , Carolyn Anderson 2 , Michael Welch 2 , Craig Hawker 1
1 Materials, Materials Research Lab, Santa Barbara, California, United States, 2 Radiology, washington University, St. Louis, Missouri, United States
Show AbstractWe have recently developed a novel methodology for the quantitative attachment of targeting peptides to our long circulating self-assembled polymer nanoparticles. This approach provides a basis for understanding the loading effects of targeting groups on a nanoparticle's surface. Herein, we study the effects of varying peptide loadings on the nanoparticle’s surface by in vitro cell and plate assays and standard biodistribution techniques in order to optimize our nanoparticles for targeted PET imaging. Results of targeting in heart disease animal models will be discussed as well as recent results involving incorporation of therapeutics.
3:15 PM - FF8.3
Nanoscale ``Curtain Rods": High-Throughput Tools for Studying DNA-Protein Interactions.
Teresa Fazio 1 , Mari-Liis Visnapuu 2 , Eric Greene 2 , Shalom Wind 1
1 Applied Physics and Applied Mathematics, Columbia University, New York, New York, United States, 2 Biochemistry and Molecular Biophysics, Columbia University, New York, New York, United States
Show Abstract3:30 PM - FF8.4
Cell Membrane Penetration by Amphiphilic 'rippled' Nanoparticles.
Ayush Verma 1 , Oktay Uzun 1 , Ying Hu 1 , Darrell Irvine 1 , Francesco Stellacci 1
1 , MIT, Cambridge, Massachusetts, United States
Show AbstractThe interaction of nanomaterials with cell membranes is key tonumerous applications such as drug/gene delivery, phototherapy and imaging.Typically, nanomaterials are internalized into cells via endocytosis and areunable to escape endosomes or penetrate the cell membrane to reach the cellmachinery located in the cytosol. Among synthetic materials, cationicnanoparticles (with some hydrophobic content) have shown the ability topermeate cell membrane by creating pores, although this process leads tocytotoxicity.Here we display that synthetic nanoparticles coated with ordered subnanometeramphiphilic striations of anionic and hydrophobic groups readily permeate cellmembranes without any signs of cytotoxicity. Interestingly, nanoparticlescomposed of the same groups, but in a random organization, display aninabilityto penetrate the cell membranes. This work illustrates the importance ofligand/functional group organization on the cell membrane penetrating abilityof nanomaterials and may also lead to efficient low-toxicity drug-deliverysystems based on the design rules for membrane penetration identified here.
4:15 PM - FF8.5
Controlling the Nanoparticle-Biological Interface.
Kimberly Hamad-Schifferli 1
1 Biological Engineering and Mechanical Engineering, MIT, Cambridge, Massachusetts, United States
Show AbstractBecause biomolecules are inherently on the nanoscale, nanotechnology has emerged as an appropriate means for interfacing to biology. In order to fully realize the potential of nanomedicine, this requires both understanding the inorganic properties of the nanoparticle as well as creating an interface that is compatible with the complex and highly disordered environments of real biological systems. We will discuss the use of nanoparticles composed of Au, Fe3O4, Fe2O3, CoFe2O4, and similar materials in biological applications by engineering both the inorganic properties of the nanoparticles along with creating optimal biological interfaces. We study the interface between the nanoparticle and covalently linked proteins. Labeling proteins with nanoparticles has been utilized for many applications but often the structure of the protein in the conjugate is not characterized. In addition, site-specific labeling of the protein with a nanoparticle has been achieved for only a limited set of proteins and nanoparticles. We present work in which we study the interface between nanoparticles and the protein cytochrome c. We vary nanoparticle ligand and composition, as well as labeling site on the protein. Biophysical techniques such as quantitative gel electrophoresis, circular dichroism, and optical spectroscopy are used to characterize the structure of the protein in the conjugate. These experiments allow us to understand some of the chemical interactions involved in non-specific adsorption, and come up with general design rules for optimal conjugation.
4:30 PM - FF8.6
Low-Biofouling Click Multilayers for Promoting Cell Adhesion and Growth.
Georgina Such 1 , Cameron Kinnane 1 , Kim Wark 2 , Angus Johnston 1
1 Chemical and Biomolecular Engineering, University of Melbourne, Parkville, Victoria, Australia, 2 Molecular and Health Technologies, CSIRO, Parkville, Victoria, Australia
Show AbstractThe design of functional materials with finely controlled and intelligent properties is extremely important for the generation of new biomedical approaches in areas such as delivery or implants technology. Click chemistry has generated significant interest in recent years as a tool to design such materials; it refers to covalent reactions, which are highly efficient under mild conditions. The most well documented example is the CuI catalyzed variant of the Huisgen 1,3 dipolar cycloaddition of azides and alkynes to form 1,2,3 triazoles. The reaction has many significant advantages such as it is simple, efficient and inert to a range of functionality present in the system. Recently, we combined click chemistry with an inexpensive and simple assembly technique, known as layer-by-layer (LbL) assembly to synthesize a variety of layered, stable ultrathin films and capsules from a single polymer type modified with the respective azide or alkyne moieties. The LbL technology is based on the serial adsorption of species with complementary interactions and has been widely used to prepare a diverse range of nano-engineered materials. As the click-LbL technology provides a generalizable, modular approach to design materials with various combinations of polymers and functionalizing molecules for sophisticated and multifunctional response, we sought to exploit this approach for the preparation of thin films with relevance to biomedical applications, where stable, low-fouling materials are required for the unwanted adhesion of proteins and cells. In this work we have prepared low-fouling poly(ethylene glycol) acrylate (PEG) multilayers through the click-LbL technique. These PEG surfaces demonstrated minimal cell binding. The films were then rendered cell-responsive by post-functionalization through the reaction of the excess click groups with a variant of the tripeptide sequence arginine-glycine-aspartate (RGD) to promote specific cell adhesion and growth. The ability to design precisely engineered low-fouling materials which can be easily postfunctionalized for intelligent response to their environment offers new opportunities for designing advanced materials for a range of therapeutic or diagnostic applications.
4:45 PM - FF8.7
The Control of Cell Adhesion and Viability by Zinc Oxide Nanorods.
Jiyeon Lee 1 , Byung Hwan Chu 1 , Fan Ren 1 , Benjamin Keselowsky 2 , Tanmay Lele 1
1 Chemical Engineering, University of Florida, Gainesville, Florida, United States, 2 Biomedical Engineering, University of Florida, Gainesville, Florida, United States
Show AbstractThe control of cell behavior on implanted biomaterials is needed for the success of implanted devices such as biosensors or drug delivery devices. In this study, we investigated the use of zinc oxide (ZnO) nanorods for modulating the adhesion and viability of NIH 3T3 fibroblasts, umbilical vein endothelial cells, and capillary endothelial cells. The cells on ZnO nanorods were rounded and not viable compared to the flat ZnO substrate. Scanning electron microscopy indicated that cells were not able to assemble lamellipodia on nanorods. Time-lapse phase contrast imaging showed that cells initially adherent to nanorods are unable to spread. Cells on nanorods were unable to assemble focal adhesions and stress fibers. We conclude that ZnO nanorods are potentially useful biomaterials to minimize cell adhesion and survival.
5:00 PM - FF8.8
Dynamic Surface to Control Cancer Cell Migration.
Ronald Lerum 1 , Harry Bermudez 1
1 Polymer Science and Engineering, Univeristy of Massachusetts, Amherst, Amherst, Massachusetts, United States
Show AbstractThe development of new biomaterials for probing cell-surface interactions is important to enhancing our understanding of cell adhesion and migration. Receptor-ligand interactions in cellular adhesion are extremely intricate and not entirely understood, however cells are known to respond to multiple environmental cues, which can be both biochemical and biophysical in nature. This form of communication has been linked to a number of cellular processes such as attachment, migration, morphology, invasion and/or cell death, which are especially relevant in cancer metastasis. Typically, cells that lose contact with their environment suffer from “anoikis” which is essentially cell death due to “homelessness”. Interestingly, invasive cancer cells are able to evade this demise and are able to migrate into and colonize foreign tissues. In this report, we intend to study the influence of dynamic surfaces on adhesion-receptor ligand interactions by developing biocompatible and bioactivated model surfaces. Cell surface adhesion and migration are primarily promoted by integrins, a class of transmembrane extracellular matrix proteins. Specific stimulation of these receptors can be obtained by using a cell adhesion ligand, arginine-glycine-aspartate (RGD), which is derived from fibronectin. This tripeptide RGD will be covalently immobilized onto an amphiphilic block copolymer such as polybutadiene-b-poly(ethylene glycol) PBd-b-PEG using tresylate chemistry. Biofunctionalization of this amphiphilic block copolymer will be mixed with unmodified material of similar and varied molecular weights which influence the overall lengths of the polymer as a means to control ligand concentration and accessibility. The hydrophobic block PBd provides a means for controlling surface diffusion either by cross-linking or physical entanglement as a result of increased molecular weight. The self-assembly and compression of the amphiphilic block copolymer at the air-water interface will enable us to transfer our polymer onto a substrate via a Langmuir-Blodgett (LB) technique to form a biomimetic bilayer. The isotherm at the air-water interface offers subjective control of the conformation and presentation of ligands on the surface as well as orientation (e.g. brush or mushroom) of the polymer. Once the LB technique is performed, the polymeric bilayer will closely resemble the physio-dynamic character of lipid membranes although have increased robustness and dynamic range. A discussion on the characterization of the surface by X-ray photoelectron spectroscopy, atomic force microscopy, fluorescence recovery after photobleaching, etc. will be presented. These surfaces will eventually be used to study the mechanism of invasive cancer cell adhesion and migration with a focus toward its anti-anoikis behavior. The tunability of our polymeric surface maybe used to advance our understanding of the metastatic ability of cancer cells (e.g. Hela cells) through receptor-ligand interactions.
5:15 PM - FF8.9
Nanoscale Bioarrays for the Study of Cytoskeletal Protein Binding Interactions.
Mark Schvartzman 1 5 , Julia Sable 3 5 , Justin Abramson 2 5 , Matteo Palma 2 5 , James Hone 2 5 , Sheetz Michael P. 3 5 , Shalom Wind 4 5
1 Chemical Engineering, Columbia University, New York, New York, United States, 5 Nanotechnology Center for Mechanics in Regenerative Medicine, Columbia University, New York, New York, United States, 3 Biological Sciences, Columbia University, New York, New York, United States, 2 Mechanical Engineering, Columbia University, New York, New York, United States, 4 Applied Physics, Columbia University, New York, New York, United States
Show AbstractContinued progress in solid-state nanofabrication technology enables the creation of structures in the size regime of biomolecules, i.e., ~ tens of nanometers and below. In this work we implement a system that mimics biological spatial order using nanofabricated structures which are used for the study of the dependence of binding of large cytoskeletal proteins on the spatial arrangement of ligands. Theoretical analysis suggests that proper ligand spacing can increase binding affinity by orders of magnitude. We fabricate hierarchical arrays of nanostructures in which geometric parameters, such as spacing and orientation, are systematically varied. The arrays contain metal dots 5 - 10 nm in diameter, functionalized with linker molecules that specifically interact with individual protein binding sites. These dots can be arranged individually, in pairs, or in more complex patterns based on the structure of the molecules under investigation. In our work we use nanoimprint lithography (NIL) for the fabrication of these nanoarrays. The NIL templates are fabricated from diamond-like carbon (DLC) films on silicon. The fabrication consists of thermal nanoimprint and further pattern transfer by Au/Pd deposition and lift-off, assisted by an e-beam evaporated Ti hard mask. A post-lift-off anneal provides further reduction of feature size from ~10 - 15 nm to ~5 - 10 nm and a high degree of uniformity. Fabricated arrays of AuPd nano-dots are functionalized with fibronectin RGD motifs through a biotin-avidin-biotin linkage, with the unpatterned areas passivated by a PEG monolayer. Biofunctionalization of the pattern with thiolated peptides and further attachment to the functionalized domains of fluorescently labeled ligands is monitored by Total Internal Reflectance Fluorescence (TIRF) Microscopy. Differences in the spreading and morphology of 3T3 fibroblast cells plated on the arrays as a function of nanoarray parameters shed light on the role of ligand spacing in the formation of focal adhesions. Similarly, the topography of the environment of stem cells , modified in-vitro using different types of substrates and their structural parameters, can affect their behavior. The application of our nanoarrays to the fundamental study of stem cells, in terms of their response to the geometric arrangement of ligands, will be discussed as well.In summary, this presentation will describe the fabrication of arrays of ultra-small metal features using NIL technology, functionalization and implementation of these arrays in the study of the fundamentals of cell behavior, representing a new example of the enormous impact of nanofabrication on the life sciences.
5:30 PM - FF8.10
Gold/PEO-like Nanopatterns: Fabrication, Characterization and Investigation of Their Effect on Enhancing Biomolecule Affinity Reactions.
Ilaria Mannelli 1 , Andrea Valsesia 1 , Patricia Lisboa 1 , Stéphane Mornet 2 , Marielle Anger-Leroy 3 , Pascal Colpo 1 , François Rossi 1
1 Institute for Health and Consumer Protection, EC Joint Research Centre, Ispra Italy, 2 Condensed Matter Chemistry Institute of Bordeaux, CNRS, Pessac France, 3 , GenOptics, Orsay France
Show AbstractIn recent years many techniques have been investigated for the fabrication of nanopatterned surfaces. Among them colloidal lithography combined with the plasma polymer deposition and/or the self-assembly has shown to be a flexible technology for producing large area nanostructured surfaces in a fast and cheap way. At the same time, many studies have been done on the behaviour of biomolecules interacting with surfaces and/or particles with nanometre dimensions. In fact, it is well known that the interactions of the recognition bioelement (i.e. protein, nucleic acid) with the transduction surface and the conformation changes that molecules undergo after the interaction are fundamental aspects in biosensor development. At the same time, it is less known how the recognition biomolecule interacts with transduction surfaces that have been previously functionalised with nanofeatures having dimensions comparable with those of the biomolecules; and how, after the interaction, the native biomolecule conformation changes.In our laboratory, we have optimized a procedure for fabricating nanopatterned surfaces at sub-500 nm scale in which bioadhesive gold nanoarea are embedded, with crystalline arrangement, in a bioresistant matrix (PEO-like polymer). The so fabricated surfaces have been characterised by AFM and electrochemical analysis and their interaction with H2N functionalised Au nanoparticles have been investigated. The AFM images show the close packed hexagonal crystalline arrangement of the nanopattern array and the localization of the H2N-Au nanoparticles in the bioadhesive areas. The detection performances of these surfaces employed as transduction platform for studying biomolecule interactions have been investigated by a Surface Plasmon Resonance Imaging (SPRi) system. Recognition biomolecules were immobilised on the nanopatterned surface and the recognition reaction was monitored in real time with the SPRi system. The investigated nanopatterned surfaces showed an enhancement of the affinity reaction efficiency with respect to the non structured surfaces, demonstrating their capability of improving the binding site accessibility of the immobilized biological probes. Moreover, the nanopatterned surfaces have been employed as platform for microarray system development. Preliminary promising results have been obtained, indicating that label-free bioarray based on nanopatterned surface can reach lower detection limit (100 ng/ml of target molecule).
5:45 PM - FF8.11
Sensitivity Enhancement of Surface Plasmon Resonance Imaging by Nanoarrayed Organothiols.
Patricia Lisboa 1 , Andrea Valsesia 1 , Ilaria Mannelli 1 , Pascal Colpo 1 , François Rossi 1
1 JRC, European Commission, Ispra, VA, Italy
Show AbstractThe implementation of sensor platforms providing high sensitivity of detection is a crucial step for the design of the new analytical device generation for biosensor developments. Designing platform with active/non-actives region at nanoscale has shown already a drastic increase of detection sensitivity 1,2. The use of organothiols to create nanopatterns has been already studied showing that this type of chemistry is indicated to produce chemical contrasts for bio-applications 3. In this work, the effect of organothiols-nanopattern in Surface Plasmon Resonance imaging (SPRi) detection was studied. The gold surface of the SPRi chip was divided in two areas, one modified with a chemical nano-contrast based in two different organothiols (thiolated polyethylene oxide (PEO) and Mercaptohexadecanoic acid (MHD)) and the other modified uniformly with MHD. The SPRi study was based on the detection of the immunoreaction between Human IgG and anti-Human IgG (Ab specific) by comparing the results obtained with nanostructured and uniform carboxylic surface. First Human IgG was immobilised on the chip and after the recognition of different concentrations of anti-Human IgG was realised. The achieved SPRi signal was higher in the case of the nanostructured areas for all the tested concentrations. Since the active surface with carboxylic functionalities presented only 3% of the total area, one would expect the detection signal to be 3% of the signal obtained for the uniform MHD surface. The fact that the signal from the nanostructures is higher than in the MHD surfaces in SPRi detection is related to an amplification of signal due to the 2D crystalline character of the structures. This type of arrangement presents the geometry of a photonic crystal leading to the interaction between the Surface plasmon polaritron modes and the regular modulation of the dielectric constant of the surface above the gold film modifying the plasmon effect and consequently increasing the measured reflectivity. These results indicate that SPRi detection performance can be improved by the rational functionalisation of the prism surface with 2D crystalline nanopatterns. Moreover adhesive – nonadhesive nanopatterns are recognized to be good platforms for the correct immobilization of the biomolecules on biosensing surfaces.
FF9: Poster Session: Nanofabrication and Methods for Biomedical Applications
Session Chairs
Sangeeta Bhatia
Anja Boisen
Larry Nagahara
Thomas Thundat
Thursday AM, December 04, 2008
Exhibition Hall D (Hynes)
9:00 PM - FF9.1
ALD HfO2 as a Gate Insulator for BioFET and Capacitive Nanowire Biomolecule Sensors.
Yi Wei Chen 1 , Makoto Koto 3 , Tetsuya Kaneko 1 , Kris Toivola 1 , Yasuhiro Oshima 2 , Paul McIntyre 1
1 Material Science and Engineering, Stanford University, Stanford, California, United States, 3 , Canon Inc., Tokyo Japan, 2 , Tokyo Electron Ltd., Tokyo Japan
Show AbstractSemiconductor nanowire biosensors have been shown to have the potential for high sensitivity, label-free biomolecule detection with real time response. To make the biosensors more reliable, the nanowires should be covered by an insulator layer that is stable in biological solutions. Moreover, the capacitance of the insulator layer must be as high as possible such that the electric field modulation from the bio-molecule binding event can be efficiently translated into a conductance change (majority carrier depletion or accumulation) inside the nanowires. To study the stability and efficiency of the insulator layers, we use the capacitance-voltage (C-V) method with an electrolyte solutions acting as a top electrode. Our results show that native SiO2 on Si, which has been used commonly as the insulator layer for silicon nanowire biosensors reported in the literature, exhibits unstable C-V characteristics in electrolyte solutions, possibly due to ion penetration. A thicker SiO2 layer can reduce this effect, at the cost of degrading the capacitance density which is required for high sensitivity.We have investigated high dielectric constant HfO2 thin film insulators as a replacement for SiO2. Because of its higher dielectric constant, deposited HfO2 insulator layers provide high capacitance density comparable to that of native SiO2, while at the same time achieving stable C-V characteristics with a larger physical thickness. The atomic layer deposition (ALD) of conformal HfO2 thin films on Ge NWs of 40 nm diameter is demonstrated. By integrating ALD with vertical epitaxial growth of nanowires on silicon substrates, we are able to fabricate a capacitive nanowire biosensor without the use of lithography or other microfabrication techniques to define the device area. The prospects for this easily fabricated nanowire biosensor will be discussed.
9:00 PM - FF9.10
Fabrication of DNA Nanowire by Controlling DNA Movement on Solid Surface by Optical Tweezers.
Sho Fujii 1 , Katsuaki Kobayashi 1 , Shoich Toyabe 2 , Tetsuaki Okamoto 2 , Eiro Muneyuki 2 , Masa-aki Haga 1
1 Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Bunkyo-ku, Tokyo, Japan, 2 Department of Physics, Faculty of Science and Engineering, Chuo University, Bunkyo-ku, Tokyo, Japan
Show Abstract Controlling the DNA assemblies is one of the most important targets of bio-inspired nanomaterials. The specific base pairing and site selective modification of DNA have been widely used as a DNA chip on solid surface for the DNA diagnosis. On the other hand, DNA acts as a template or a scaffold for the fabrication of functional nanoscale materials such as nanowire. Because of negatively charged backbone in DNA, the electrostatic modification with cationic nanoparticles and metallization lead to the functionalization of DNA nanowires, which has opened new dimension of bottom-up fabrication. Our study is focusing on positioning and controlling a nanoarray of DNA-based nanowires, which is a challenging task for the fabrication of nanodevices. Here, we have successfully achieved the DNA nanowiring between patterned gold electrodes with micrometer gap by controlling a DNA movement on solid surface using optical tweezers. A patterned Au electrode with micrometer-size gap was prepared by photolithography on quartz substrate and DNA capture molecules were immobilized on gold electrodes by using the orthogonal self-assembly. Lambda DNA was labeled with biotin at its 3’ end to attach a streptavidin-coated bead. This DNA-bead composite was stained by organic dye(SYBR Gold), which makes possible to observe the movement of DNA-modified beads by a fluorescence microscope. In a thin layer cell (thickness: ca. 40 μm), constructed from the gold patterned quartz substrate (upper side) and a cover glass (bottom side), the DNA attached beads was optically trapped by YAG laser (1064 nm) and relocated close to one of gold electrodes in order to fix the position. Then, a laser (1064 nm) was irradiated on other side of the gold electrode surface, which leads to the extension and wiring of the DNA between gold electrodes. The laser focusing irradiation only on gold surface makes possible to extend DNA helices. Therefore, the present method can be applied to fabricate a DNA-wired nanoarray on a particular position. We will also present the mechanism of DNA extension and its application toward bio-inspired nanotechnology.
9:00 PM - FF9.11
Capacitive Biosensor Based on a Micron-sized Nanoporous Structure.
Lia Moreno i Codinachs 1 , Christopher Birkenstock 1 , Tonko Garma 1 , Robert Zierold 2 , Julien Bachmann 2 , Kornelius Nielsch 2 , Michael J. Schoening 3 4 , Anna Fontcuberta i Morral 1 5
1 , Walter Schottky Institut-Tecnische Universitaet Muenchen, Garching Germany, 2 , Institute of Applied Physics, University of Hamburg, Hamburg Germany, 3 Laboratory for Chemical Sensors and Biosensors, Aachen University of Applied Sciences, Juelich Campus, Juelich Germany, 4 , Research Centre Jülich GmbH, Institute for Thin Films and Interfaces, Juelich Germany, 5 , École Polytechnique Fédérale De Lausanne, Institut des Matériaux, Lausanne Switzerland
Show AbstractTemperature and pH measurements have been performed using a capacitive sensors based on different Anodic Alumina Oxide (AAO) pore membranes. The aim of this work is to develop a biosensor in which the sensitive area is placed inside the pores.AAO pore structures have demonstrated to be advisable alternative nano sensors due to the high surface-to-volume ratio, high pore density, low cost synthesis and high stability at elevated temperatures and humidity levels. By means of Atomic Layer Deposition (ALD) tecnique, the alumina pores can be coated with several materials, basically oxides [1]. Hence, small diameter pores with different materials can be obtained giving the chance to functionalize the surface to get sensors sensitive to different biological or chemical species. Alumina pore structures have been used in the past as humidity sensors (RH -relative humidity- sensors) due to the ability of this material to absorb water vapor [2-4]. Nonetheless, the use of AAO as temperature, pH or biosensors has been to date not greater depth studied.The preliminary measurements have been performed in vertical oriented pores structures such as Al/Al2O3/Au and Si/SiO2/Al/Al2O3/Au due to its simplicity concerning on the fabrication processes.Here we present the first results we have obtained with a structure Al/Al2O3/Au as a temperature sensor in air (35% humidity) based on capacitive measurements. A linear C-T response in a wide range of temperatures has been obtained.Two sets of measurements of the capacitance at fixed frequency and potential with both structures have been performed, either varying the temperature in water or the pH, and linear responses have been also obtained.Another set of impedance measurements have been also done with the samples based on the structure Al/Al2O3/Au in which some of the Al2O3 pores have been coated with three different oxides (SiO2, ZrO2 and TiO2). In these measurements, a frequency sweep has been performed between 1kHz and 1 MHz, and the variation of the capacitance respect to the potential has been studied depending on the pH of the solution.Further measurements will be performed with an EIS (Electrolyte- Insulator- Semiconductor) structure (Au/Si/SiO2/Al2O3/Au), using impedance spectroscopy and studying the response of the samples regarding to the pH and the temperature of the solution. Once these sensors will be characterized, a biomolecular immobilization will be performed inside the pores to get the final biosensor device.REFERENCES(1)M. Knez et al.; Adv. Mater., 19 (2007) pp.3425.(2)O.K. Varghese et al.; J. of Mat. Res., 17 (2002) pp 1162.(3)R.K. Nahar; Sensors and Actuators B, 63 (2000) pp.49.(4)V. Timár-Horváth et al.; Proceedings DTIP of MEMS & MOEMS, (2007) Italy.
9:00 PM - FF9.12
Arrangement Control of Porous Alumina Micro-scaled Domes Self-organized in Anodic Oxidation.
Tsukamoto Takahiro 1 , Ogino Toshio 1
1 , Yokohama National University, Yokohama Japan
Show AbstractNanostructures are indispensable tools to handle biological molecules. Porous alumina prepared by anodic oxidation of an Al sheet is a unique material because it exhibits a self-organized ordered nano-hole array with a honeycomb arrangement. The diameter of nano-holes is controllable by adjusting the applied voltage, and their depth is several micrometers. In actual applications, such as integrated bio-devices, nano-pore arrays should be separated into micro-scaled domains because integration technique is more strongly required than discrete devices. We aim to fabricate isolated three-dimensional porous alumina structures. Previously, we reported that porous alumina micro-scaled architectures are formed during the anodic oxidation of an Al sheet [1]. These are dome-like shaped and vertically aligned pores are self-organized. Although these domes are buried in the porous alumina films, we can remove the outside of the domes by an etching. In this paper, we report the arrangement control of such porous alumina domes by scratch patterns on the Al sheets.An Al sheet was cleaned in acetone and soaked for a couple of second in 100 wt% phosphoric acid solution at 60°C. The treated substrates were then oxidized in air at 300°C. For arrangement control of the domes, the Al sheet was scratched. The Al substrates were anodized in an oxalic acid solution (0.3 M) at 40 volts for 1 hour. After the anodization, the outside of the domes was selectively etched using a 20 wt% phosphoric acid at 60°C. When a 8 wt% phosphoric acid was used, a uniform porous alumina film was obtained. The fabricated substrates were observed by an SEM.The porous alumina domes were observed on the whole area of the Al sheet surface after the etching. The bottom widths of the domes are from 1 to 5 μm and the height is approximately 5 μm. We confirmed that uniformly distributed vertical nano-pores formed inside the domes. We found that the domes were preferentially formed just above the scratch lines on the substrate. Therefore, we can artificially arrange porous alumina domes by the scratch. Since a high density of isolated three-dimensional structures with sub-100 nm pores can be fabricated by a simple process, these architectures are promising materials for fabrication of an integrated bio-sensors. [1] T. Tsukamoto, T. Oya, and T. Ogino, e-Journal of Surface Science and Nanotechnology, 6, pp. 147-151 (2008).
9:00 PM - FF9.13
Recognition and Adsorption of the Water-soluble X-ray Contrast Medium Iodixanol using Molecularly Imprinted Polymers for Biomedical Applications.
Zhan Liu 1 , David Bucknall 1 , Mark Allen 2
1 School of Polymer, Textile and Fiber Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States, 2 School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
Show AbstractThis work presents the first study on the recognition and adsorption of the water-soluble X-ray contrast medium iodixanol using synthetic molecularly imprinted polymers. Iodixanol has become a widely-used radiographic contrast agent administered by intravascular injection during imaging procedures and ultimately excreted by the kidneys. However, clinical studies show that renal clearance of iodixanol might lead to acute kidney injury, especially for at-risk patient populations. A nano-functional material that is able to molecularly recognize and selectively adsorb iodixanol could greatly ease the renal burden on these patients. Other biomedical applications of such iodixanol-imprinted polymers, including hemodialysis, diagnostic devices, and sensors, can also be envisaged.Iodixanol-imprinted polymers were prepared by the non-covalent imprinting technique in aqueous-based solvents using 4-vinylpyridine as the functional monomer and ethylene glycol dimethacrylate as the crosslinker. In this work, the present quantity of templates with respect to functional monomers, the crosslink density, and the porogenic solvent were extensively studied with the aid of a series of synthetic polymers to experimentally improve materials properties such as the binding capacity and imprint effect, and to investigate the imprinting mechanism. UV-Vis spectrometric analysis shows that the highest binding capacity that can be achieved from the optimized iodixanol-imprinted polymers is 284 mg/g dry polymer when examined in the aqueous solution with an initial concentration of 15 mg/ml. This is 7.8 times higher than the binding capacity of the control polymer and indicates a successful imprinting was achieved. SEM and BET surface analysis were also under taken to study the impact of surface morphology and porosity on the binding capacities of the polymers.This work has demonstrated the feasibility of non-covalently imprinting iodixanol and paves the way for iodixanol-imprinted polymers in biomedical applications. In addition to detailed mechanism elucidation, future work will include a selectivity study in aqueous solutions with competitive blood components, as well as demonstration of the adsorption utility of these polymers in plasma and blood in-vitro.
9:00 PM - FF9.14
Properties of Triazole Fungicide Particles Prepared by High Shear Process.
Ji Youn Yoo 1 , Myeong Jun Kim 2 , YoungChul Lee 2 , Jonghwi Lee 1
1 Department of Chemical Engineering and Materials Science, Chung-Ang University, Seoul Korea (the Republic of), 2 Green Engineering Team, Korea Institute of Industrial Technology, Cheonan-Si Korea (the Republic of)
Show AbstractINTRODUCTIONAntifungal azole compounds are structurally diverse and characterized by imidazole or triazole functionalities. This class includes drugs such as itraconazole, ketoconazole, fluconazole, and several others. Itraconazole is a triazole agent available for the treatment of histoplasmosis, blastomycosis, etc. Itraconazole is a weakly basic drug that was experimentally found to have very poor water-solubility. Itraconazole can only be ionized and solubilized in water at a very low pH. Increasing the surface area of active pharmaceutical ingredients by reducing particle size from microns to nanometers is an efficient way of improving the bioavailability of relatively insoluble drugs. The recent advance of particle size engineering in nanometer ranges has widened the formulation opportunities of relatively water-insoluble drugs. This study investigated the effect of particle size reduction and the physical properties of itraconazole particles prepared by high shear process. MATERIALS AND METHODSItraconazole particles were mixed with distilled water, and a polymeric stabilizer (hydroxypropyl methylcellulose). Then the mixtures were processed by a high shear extruder to break the microparticles to submicron particles. Characterizations after processing, such as particle size analysis, in vitro drug release tests and particle morphology observation were performed. RESULTSParticle Size Measurements and Morphology ObservationWhen itraconazole contents were over 50 wt%, the obtained mean particle sizes were between 600-800 nm. When the repeated number of high shear process increased, the mean particle sizes decreased. Itraconazole particle morphology observed by SEM was consistent to the results of particles size analysis. X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC) MeasurementsPossible changes in the crystallinity of itraconazole by the high shear process were checked by XRD and DSC. As the repeated number of high shear process increased, the degree of crystallinity of itraconazole was reduced.In Vitro Release StudyThe release rate of itraconazole from the particles prepared by high shear process was improved compared to that from the particles as received. More than 20 wt% itraconazole in nanoparticulate powders was released within 24 hrs. CONCLUSIONSItraconazole nanoparticles were successfully prepared in the size of 400 ~800 nm by the high shear process. Itraconazole particle morphology was consistent to the results of particles size analysis. As the repeated number of high shear process increased, the degree of crystallinity of itraconazole was reduced. More than 20 wt% itraconazole in particulate formulation prepared by the high shear process was released within 24 hrs.
9:00 PM - FF9.16
Fabrication of Artificial Cell Membranes Equipped with Carbon Nanotube Wires.
Toshinari Isono 1 , Hanako Tanaka 1 , Kenji Motomiya 1 , Toshio Ogino 1
1 Electrical and Computer Engineering, Yokohama National University, Yokohama Japan
Show AbstractRecently, neuronal and intercellular signal transfer systems attract much attention because they are basis of biomimetic devices, such as biosensors, molecular communication, neuronal computing and drug screening devices. The signal transfer systems in cell membranes are applicable to the drug screening because the membrane proteins are closely related to many diseases. An artificial cell membrane, consisting of a lipid bilayer and membrane proteins, is often used as a model system for fundamental studies. In these devices, the important thing is how to detect the biomolecular signals. The metallic electrodes are usually used for the biosignal detection. However, the metallic wires are larger than the protein dimension and the functional domain sizes on a cell membrane, and, therefore, a local signal cannot be obtained. In this paper, we propose carbon nanotube (CNT) wiring for the input and output of membrane protein signals. Because the CNTs are electrically conductive and their diameters are nanometer scaled, they are promising to sensitively detect a local response for a local stimulus to biomolecules. Generally, it is difficult to form lipid bilayers on a hydrophobic region though CNTs are hydrophobic. In this study, we have fabricated a device structure of the supported lipid bilayer equipped with the carbon nanotube wiring on a substrate.The CNTs were grown on SiO2/Si substrates by a chemical vapor deposition using methane gas as a carbon source. Ferritin, a protein containing an iron-core, was used as the catalyst for the CNT growth. Because a ferritin molecule contains a well-defined iron nanoparticle, almost uniform single walled CNTs can be grown. Next, supported phospholipid bilayers were formed by the vesicle fusion method on the substrate with the CNTs in a buffer solution. In this method, the vesicles adhere on the hydrophilic SiO2 surface and rupture, transforming into a planar bilayer. The lipid bilayers deposited on a surface with the CNTs were observed by an atomic force microscopy (AFM) at room temperature in a liquid environment.In the AFM images, we clearly observed the lipid bilayers over the pre-grown CNTs. The vesicles ruptured on a hydrophilic surface and covered the surface partially including the hydrophobic CNTs. The lipid bilayer may cover the hydrophobic regions when the dimension of the hydrophobic regions is negligible, such as the present case. Additionally, the lipid bilayer is supported onto a substrate surface through a water layer with a thickness about 1~2 nm. Since the grown CNT diameter is about 1 nm, the supported lipid bilayers can form on the substrate with the hydrophobic CNTs. By applying the present structure, consisting of CNT electrodes and lipid bilayers, to artificial cell membrane devices, a sensitive detection of local biosignals is expected.
9:00 PM - FF9.17
A Lab-on-a-Chip for Clinical Analysis with Acoustic Microagitation based on Piezoelectric Poly(Vinilidene Fluoride).
Senentxu Lanceros-Mendez 1 , P. Martins 1 , V. Cardoso 2 , J. Serrado-Nunes 1 , L. Rebouta 1 , J. Rocha 2 , G. Minas 2
1 Physics, Universidade do Minho, Braga Portugal, 2 Industrial Electronics, University of Minho, Guimarães Portugal
Show AbstractMicrofluidic technology is an important tool for analytical biochemistry applications. It enables the fabrication of the so called lab-on-a-chip. This technology offers inherent performance gains such as reduced sample size, shortened response time, and reduced costs. One of the main problems to overcome in lab-on-a-chip applications is to develop reliable and non-expensive systems allowing the proper mixing of fluids. To overcome long transit times due by diffusion and to enable high-efficient reactions it is necessary to induce the microfluidic system by a mechanism that accelerates the mixing and reaction, with no moving parts. Studies described in this paper aims the incorporation and validation of the use of a piezoelectric polymer Poly(Vinylidene Fluoride) in its phase, β-PVDF, in a fully-integrated disposable lab-on-a-chip for point-of-care testing and monitoring of biochemical parameters in biological fluids. With the deposition of the polymer underneath the microfluidics structures, acoustic microagitation can be obtained through electrical actuation, which leads to the enhancement of mixing and reaction time without moving parts. The application of acoustic microagitation through the β-PVDF piezoelectric polymer is advantageous when two or more fluids need to be mixed. It accelerates the mixing time resulting in a quicker complete and homogeneous reaction of the reactants and improving the global performance of the analysis that is being performed.The lab-on-a-chip concept and design presented in this paper offers a novel approach for clinical analyses, especially in biological fluids analyses, due to its portability, thus ensuring that the analysis can be performed at any location with instantaneous results. The lab on a chip performance was successfully demonstrated in the quantitative measurement of uric acid in human urine, thought other molecules or biological fluids can be also measured.With the optimization tests, was proved that is possible to use lower frequencies than resonance with no major changes in the mixing process.The effect of area, thickness and location within the lab-on-a-chip of the microagitation system was optimized and will be discussed. The optimization of the transparent conductive oxides for signal adquisition will be also adressed.ACKNOWLEDGMENTSupport for this research was provided by the Portuguese Foundation for Science and Technology (grants PTDC/BIO/70017/2006 and PTDC/CTM/69362/2006).
9:00 PM - FF9.18
Control of Channel Doping Concentration for Enhancing the Sensitivity of ‘Top-down’ Fabricated Si Nanochannel FET Biosensors.
Chan Woo Park 1 , Chang-Guen Ahn 1 , Jong-Heon Yang 1 , In-Bok Baek 1 , Chil Seong Ah 1 , Ansoon Kim 1 , Tae-Youb Kim 1 , Gun Yong Sung 1
1 Biosensor Research Team, ETRI, Daejeon Korea (the Republic of)
Show AbstractAlthough the ‘top-down’ technology for fabricating the field effect transistor (FET)-type Si nanochannel biosensors is a good candidate for overcoming some intrinsic limitations of the ‘bottom-up’ approach, it requires more efforts to pattern nanometer-scale dimensions comparable to those obtained by the ‘bottom-up’ process (typically a few tens of nanometers in diameter), which is considered crucial for achieving a high sensitivity. In the Si nanochannel FET sensor, the conductivity of a Si channel is modified by the binding of charged target molecules to the channel surface functionalized with specific receptor molecules, as the concentration of charge carriers within the Si channel varies in response to the electric field induced at the channel surface. Therefore, for a given amount of charged molecules bound to the channel surface, the sensitivity of a Si nanochannel FET sensor depends not only on the width of nanochannels but also on the doping concentration, where the sensitivity is higher at a lower doping concentration. As the doping concentration can be more easily controlled in the ‘top-down’ process (simply by adjusting the dose of the ion implantation process), the reduction of doping concentration can make up for the drawback of the ‘top-down’ process mentioned above. Here, we provide a quantitative analysis on the sensitivity of ‘top-down’ fabricated Si nanochannel FET biosensors as function of both the channel width and doping concentration, and demonstrate a practical strategy for achieving high sensitivity with less effort to reduce the channel width. In the present work, 100-nm to 500-nm-wide Si channels have been patterned on 40-nm-thick p-type silicon-on-insulator (SOI) layers doped from 1e17 to 2e18cm-3, and configured as FET structure where heavily doped source and drain regions are formed at both ends of the Si channel. For analyzing the sensitivity of nanochannel FETs in response to the variation of surface charges, they have been characterized as hydrogen ion sensors by monitoring the channel conductance within a buffer solution with pH values varying from pH 5 to 8. Within the range of the channel width and doping concentration employed in this work, the sensitivity (the pH 8/pH 5 current ratio) of Si channels has been observed to depend more strongly on the doping concentration than the channel width. Therefore, in the ‘top-down’ fabrication of Si nanochannel FET sensors, the reduction of doping concentration can provide a more effective way to obtain a properly high sensitivity, as a trade-off for difficulties in forming Si channels as narrow as those produced by the ‘bottom-up’ process. Based on such observations, the performance of Si FET sensors for detecting the prostate specific antigen (PSA) is also being investigated, and a quantitative report on the beneficial effect of low doping concentration for the detection of real proteins will be presented.
9:00 PM - FF9.19
High Affinity Selection of scFv Antibodies to the Monokine Induced by Interferon Gamma for use with BioFETs.
Theodore Nicholson 1 2 , Samit Gupta 1 2 , Edward Eteshola 2 , Stephen Lee 1 3 2
1 Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States, 2 Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States, 3 Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio, United States
Show AbstractCurrent methods of detection for biomolecules require a large volume of material. Whether it is blood, stool, or urine, large quantities are required and this can cause patient discomfort. Another drawback of current technology is the low levels of sensitivity. To overcome these obstacles several new methods are being investigated. In biologically sensitive FET sensors (BioFETs), protein analyte is localized proximal to sensing channel surface by specific biological recognition (affinity) elements (peptide, receptor, antibody, etc.), deployed on the sensing surface. The affinity elements act as “receptors”, and analyte binding to those receptors alters FET conductivity. Current biosensors are configured as biological field effect transitors (bioFETs) and exploit the high sensitivity and specificity of biomolecules (such as proteins and antibodies) in order to augment current gaining information about binding. These bioFETs can achieve picomolar or nanomolar specificity. Single chain fragment variables (scFvs) are much smaller than their antibody counterparts, but maintain full antigen recognition. This can allow for their use with the bioFET devices because of the increased proximity of the antigen to the sensing surface allowing the charge shielding effects of the layers of ions to be negated. This is accomplished by bringing the analyte well within the Debye length. Our work will be to generate high affinity scFv antibodies from the Tomlinson J library for use with a bioFET for detection of highly pertinent biomolecules (i.e., MIG, interferon alpha, etc.). We will show the differences in KD between our current method and our previous method that did not select for high affinity scFv antibodies. We will also demonstrate the increased specificity and response time of devices functionalized with the higher affinity scFv antibodies. BioFET technology is applicable in several disease states and can open the door to specific immune cell recruitment to the graft site in transplant rejection. In the future we see this technology being incorporated in clinical applications.
9:00 PM - FF9.2
Nanochannels Fabricated in Polydimethylsiloxane using Sacrificial Electrospun Polyethylene Oxide Nanofibers.
Leon Bellan 1 , Elizabeth Strychalski 2 , Harold Craighead 1
1 AEP, Cornell University, Ithaca, New York, United States, 2 Physics, Cornell University, Ithaca, New York, United States
Show AbstractUsing sacrificial electrospun polyethylene oxide (PEO) fibers, we have formed nanofluidic channels in polydimethylsiloxane (PDMS). Electrospinning is the process of forming nanofibers from a polymer solution using an electrically forced fluid jet. These fibers can be used as lithographic masks or sacrificial structures to form nanoscale features in other materials. In this work, electrospun fibers were deposited onto a silicon chip, and PDMS was poured on top and allowed to cure. The PEO fibers were removed from the cured PDMS by soaking the material in water, leaving nanochannels. We demonstrated that these nanochannels can be easily integrated with standard microfluidics by depositing fibers on patterned silicon chips. Imaging the channel cross-sections using a scanning electron microscope revealed the channels to have sub-micron diameters. To ensure that the channels were open, we filled them with fluorescent dye and imaged the filled channels. We also introduced single molecules of λ DNA into the channels, demonstrating the utility of these integrated micro- and nanofluidic structures for single molecule observation and manipulation. Using this nanofabrication technique, it is possible to fabricate hybrid micro- and nanofluidic PDMS structures without using lithography. These fluidic structures could be used for several purposes ranging from separating and analyzing biomolecules to forming materials with artificial vascular structure. Of the materials used to form microfluidic structures, PDMS remains one of the most popular due to its versatility and ease of use. Similarly, PEO is one of the most popular materials to electrospin because it is easy to work with, water soluble, and non-toxic. A fabrication process that combines these two materials is advantageous because the materials systems involved are well characterized and commonly used. Moreover, it should be straightforward to scale up this fabrication process to allow high throughput formation of micro- and nanoscale devices.
9:00 PM - FF9.20
Surface Modification and Micropattern Fabrication of Poly(dimethlysiloxane) by X-ray Lithography.
Je Won Yoo 1 , Soeun Chang 1 , Byung Mook Weon 1 , Ming Li 2 , Jong Hoon Hahn 2 , Jung Ho Je 1 , Yeukuang Hwu 3 , Giorgio Margaritondo 4
1 X-ray Imaging Center, Department of Materials Science and Engineering, POSTECH, Pohang, Gyungbuk, Korea (the Republic of), 2 Department of Chemistry, POSTECH, Pohang, Gyungbuk, Korea (the Republic of), 3 Institute of Physics, Academia Sinica, Taipei Taiwan, 4 School of Basic Sciences, Ecole Polytechnique Fadarale de Lausanne, Lausanne Switzerland
Show AbstractPoly(dimethlysiloxane) (PDMS) has been extensively studied as soft materials for biotechnological applications of lap-on-a-chips, bio-MEMS, and biomedical devices (1), because of soft, flexible, transparent, biocompatible, and mechanically durable properties (2, 3). However, the hydrophobic and chemically inert nature of PDMS makes difficulties in further applications. The hydrophilicity of the surface is required for microfluidic applications based on aqueous solutions through surface modification (3). The micropattern fabrication of PDMS architectures is often limited to time-consuming and costly techniques such as photolithography. To overcome the difficulties, we suggest a simple, versatile method which is based on X-ray lithography for simultaneous surface modification and micropattern fabrication. We show a successful fabrication of hydrophilic micropatterns using hard X-rays (10-60 keV) from a synchrotron source. We reveal that the hydrophilicity and the volume collapse occur and may originate from the oxidation of PDMS, which is characterized by contact angle measurement and FT-IR. We are able to fabricate a variety of hydrophilic micropatterns of PDMS which are easily controlled by mask and irradiation time, offering a simple, versatile method for further biotechnological applications of PDMS.References:(1) S. R Quake, Science 290, 1536 (2000).(2) H. Makamba, et al. Electrophoresis 24, 3607 (2002).(3) G. M. Whitesides, Nature 442, 368 (2006).
9:00 PM - FF9.21
Multifunctional Surface Coating for Biomolecule Immobilization.
Matthew Morgan 1 , Lawrence Brott 1 , Rajesh Naik 1
1 Nanostructured and Biological Materials Branch, Materials and Manufacturing Directorate, Wright-Patterson Air Force Base, Ohio, United States
Show AbstractCovalent attachment of biological compounds is essential in creating sensors and nanoscale devices. Currently, the use of succinate and glutaraldehyde coupling chemistries limits the types of compounds that can be attached to the surface. For example, gluteraldehyde only reacts with primary amines while succinate targets molecules rich in carboxyl groups. By using a strained epoxide group, surface immobilization on glass, quartz or silicon can be extended to include biomolecules with either thiol, amine, or carboxylate groups. We have developed a general approach for functionalizing and patterning surfaces with an assortment of diverse bio-molecules, inorganic particles, and polymers via novel surface chemistries involving highly reactive expoxide surface groups. Immobilization of horse radish peroxidase, functionalized quantum dots, and antibodies are demonstrated using this approach. Additionally, reaction kinetics, coupling efficiencies, surface coverage/biomolecule density will be investigated.
9:00 PM - FF9.22
Interaction of Quantum Dots with Collagen Immobilized Surfaces in Microfluidic Device.
Jungjin Park 2 1 , Silvia De Paoli Lacerda 2 , Dharmaraj Raghavan 1 , Alamgir Karim 2
2 Polymers Division, NIST, Gaithersburg, Maryland, United States, 1 Department of Chemistry, Howard University , Washington, District of Columbia, United States
Show AbstractCollagen is an important protein of the extracellular matrix (ECM) that provides mechanical support to cells and tissues in addition to performing various other important functions. A study of nanoparticle-collagen interactions is important because the interactions of nanoparticles with proteins has potential to disrupt essential biological processes such as cellular adhesion and protein assembly. The adsorption behavior of water soluble CdSe/ZnS core-shell quantum dot nanoparticles functionalized with carboxylic acid terminated organic ligand on collagen immobilized surface as well as biomimetic (amino-silane) model surface has been investigated. Collagen thin films were immobilized on the hydrophobic octadecanethiol (ODT) layer at pH 5.4 via a polydimethylsiloxane (PDMS) microfluidic device while the biomimetic model surface consisted of self-assembled monolayer (SAM) with amine terminal groups. The kinetics of nanoparticles adsorption on both collagen immobilized and the model surface (25 °C, pH 7.4) was followed by surface plasmon resonance imaging (SPRi) and quartz crystal microgravimetry (QCM) and characterized as well by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and confocal fluorescence microscopy. The binding constants governing nanoparticle adsorption on the model surface was determined by Langmuir adsorption measurements and found to strongly depend on particle-substrate chemistry and solution pH. The effect of varying solution pH on nanoparticle desorption was also investigated in order to gain insight into the role of electrostatic forces on nanoparticle-surface interaction. Our study shows that nanoparticle retention on both surfaces was higher under neutral pH conditions than either acidic or basic pH conditions.
9:00 PM - FF9.23
DNA Translocation Through a Novel Platform of Artificial Nanopore Array by Fine-tuning Pore Size via Atomic Layer Deposition (ALD).
Zhu Chen 1 , Yingbing Jiang 2 , David Adams 2 , Carter Hodges 2 , Nanguo Liu 1 , C. Brinker 2 1
1 , University of New Mexico, Albuquerque, New Mexico, United States, 2 , Sandia National Laboratories, Albuquerque, New Mexico, United States
Show AbstractAchieving single-molecule analysis such as detecting biopolymers (like DNA and RNA) translocation through membrane channels has always been a huge interest in biology. We developed a novel platform of nanopore array combining Evaporation-Induced Self-Assembly (EISA) of ordered nanoporous films with Focus-ion-beam (FIB) technique and apply patch clamp to detect DNA translocation through the nanopore array, represented by occurrence of current blockages. This new approach is advantageous over the conventional biological nanopores (like α-hemolysin) approach for the high stability over a wide range of mechanical, chemical and electrical conditions. Meanwhile, the unique platform of nanopore array and the capability to achieve very small pore size by simple EISA process provide advantages over the normal single solid-state nanopores on potential application in biopolymer detection and separation. In this talk, we apply Atomic Layer Deposition (ALD) technique to fine-tune the 2.6nm pore size of our nanopore array and demonstrate that DNA translocation behavior can be dramatically influenced by pore size effect. First, for ds-DNA, by homogenously depositing a layer of TiO2 (~0.35nm in decreasing the pore diameter) on pore surface, the velocity of DNA translocation is dramatically slowed down, comparable to that of biological nanopore system, due to the enhanced hydrodynamic friction inside the pores with smaller pore size. Continuous depositing another layer of TiO2 totally suppress the occurrence of current blockage as the pore size has been tuned smaller than 2nm ds-DNA diameter. Second, when one layer of (3-Aminopropyl)trimethoxysilane (~1.4nm in decreasing the pore diameter) is deposited on original 2.6nm pore surface, ss-DNA (homopolymer in this case) successfully translocate through the pore, indicated by the observation of current blockages, while ds-DNA translocation are still suppressed. Our results discover, for the first time, some very interesting DNA translocation features at very small pore size range which may be of great interests in the following two aspects: DNA sequencing by effectively slowing down the translocation velocity; fast purification of ss-DNA from ds-DNA or vise versa by one-step membrane separation process.
9:00 PM - FF9.24
Removal of Viruses from Water by Metal Oxide Nanoparticles.
Xuan Li 1 , Leonardo Gutierrez 2 , Helen Nguyen 2 , James Economy * 1
1 Materials Science and Engineering , University of Illinois at Urbana-Champaign, Urbana , Illinois, United States, 2 Civil and Environmental Engineering , University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
Show AbstractMicrobial contamination of drinking water is a serious problem of global significance. Development of nanoparticles as viricidal materials is of technological and scientific importance. Nanoparticles with high surface areas and ultra small particle sizes have dramatically enhanced efficiency and capacity of virus inactivation, which cannot be achieved by their bulk counterparts. A series of metal oxide nanoparticles coated on glass fiber substrates was developed in our research group for evaluation of its viricidal activity. We also carried out XRD, TEM, SEM and Zeta potential characterization, as well as surface area measurement. MS2 virus inactivation experiments showed that these nanoparticle coated glass fibers were extremely powerful viricidal materials.
9:00 PM - FF9.25
Cell Attachment and Proliferationon Undoped and Heavily Boron-Doped Polycrystalline Diamond.
Maryam Tabrizian 1 , Charles Agnes 2 3 , Fereshteh Azari 1 , Franck Omnes 2 , Pascal Mailley 3 , Philippe Bergonzo 4 , Slimane Ghodbane 5
1 Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada, 2 Neel Institut , CNRS Grenoble, Grenoble France, 3 INAC, CEA, Grenoble France, 4 LIST, CEA, Saclay France, 5 , Rho-BeSt, Innsbruck Austria
Show AbstractDiamond as a biocompatible material has great potential for in vivo applications. Diamond surface functionalization with the view of bio-transducer applications can be performed to date either by the mean of photochemical process of the initially H-terminated diamond surface (1) or by electrochemical assisted grafting with diazonium salts (2,3). The recent developments of boron doped conductive diamond have further increased the scale of diamond applications including electrode, sensors and detectors etc. Additionally, mechanical properties of diamond make it suitable for the optical or electrical monitoring of cell activity (4). In order to investigate cell responses to diamond, in-vitro studies were carried out on polycrystalline diamond, undoped and boron-doped, using pre-osteoblast (MC3T3-E1). The surface properties such as roughness, boron content and contact angle were determined for each diamond samples. Then preliminary biocompatibility was assessed by adhesion and proliferation of pre-osteoblast cells on undoped and boron-doped polycrystalline diamond. Cells were seeded with density of 5 x 10^4 cells/cm^2 on samples and incubated at 37 °C for 1, 2 , 4 hours and 3, 7, 11 days. After each time point medium was removed and cells were washed with PBS. Subsequently number of cells measured by Quick cell proliferation kit. Undoped and boron-doped polycrystalline diamond with different B-doping levels showed different surface roughness and wettability behavior. Further on, the adhesion and growth of pre-osteoblast cells have been studied in cultures on polycrystalline diamond substrates. In vitro cell tests of diamond samples revealed no cytotoxicity effect of these surfaces. Cells showed ability to attach and proliferate on both undoped and boron-doped diamond with different roughness values. The amount of cells attached to the samples after 1, 2 and 4 hours increased with increasing time; however pre-osteoblasts adhesion was significantly higher on nano grain size diamond compare to micro grain size samples. The growth rate of cells at 3, 7 and 11 days on diamond samples showed a consistent pattern with attachment. The interactions of biomolecule and cell with surface are known to be influenced by surface features respect to surface hydrophobicity, roughness, charge and composition. Since the degree of wettability is different in various grain faces in polycrystalline material, this could explain increased cell adhesion and proliferation observed on nanocrystalline diamond.References:1. Yang W, et al., Nat. Mater. (2002), 1, 2532. Bonnauron M, et al., Materials Research Society Symposium Proceedings (Ed: Bergonzo P, Gat R, Jackman RB, Nebel CE) (2007), 956, 81-873. Nebel CE, et al., J. of Physics D (2007) 40, 64434. Chong KF, et al., Langmuir (2007) 23, 5615-5621
9:00 PM - FF9.27
The Role of Ions in Controlling the Switching Mechanisms for Biosensors based on the Organic Thin Film Transistor Architecture.
Xiaojing Zhou 1 2 , Kathleen Sirois 1 , Daniel Elkington 1 , Warwick Belcher 1 , Paul Dastoor 1 2
1 Centre for Organic Electronics, University of Newcastle, Newcastle, New South Wales, Australia, 2 Physics, University of Newcastle, Newcastle, New South Wales, Australia
Show AbstractTwo types of organic thin film transistors have been successfully fabricated using an all solution-based fabrication scheme, in aim to developing an ultra sensitive and integrated biosensors. One type of transistor exhibits a moisture mediated field-effect like current-voltage characteristics, with the controlled gate voltages between +0.3 to -1 V. The second type of transistor is mediated by a high concentration of solid ions LiClO4 added to the insulating dielectric layer, with a switch-on voltage between -2 to -3 V. Interestingly, a large current amplification over 100000 is only obtained for the second type of transistor. Two different types of current modulation mechanisms are proposed and examined to explain their device characteristics. Their sensing abilities have also been investigated by embedding a glucose oxidase enzyme into these two types of transistors.
9:00 PM - FF9.28
Single Chirality Carbon Nanotube Purification by DNA Recognition.
Xiaomin Tu 1 , Ming Zheng 1
1 , DuPont Central Research and Development, Wilmington, Delaware, United States
Show Abstract9:00 PM - FF9.29
Fabrication of Individually Addressable Polypyrrole Microcontainers Using a Micropipette.
Ji Tae Kim 1 , Chang Mo Jeong 1 , Jung Ho Je 1 , Yeukuang Hwu 2 , Giorgio Margaritondo 3
1 X-ray Imaging Center, Department of Materials Science and Engineering, Pohang University of Science and Technology, Pohang Korea (the Republic of), 2 Institute of Physics, Academia Sinica, Taipei Taiwan, 3 School of Basic Sciences, Ecole Polytechnique Fadarale de Lausanne, Lausanne Switzerland
Show AbstractConducting polymer micro- and nano-structures are emerging as an attractive material in modern technology. They have a variety of potential applications in electronics (1), photonics (2), and biomedical science (3) because of their electrical and optical properties similar to metals or semiconductors while retaining flexibility, ease of processing, and biocompatibility. In particular, microcontainers of conducting polymer, which have additional outstanding properties of low density and large specific area, can be applied for bio-sensor, catalyst, and drug delivery systems (4-5). In general, microcontainers are fabricated with hard template method that is a coating process on template particles. This method yields well-defined grown structures but involves complicated and destructive procedures (4). A recently developed template-free approach, in which H2 bubble template is produced by the electrolysis of water, offers easy formation and removal of the bubble template (5). The location of microcontainers is however uncontrollable owing to the random distribution of the bubbles. Controlled growth, more specifically, patterning of microcontainers has yet to be developed for advanced applications.In this study we present a novel strategy to fabricate individually addressable polypyrrole (PPy) microcontainers, based on using a micropipette as a fountain pen. The key idea is to control the bubble nucleation site by positioning the micropipette on a desirable site. To control the microcontainer size for uniform patterning, we study the bubble growth mechanism in a micropipette, using real-time microradiography with coherent X-rays. We demonstrate successful fabrications of various types of patterned PPy microcontainers. We expect that our strategy could be also applied to individual modification of the chemical property of grown structure that is essential for multi-functional bio-sensors or drug delivery devices.*
[email protected]:(1) A. G. MacDiarmid, Angew. Chem. Int. Ed. 40, 2581 (2001).(2) R. H. Friend, et al. Nature 397, 121 (1999).(3) M. R. Abidian, et al. Adv. Mater. 18, 405(2006).(4) S. L. Tao and T. A. Desai, Adv. Mater. 17, 1625 (2005).(5) V. Bajpai, et al. Adv. Funct. Mater. 14, 145 (2004).
9:00 PM - FF9.3
The Fabrication and Characterization of Electrically Addressable Microfluidic Electrowetting Channels.
Seyeoul Kwon 1 , Jungwon Park 1 , Philip Rack 1 , Manjeet Dhindsa 2 , Jason Heikenfeld 2 , Anatoli Melechko 3
1 Materials and Science Engineering, University of Tennessee, Knoxville, Tennessee, United States, 2 Electrical and Computer Enginnering, University of Cincinnati, Cincinnati, Ohio, United States, 3 Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States
Show AbstractAn electrowetting microfluidic platform designed for multidimensional separation of ions and polar species has been fabricated on passive electrode as well as an active matrix thin film transistor arrays. Electrically addressable vertically aligned carbon nanofibers (VACNFs) were used as nanoscale functional elements of the platform. The materials integration issues of the passive and active devices and the fabrication procedures will be demonstrated. To gate and separate ions and polar species, VACNFs at various spatial separation have been synthesized on electrode arrays by catalytic DC plasma-enhanced chemical vapor deposition and were up 15 um tall. Subsequently the VACNFs have been insulated with various conformal layers of insulators deposited by chemically vapor and atomic layer deposition in order to compare the electrowetting characteristics. The electrostatically induced fluidic activity can Debye screen aqueous ions or control the flow of polar/non polar species depending upon functionalization of the nanofiber arrays. Various schemes of electrofluidic testing of passive electrode arrays will be demonstrated along with preliminary screening results. Finally, the process flow and device characteristics of VACNFs integrated on a thin film transistor array will be elaborated and a programmable multidimensional separations platform will be discussed.
9:00 PM - FF9.30
Plasma-enhanced Synthesis of Thin Fluoropolymer Layers with Low Raman and Fluorescence Backgrounds.
Hongquan Jiang 1 , Muhammad Jantan 1 , Sorin Manolache 1 , Ferencz Denes 1 , Max Lagally 1
1 , University of Wisconsin-Madison, Madison, Wisconsin, United States
Show AbstractRaman spectroscopy (RS) is becoming firmly established as an essential method in the life sciences, as it offers information not readily obtainable from other methods. The Raman effect is inherently weak, making the characterization of analytes at low concentrations difficult and subject to the influence of background and noise. In addition to efforts to increase Raman sensitivity via surface enhancement of the signal, the development of Raman substrates that limit background is of considerable current interest for conventional RS, where one analyzes a droplet of fluid deposited on a hydrophobic macromolecular substrate, which causes analyte concentration enhancement during drying. We describe a simple and inexpensive way, radio-frequency (RF) plasma enhanced chemical vapor deposition (PECVD), to provide substrates with extremely low background signal for a range of wavelengths useful in such RS studies.By taking advantage of the plasma-induced fragmentation of low-molecular-weight perfluorinated-hydrocarbon volatile starting materials and the subsequent recombination of the charged and neutral fragments on the surfaces that confine the plasma, we make chemically inert perfluorinated-hydrocarbon thin films [1]. These films, whose thickness is controllable to be as thin a several nm, adhere very strongly to the substrate and exhibit thermal stability, a low coefficient of friction, a low dielectric constant, and, at the lowest thicknesses, backgrounds almost indistinguishable from that of the bare (stainless steel, glass, other metals) substrate. We describe the synthesis of these thin films, discuss their properties, and contrast them with the properties of conventionally used spin coated films. We show the use these ultra-low-background substrates to test analyte concentration and thickness sensitivity limits using various approaches and analytes.Supported by DOE1. Jiang, H.Q., Jantan, M. K., Manolache, S., Denes, F. S., Lagally, M.: “Plasma-enhanced synthesis of thin fluoropolymer layers with low Raman and fluorescence backgrounds” (Langmuir, accepted, 2008)
9:00 PM - FF9.31
Plasma Processing of Nanostructured Polymeric Surfaces for the Development of Immunosensors.
Andrea Valsesia 1 , Pascal Colpo 1 , Ilaria Mannelli 1 , Giacomo Ceccone 1 , Francois Rossi 1
1 , European Commission JRC, Ispra Italy
Show AbstractImmunosensors play a very important role for the development of Point-of-Care analysis thanks to their rapid and sensitive detection capabilities. Among others, the control of the interface between the transducer and the biological probes is a crucial issue since the bio-interface is the essential element that guaranty the bioactivity of the immobilized biological probes. The control of the bio-interface is typically addressed by functionalizing the surface with chemical groups that interact properly with the proteins immobilized. Besides, new nanobiotechnology-based tools have led to more sophisticated approaches that use for instance nanostructured surfaces. Benefits have been already shown in many publications in terms of densification of protein nano-arrays and as well in terms of the improvement of immunoreaction efficiency. In this work we propose a new method for fabricating nanostrucured surfaces combining the use of colloidal masks with different plasma processes. This technique is extremely flexible in terms of the chemical nature, the function of the nanopattern and its physical and geometrical properties. In this method, Plasma Polymerization Processes are able to produce pinhole-free functional layers with different properties. The choice of the precursor together with the appropriate plasma processing parameter ensures the production of stable functional layers which can be used for the production of the chemically contrasted nanopatterns.Also the deposition of the colloidal mask in a controlled way is essential: for example, mass sensitive detectors (like Quartz Crystal Microbalance, QCM) require the use of very large areas in order to obtain measurable signals. Also plasma etching plays a very important role: it is important to choose the suitable processing parameters enabling the fabrication of nanostructured surface which are not limited in the patterning geometry and resolution.After the optimization of the nanofabrication process, the surfaces of immunosensors have been nanostructured. In particular we transferred the nanostructures on the crystals of QCM for on-line monitoring (time resolved) of the protein adhesion. The nanostructures accelerate the kinetics of absorption and increase the density of absorbed molecules, resulting in higher bioactivity of the immobilized proteins and consequently in an improvement of the immunosensing performances.
9:00 PM - FF9.4
Micro-patterning of Colloidal Crystals for Nanobiointerfaces.
Ana Ruiz 1 , Christopher Mills 2 , Andrea Valsesia 1 , Elena Martinez 2 , Josep Samitier 2 3 , Pascal Colpo 1 , Francois Rossi 1
1 Institute for Health and Consumer Protection, Joint Research Center. European Commission, Ispra, Varese, Italy, 2 Institute for Bioengineering of Catalonia (IBEC), Barcelona Science Park, Barcelona Spain, 3 Electronics Department, University of Barcelona, Barcelona Spain
Show AbstractA number of studies have investigated methods for the accurate positioning of nanometric beads on a substrate. The fabrication of such ordered microstructures has valuable applications in biosensing, optical and photonic band gap materials, and to study cell-surface interactions. Most of the methodologies used so far for the production of specific microstructures of colloidal crystals are based on template-assisted self-assembly; in which patterning and formation of the colloidal crystal take place simultaneously in a pre-defined template. On the other hand, methods for patterning the colloidal film after it has been formed have appeared recently and are based on the micro-patterning of nano-beads by soft-lithography lift-off processes. Such methods allow fine control over the microstructure of the colloidal film by selectively removing a single layer of close-packed nanoparticles. In this work, we use a recently developed top-down approach to produce bio-interfaces consisting in microarrays of nanostructures with bio-adhesive/bio-repellent contrast. The micro-patterning of nanoparticles has been achieved by nanoimprint-assisted contact stripping using poly(methyl methacrylate) (PMMA) stamps. The properties of PMMA with respect to hardness and flexibility are promising for resolving sub-micron patterns, and the use of the nanoimprinter allows careful control of the temperature and pressure during the removal of the nanoparticles. Patterns of polystyrene nano-beads in several micro-scale configurations have been obtained over large areas using beads of different diameters (100 ~ 1000 nm) and with different level of bead adherence to the substrate. Nano-scale chemical contrast has been produced inside the micro-patterns by nanosphere lithography and plasma-enhanced chemical vapor deposition of two polymers with different bio-activity. The bio-interfaces thus produced have been applied for enhanced biosensing and to examine cell-surface interactions at the nanoscale.
9:00 PM - FF9.5
Supramolecular Nanostamping of Coiled-Coil Protein Motifs.
Anna Laromaine 1 2 , Ozge Akbulut 1 , Arum Yu 1 , Muthu Murugesan 2 , Molly Stevens 2 , Francesco Stellacci 1
1 Materials and Engineering Science, MIT, Cambridge, Massachusetts, United States, 2 Materials and Institute of Biomedical Engineering, Imperial College, London United Kingdom
Show Abstract9:00 PM - FF9.6
Targeted Immobilization of Nanostructures and Biomolecules through Peptide-Based Biolinkers towards Nanosensing Platforms.
Marketa Hnilova 1 , Banu Taktak 2 , Ersin Oren 1 , Chris So 1 , Turgay Kacar 1 2 , Candan Tamerler 1 2 , Mehmet Sarikaya 1 2
1 GEMSEC, Department of Material Science and Engineering, University of Washington, Seattle, Washington, United States, 2 Molecular Biology and Genetics and MOBGAM, Istanbul Technical University, Istanbul Turkey
Show Abstract9:00 PM - FF9.7
Cells Culture on Viruses Based Scaffolds.
Jianhua Rong 1 2 , Gagandeep Kaur 1 , L. Andrew Lee 1 , Kai Li 1 , Charlene M. Mello 1 3 , Zhongwei Niu 1 , Qian Wang 1
1 Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, United States, 2 Department of Materials Science and Engineering, Jinan University, Guangzhou China, 3 Bioscience and Technology Team, US Army Natick Soldier Research Development & Engineering Center, Natick, Massachusetts, United States
Show AbstractCell behaviors are a complex orchestration of signaling between cell to cell and their surrounding extracellular matrix (ECM). Understanding the biological intricacies between the cell and ECM is critical to general biological questions and the design of functional scaffolds for tissue engineering. Patterning and aligning scaffolds at micro- and nano-scales with topographical features have been reported to influence cell responses. Viruses, such as tobacco mosaic virus (TMV), bacteriophage M13, cowpea mosaic virus (CPMV) and turnip yellow mosaic viruses (TYMV), can be considered as nature nanoparticles that provide highly promising possibilities in the construction of nanoscale materials with hierarchical ordering. These hierarchically assembled biomaterials offer a unique substrate or scaffold to investigate the cell response. In our group, we explored the natural tendency of rod-like virus, TMV and M13 viruses, to form 2D well-ordered films and 3D scaffolds, which were used to guide cell alignment and orient the cell outgrowth along defined directions. The human umbilical vein endothelial cell, NIH-3T3 mouse fibroblast and Chinese hamster ovarian (CHO) cell lines, were used to study the cell behavior on the virus based thin film and scaffolds. The results demonstrated that all the cells extend parallel to the band directionality of the virus, which shows that the method of controlling the alignment of cells with these new scaffolds based on rod-like virus is universal. And this concept can be utilized in similar fashion to other rod-like plant viruses and biocompatible polymers.In another study, we employed a 2D substrate coated with TYMV and TMV particles to investigate the role that the micro / nano environment plays on the differentiation pathway of bone marrow stromal cells (BMSCs) into osteoblasts. The temporal effect of TYMV coated substrate on the adhesion and differentiation capacity of the BMSCs was monitored for selected time periods of 7, 14 and 21 days. Comparing the gene expression pattern of BMSCs induced to osteogenic differentiation under standard culture conditions with the cells induced on TYMV and TMV substrates, we found significant differences in the temporal expression and level of expression of several key genes. Our findings indicate that TYMV, as a biogenic nanoparticle, can be employed as a model to modulate the nano-environment of the substrates in order to gain an insight into the role that the micro / nano environment has in regulating adhesion, growth and differentiation of BMSCs towards osteogenic lineage, which will be vital for designing compatible biomaterials for tissue engineering purposes.
9:00 PM - FF9.8
Manipulation of Gold Nanorod Surfaces with Self-Assembled Monolayers.
Seunghyun Lee 1 , Jason Hafner 1 2
1 Department of Chemistry, Rice University, Houston, Texas, United States, 2 Department of Physics and Astronomy, Rice University, Houston, Texas, United States
Show AbstractGold nanorods (NRs) exhibit tunable spectral peaks due to localized surface plasmon resonances (LSPR). Due to their strong extinction at near-infrared wavelengths, sensitivity to the optical properties of their environment and large near-field enhancements, gold NRs are being tested in a variety of biomedical applications.To improve their effectiveness, NRs surface chemistry can be modified with self assembled monolayers (SAM) and subsequent conjugation to biomolecules. SAM formation and displacement kinetics were monitored by tracking the LSPR peak wavelength, and the structure was probed by atomic force microscopy. The formation of SAM on gold NRs with well-defined nanometer-scale curvature and crystal orientation provides an avenue toward improved understanding of SAM formation kinetics. Here we have optimized the MHDA SAM formation on gold NRs, and found that the displacement of adamantanethiol by MHDA follows different kinetics from those found on flat gold films. We will also present an immunoassay based on gold nanorod LSPR and how these improved SAM formation protocols affect the sensor performance.
9:00 PM - FF9.9
DNA-Directed Nanoparticle Assembly onto Sub 30 nm Electron Beam Lithography Generated Nanopatterns.
Cecilia Lalander 1 , Udo Bach 1 2 , Scott Dhuey 3 , Stefano Cabrini 3
1 School of Chemisty, Monash University, Melbourne, Victoria, Australia, 2 , ARC Centre for Electromaterial Sciences (ACES), Melbourne, Victoria, Australia, 3 Molecular Foundry, Lawrence Berkley National Laboratory , Berkley, California, United States
Show Abstract
Symposium Organizers
Larry Nagahara National Cancer Institute
Thomas Thundat Oak Ridge National Laboratory
Sangeeta Bhatia Massachusetts Institute of Technology
Anja Boisen Technical University of Denmark
Kazunori Kataoka The University of Tokyo
FF10: Nanomaterial Formation and Interactions for Biomedical Applications
Session Chairs
Sangeeta Bhatia
Thomas Thundat
Thursday AM, December 04, 2008
Room 304 (Hynes)
9:00 AM - FF10.1
Stimuli Responsive PNIPAM – Gold Microcapsules for Cell Encapsulation.
Tatiya Trongsatitkul 1 , Bridgette Budhlall 1
1 Department of Plastics Engineering, University of Massachusetts, Lowell, Massachusetts, United States
Show Abstract9:15 AM - FF10.2
A Novel Self-assembled Drug Delivery Vehicle --- Helical Rosette Nanotubes.
Yupeng Chen 1 , Hicham Fenniri 2 , Webster Thomas 1
1 , Brown Univeristy, Providence, Rhode Island, United States, 2 , National Research Council and University of Alberta, Edmonton, Alberta, Canada
Show Abstract Today, conventional implant materials (such as micron-rough, nano-smooth titanium) are widely used in orthopedic surgeries. However, they are lagging in satisfaction to provide quick regeneration as well as sustained prolonged bone growth. One main reason is that osteoblasts along with bone and today’s implant materials fail to sufficiently integrate. To improve the biocompatibility of implant materials and bone regeneration, researchers have attempted to combine growth factors on or in implant materials, especially, novel nano-scaled materials. Helical rosette nanotubes (HRNs) are novel biomimetic self-assembled supramolecular structures whose basic building blocks are DNA base-pairs, which can be injected into the physiological environment as a liquid, and solidify into a viscous gel at body temperatures. HRNs are similar in size to collagen in cartilage. Previous studies have shown that HRNs are biocompatible and increase the adhesion of numerous cells compared to other commonly used orthopedic implant materials (like hydrogels and Ti). Especially, a variety of drugs (including growth factors and peptides) can be functionalized onto HRN side chains. Thus, it is hoped that HRNs can serve as a novel in situ curable, drug delivery device to improve osteoblast (bone-forming cell) adhesion and functions. In this study, the ability of HRNs and three short peptides (labeled for convenience: a or SNVILKKYRN, b or KPSSAPTQLN, and c or KAISVLYFDDS) chosen from bone morphogenetic protein-7 (BMP-7) to promote osteoblast (bone-forming cells) adhesion, proliferation and long-term functions were tested. In addition, the peptides were functionalized onto HRNs. The functionalized nanotubes were characterized by NMR, HPLC and SEM. Drug release kinetics were also tested. Importantly, results showed that the HRNs improved osteoblast bio-intergration with conventional implant materials (like Ti). In addition, the BMP-7 peptides released from HRNs enhanced osteoblast proliferation and long term functions. In this manner, this study provided an alternative tissue regeneration material which relies on nanotechnology that can deliver growth factors to improve cell function and can be injected as a liquid and solidify at body temperatures under short periods of time.
9:30 AM - **FF10.3
Understanding Silica Nanostructure Formation Using Natural Structures and Bio-inspired Techniques.
Mitchel Doktycz 1 3 , Mark Hildebrand 2 , Jonathon Sutton 3 , Scott Retterer 1 3 , Dave Allison 4
1 BioSciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States, 3 Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States, 2 , Scripps Institution of Oceanography, La Jolla, California, United States, 4 Department of Biochemistry & Cellular & Molecular Biology, University of Tennessee, Knoxville, Tennessee, United States
Show AbstractNatural systems excel in directing the synthesis of inorganic materials for various functional purposes. One of the better-studied systems is silica synthesis, as occurs in diatoms and marine sponges. The biological components involved in these processes are beginning to be identified. For example, various biological and synthetic polymers have been identified that can catalyze silica formation in vitro. However, the precise mechanisms of silica synthesis in vivo, and how complex 3-D structures are crafted, requires further investigation. Identifying structural intermediates, and correlating their formation with the genes and proteins involved, can help reveal the molecular details of this process. We are combining biological manipulation with advanced imaging tools to elucidate the synthesis of the silicified cell wall in various diatom species. Distinct silica morphologies are observed during formation of different substructures. Atomic force microscopy has been used to identify distinct silica ultrastructure that occurs in different regions of the mature diatom. A fundamental understanding of these processes is being furthered by attempts to replicate silica synthesis using bio-inspired approaches. Surface patterning of biomolecular templates offer a route to integrate conventional silicon patterning technologies with biologically based material synthesis. This combined fabrication technique enables controlled assembly over multiple length scales and an approach to understanding interfacial silica synthesis as occurs in natural systems. Together, the study of natural and synthetic silica structures are providing new insights into biosilicification processes and present opportunities for developing bio-inspired approaches to inorganic synthesis.
10:00 AM - **FF10.4
Synthesis and Functionalization of Nanocrystals and Nanocomposites for Biological Applications.
Jackie Ying 1
1 , Institute of Bioengineering and Nanotechnology, Singapore Singapore
Show AbstractNanocrystalline materials are of interest for a variety of applications. This talk describes the synthesis and functionalization of nanocrystalline and nanocomposite materials for biological applications. Specifically, we have generated metallic, metal oxide, and semiconducting nanocrystals for bioimaging, biolabeling, bioseparation and biosensing applications. These nanocrystals are ≤ 10 nm in size, and are surface modified to provide for high biocompatibility, colloidal stability, water solubility and buffer stability. We have also prepared bifunctional nanocomposite particles in the form of magnetic quantum dots. These materials can be tailored in both fluorescence and magnetic properties by manipulating their composition and particle size.
10:30 AM - FF10.5
Carbon Nanotube Structures for Cellular Photoacoustic Identification.
Charles Van Neste 1 2 3 , Larry Senesac 1 4 , Arpad Vass 1 4 , Thomas Thundat 1 4
1 , Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States, 2 , Oak Ridge Associated Universities, Oak Ridge, Tennessee, United States, 3 Electrical Engineering, Tennessee Technological University, Cookeville, Tennessee, United States, 4 Physics, University of Tennessee Knoxville, Cookeville, Tennessee, United States
Show AbstractWe report a new spectroscopic technique which allows the standoff identification of residues based on a photoacoustically actuated detector. We believe that this technique can be utilized to identify cellular structures which may help in the identification of cancerous verses non cancerous species. High Q, low cost, quartz crystal tuning fork resonators are used to monitor the intensity of light returning from a target. The light impinging on the tuning fork creates an acoustic wave which sets the device into resonance. By coating the tuning fork with nano structures, the sensitivity of the device can be greatly increased. Normal and cancerous mouse pulmonary cells are placed on a target sub-straight and illuminated with a quantum cascade laser approximately 1 foot away. Reverse photoacoustic spectra is taken and compared between the two cellular forms. We expect that a bulk difference between the cells will be observed.
10:45 AM - FF10.6
Functional Conducting Polymer Nanomaterials for Neural Interface Applications.
Mohammad Reza Abidian 1 , David Martin 1 2 3 , Daryl Kipke 1
1 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States, 2 Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan, United States, 3 Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan, United States
Show AbstractIn recent years, many scientific and technological efforts have been devoted to design and develop hybrid bionic systems that link, via neural interfaces. Neural prostheses have been developed to control motor disorders or to translate willful brain processes into specific actions by the control of external devices using microelectrodes. Clinical progresses of the numerous interface concepts proposed in basic research are limited by common recurrent problems, ranging from improper neuronal adhesion to inadequate signal stability. Neural microelectrodes transduce biologic signals to electronic signals in applications involves neural recording and/or micro-stimulation. Unfortunately, only a minority of the recording electrodes on these devices continue to function for long periods of time. The objective of this project is to develop biocompatible, functional conducting polymer nanomaterials and controlled drug delivery system to improve the material-neural tissue interface and long-term performance of the neural microelectrodes in vivo. We have developed a new approach for preparing drug-loaded conducting polymer nanotubes on surface of neural microelectrodes. The fabrication process includes the electrospinning of a biodegradable polymer into which a therapeutic agent has been incorporated followed by electrochemical deposition of conducting polymer. The wall thickness of the poly (3, 4- ethylenedioxythiophene) PEDOT nanotubes varied from 50-100 nm, and the nanotube diameter ranged from 100-600 nm. The in-vitro impedance spectroscopy and cyclic voltammetry of electrode sites revealed that the impedance significantly decreased about 2 orders of magnitude and the charge transfer capacity significantly increased about 3 orders of magnitude after PEDOT formation on the neural electrodes. By using electrical stimulation (as low as 0.5 V) we could precisely release therapeutic agent nerve growth factor (NGF) at desired points in time. After the electrical excitation we observed a significant increase in the amount of NGF released presumably either through the ends of PEDOT nanotubes or though openings or cracks on the surface of nanotubes created by actuation. These polymer-modified microelectrode arrays were implanted in barrel cortex of male rats and their performance was monitored by impedance spectroscopy, signal amplitude, and noise level over periods of at least 7 weeks. The polymer-coated sites were found to outperform control sites with respect to signal-to-noise ratio and impedance. We also fabricated aligned conducting polymer nanotubes (ACPN) that were loaded with NGF. Dorsal root ganglion explants, and PC12 cells were cultured on these ACPN. It was found that cells could be patterned and preferentially guided in the direction of the nanotube orientation. The Enzyme-Linked ImmunoSorbent Assay (ELISA) and PC12 cell culture experiments confirmed retained bioactivity of NGF during the fabrication process.
11:30 AM - **FF10.7
Nanostructured Materials and Their Direct Electron Transfer for Proteins.
Changming Li 1 , Shujuan Bao 1 , Chuxian Guo 1
1 School of Electronic & Electrical Engineering, Nanyang Technical University, Nanyang Singapore
Show Abstract12:00 PM - FF10.8
Electrochemical Aptamer Nanoarray for High Specific Small Chemical Assay.
HeaYeon Lee 1 , YeonSeok Kim 2 , ManBock Gu 2 , Tomoji Kawai 1
1 Institute for Scientific and Industrial Research(ISIR-SANKEN), Osaka university , Osaka Japan, 2 College of Life Sciences and Biotechnology, Korea University, Seoul Korea (the Republic of)
Show AbstractRecently, many research for in-vitro selections of aptamers that bind to specific target compounds have been reported. Aptamers are single-stranded nucleic acids, with or without modified nucleotides for additional chemical activity, that function like the antigen combining sites of antibodies. Aptamers are not restricted for the various targets, like proteins, peptides, amino acids, nucleotides, drugs, carbohydrates and other small organic and inorganic compounds. And also, in-vitro selected aptamers could be reproducibly synthesized and obtained economically. Aptamers can be modified with certain functional groups and is immobilized on many surfaces, both directly and indirectly, resulting in well ordered receptor layers. Thus, aptamers offer a useful alter native to antibodies as sensing molecules, especially in the development of biosensor for chemicals. In addition, it was known that DNA aptamers are more stable than RNA aptamers and easier to identify and handle. In this present, we describe ultraspecific electrochemical DNA aptamer chip based on nano-sized well array for small chemical sensing. DNA aptamers specifically binding to 17β-estradiol were selected by the SELEX (Systematic Evolution of Ligands by EXponential enrichment) process from a random ssDNA library, composed of approximately 7.2×1014 DNA molecules. Nanowell array chips were employed to evaluate the electrochemical signals generated from interactions between the aptamers and the small chemical molecules. When 17β-estradiol interacted with the DNA aptamer, the current decreased due to the interference of bound 17β-estradiol with the electron flow produced by a mediated redox reaction. Serial dilutions of 17β-estradiol in binding buffer solutions were found out that up to 17β-estradiol was detectable when 100 nM-1 pM concentrations were tested. In the negative control experiments with two small organic chemical (2-methoxynaphthalene and 1-aminoanthraquinone), there was only a slight change in the current and potential shift. It indicates the electrochemical aptamer nanoarray can be assay to chemical targets with sub-pM and astonishing specificities.
12:15 PM - FF10.9
Light Induced Vesicle Shape Changes and Destruction of Self-assembled Polymeric Vesicles Resulting from Co-encapsulation of Horse Spleen Ferritin and Porphyrin Dyes.
Gregory Robbins 1 , Masaya Jimbo 2 , Joe Swift 2 , Michael Therien 2 , Ivan Dmochowski 2 , Daniel Hammer 1 3
1 Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2 Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 3 Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Show AbstractPolymeric bilayer vesicles are ideal systems for studying self-assembled membranes and designing multi-functional biological therapeutics. Because they are up to 50 times tougher than analogous phospholipid based vesicles, they are ideal platforms in which to study the interactions of self-assembled structures with complex proteins. We co-encapsulated horse-spleen ferritin, a 24-subunit, iron-encapsulating protein, and porphyrin-based fluorescent dye in polymer vesicles. We show that exposure of these vesicles to fluorescent light of various wavelength leads to spontaneous shape changes and, in some cases, complete vesicle destruction. Additionally, we characterized the effect of protein encapsulation on both the elasticity and bending rigidity of the membrane using micropipette aspiration. We show protein localization and loading capacity using a variety of techniques including confocal microscopy, fluorescent recovery after photobleaching, and flow cytometry. Finally, we extended this study to other common proteins, BSA and myoglobin. This study indicates the depth of complex interactions that are possible in multiple component self-assembled systems, and it serves as a basis for rational design of smart materials for biological applications.
12:30 PM - FF10.10
Synthesis and Characterization of Tobacco Mosaic Virus Templated Inorganic Composite Fibers.
Jianhua Rong 1 2 , Zhongwei Niu 1 , Fiona Oberbeck 1 , Vaughn Braxtion 1 , Qian Wang 1
1 Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, United States, 2 Department of Materials Science and Engineering, Jinan University, Guangzhou China
Show AbstractPlant viruses and other biological particles can be considered as nature nanoparticles with the uniform shape and size. TMV is a classic example of a rod-like plant virus with 300 nm long, 18 nm in diameter and a 4-nm cylindrical cavity along the central core. Recent studies showed that the surface properties of TMV can be manipulated chemically or genetically without disrupting the integrity and morphology of TMV capsids, which make TMV an ideal template. The surface chemistry of TMV provides a structured substrate for the site-specific nucleation of a variety of inorganic solids, such as iron oxyhydroxides, CdS, PbS, gold, nickel, cobalt, silver, copper and iron oxides, and silica. In the case of silica mineralization, either at low pH or high pH, silica/TMV nanotubular superstructure can be formed. However, it is difficult to control the assembly structure into homogenous 1D long fiber. In this study, we prepared TMV/polymer/silica composite long fibers by using either native TMV or polymer/TMV composite fiber as the template. The TEM analyses have shown that the length of composite fiber can reach several microns. Furthermore, with silica as matrix, other inorganic functional components could be incorporated into such TMV-based 1D materials. For example, inorganic composite fibers with luminescent properties have been synthesized with lanthanides as dopants. The luminescent nanowires can be potentially used in sensing and photovoltaic applications. Similarly, doping magnetic cobalt oxide or iron oxide into the silica matrix will lead to magnetic composite nanowires. Such kind of 1D structure has great potential in the application including electronics, optics, sensing and biomedical engineering by a hierarchical self-assembly process.
12:45 PM - FF10.11
On the Incorporation Mechanism of Hydrophobic Quantum Dots in Silica Spheres by a Reverse Microemulsion Method.
Rolf Koole 1 , Matti van Schooneveld 1 , Jan Hilhorst 1 , Celso de Mello Donega 1 , Dannis 't Hart 2 , Alfons van Blaaderen 2 , Daniel Vanmaekelbergh 1 , Willem Mulder 3 , Andries Meijerink 1
1 CMI, Debye Institute, Utrecht Netherlands, 2 SCM, Debye Institute, Utrecht Netherlands, 3 , Mount Sinai School of Medicine, New York, New York, United States
Show AbstractIn the past decade, the incorporation of metal, semiconductor or insulating nanoparticles into silica spheres has been studied extensively. Silica coating offers several advantages related to potential applications. In the first place, silica may provide both chemical and physical shielding from the direct environment, thereby improving the stability. For example, it can prevent aggregation of the nanocrystals, reduce the release of (cytotoxic) ions, or prevent photo-oxidation in the case of quantum dots (QDs). In addition, a silica nanosphere can serve as a platform for including multiple functionalities in a single nanoparticle, for example for multi-modal imaging.In this contribution, we have elucidated the incorporation mechanism of hydrophobic semiconductor nanocrystals (or quantum dots, QDs) in monodisperse silica spheres (~ 35 nm) by a water-in-oil (W/O) reverse microemulsion synthesis. Fluorescence spectroscopy is used to investigate the rapid ligand exchange that takes place at the QD-surface upon addition of the various synthesis reactants. It is found that hydrolyzed TEOS has a high affinity for the QD surface and replaces the hydrophobic amine-ligands, which enables the transfer of the QDs to the hydrophilic interior of the micelles where silica growth takes place. By hindering the ligand exchange using stronger binding thiol-ligands, the position of the incorporated QDs can be controlled from centred to off-centre, and eventually to the surface of the silica spheres. Our incorporation mechanism explains how we can have high control over the incorporation of single QDs exactly in the middle of silica spheres. In conjunction with our findings, we were able to make QD/silica particles with an (unprecedented) quantum efficiency of 35 %. It is likely that the proposed mechanism also applies to the incorporation of other hydrophobic nanocrystals in silica using the same method.
FF11: Nanoparticles for In-vivo Bioimaging
Session Chairs
Thursday PM, December 04, 2008
Room 304 (Hynes)
2:30 PM - **FF11.1
Designing Quantum Dots for Biomedical Imgaging.
Moungi Bawendi 1
1 Department of Chemistry, MIT, Cambridge, Massachusetts, United States
Show Abstract3:00 PM - FF11.2
Targeting of His-tagged Proteins with Small Pegylated Quantum Dots with a Controlled Stochiometry.
Aurélien Dif 1 , Victor Roullier 1 , Fouzia Boulmedais 3 , Jacob Pielher 4 , Maxime Dahan 5 , Zoher Gueroui 2 , Valerie Marchi-Artzner 1
1 Chemistry department, University Rennes 1, CNRS, UMR 6226, Rennes France, 3 Institut Charles Sadron,, UPR 22 CNRS, Strasbourg France, 4 institut for Biochemistry, Johann Wolfgang Goethe university, franckfurt Germany, 5 Ecole Normale Supérieure , laboratoire Kastler Brossel, CNRS UMR 8552, Paris France, 2 Physic department, University Rennes 1, UMR 6251 CNRS, Rennes France
Show Abstract3:15 PM - FF11.3
Cadmium-free Quantum Dots for in Vivo Imaging.
Liang Li 1 , Toufic Jean Daou 2 , Myriam Protiere 1 , Isabelle Texier-Nogues 2 , Peter Reiss 1
1 INAC/SPrAM, CEA Grenoble, Grenoble France, 2 LETI/DTBS, CEA Grenoble, Grenoble France
Show AbstractThe intersection of nano-objects with biology has produced exciting perspectives that can profoundly impact biomedical research. Colloidal semiconductor nanocrystals (quantum dots) consisting of an inorganic core (1-10 nm) covered with a layer of organic ligands are appealing fluorescent labels for both in vitro and in vivo biological investigations. They combine unique optical properties, such as size-dependent fluorescence, high fluorescence quantum yield, large absorption band and enhanced photo-stability with respect to organic dye molecules. The NIR spectral window (650-900 nm) is appealing for in vivo optical imaging because of the low tissue absorption and scattering in this wavelength range. Therefore the design of high-quality NIR-emitting quantum dots, with outstanding optical properties in comparison to organic dyes, should lead to novel contrast agents with improved performance (higher fluorescence quantum yields and photo-stability). While certain types of cadmium and lead chalcogenide quantum dots show appropriate optical properties for in vivo imaging, they suffer from the low acceptability due to their intrinsic toxicity. Indium phosphide nanocrystals could be an interesting alternative provided that synthesis methods for the reproducible production of high quality samples are developed. We present novel wet-chemical routes to indium phosphide core, related core/shell and core/shell/shell nanocrystals. The obtained samples exhibit size-dependent fluorescence in the visible and near infrared spectral range (480-720 nm, FWHM 40-70 nm). Their quantum yield can reach 40-70% after the shell growth and an excellent photo-stability is observed. At the same time their hydrodynamic diameter remains small (sub-10 nm), which is of crucial importance for their bio-distribution. After transfer to the aqueous phase via surface ligand exchange, the potential of the obtained quantum dots for use in vivo imaging is evaluated. Our results show that the speed of first pass extraction of zwitterionic (cysteine)-coated InP/ZnS quantum dots towards the reticulo-endothelial system (liver, spleen, bone marrow) is strongly reduced as compared to anionic and cationic surface coatings, leading to a homogeneous bio-distribution.Finally, first promising results using a system so far unexplored for vivo imaging, namely ZnS capped copper indium sulfide (CIS) quantum dots, are presented.
3:30 PM - FF11.4
``Giant" Multishell CdSe Nanocrystal Quantum Dots with Suppressed Blinking: Novel Fluorescent Probes for Real-Time Detection of Single-Molecule Events.
Jennifer Hollingsworth 1 , Yongfen Chen 1 , Javier Vela 1 , Han Htoon 1 , Joanna Casson 1 , Donald Werder 1 , David Bussian 1 , Victor Klimov 1
1 Chemistry Division, Los Alamos National Lab, Los Alamos, New Mexico, United States
Show AbstractSemiconductor nanocrystal quantum dots (NQDs) are near-ideal fluorophores for biolabeling applications such as whole-cell tracking, sub-cellular compartment tracking, single NQD tracking within a live cell, and even single molecule tracking. Compared to alternative fluorophores, such as organic dyes, NQDs are characterized by significantly enhanced photostability and unique particle-size-tunable optical properties—efficient broadband absorption and narrow-band emission. Despite these enabling characteristics, NQD optical properties remain frustratingly sensitive to their surface chemistry and environment (e.g., aqueous as opposed to non-aqueous). The coordinating organic ligands used to passivate NQD surfaces are strong contributors to such bulk NQD optical properties as quantum yields (QYs) in emission. Ligand loss through physical separation or photochemistry results in uncontrolled changes in QYs and, in the case of irreversible and complete loss, in permanent “darkening” or photobleaching. In addition, NQDs are characterized by significant “blinking” (fluorescence intermittency) at the single NQD level. While a precise mechanism has yet to be universally accepted, blinking is generally considered to arise from an NQD charging process that results from interactions at the NQD surface or near-surface environment. Blinking is unacceptable for such applications as real-time monitoring of single biomolecules. We report for the first time that these key optical properties—QY, photobleaching and blinking—can be rendered independent of NQD surface chemistry and environment by growth of a very thick, defect-free inorganic shell.1 It has been previously reported that addition of an inorganic shell of a higher bandgap semiconductor material (e.g., ZnS onto CdSe) can enhance QYs and improve stability. However, the optical properties of such standard core/shell NQDs remain susceptible to ligand loss and changes in ligand identity through ligand-exchange reactions (e.g., for rendering NQDs soluble in water). In contrast, with our new approach we isolate the wavefunction of the NQD core from the NQD surface and surface environment and, thereby, create a fundamentally unique NQD that is structurally more akin to physically grown epitaxial QDs. Specifically, we demonstrate that our “giant” NQDs (g-NQDs) do not photobleach under continuous laser excitation and are insensitive to changes in surface chemistry. Critically, we show that g-NQDs exhibit markedly improved blinking behavior for enhanced imaging capability—to date, up to 40% of a given g-NQD sample is “non-blinking,” with >60% having high on-time fractions of >80%. We further discuss the relationship between these key optical properties and g-NQD shell thickness, composition and structure, as well as surface chemistry and chemical environment with an emphasis on biologically relevant media. [1] Y. Chen et al. J. Am. Chem. Soc. 130, 5026 (2008). Featured in “Nature Research Highlights,” 24 April 2008.
3:45 PM - FF11.5
Tracking Intracellular Transport of Nanoparticles by Quantum Dots.
Gang Ruan 1 , Amit Agrawal 2 , Shuming Nie 3
1 Chemical, Biomolecular and Biomedical Engineering, the Ohio State University, Columbus, Ohio, United States, 2 Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 3 Biomedical Enigneering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States
Show AbstractHow nanoparticles are transported inside live cells is an issue of considerable interest in many areas such as molecular imaging and drug delivery. Despite intensive research efforts on this subject, lack of understanding of the intracellular transport of nanoparticles remains a critical limiting factor in developing nanoparticle-based technologies for biomedical applications. We have used semiconductor nanocrystals (commonly known as quantum dots) as a prototype of nanoparticles, and tracked their motion in live cells by dynamic confocal imaging. Quantum dots were delivered into cells by either Tat peptide or streptolysin-O toxin. It was found that Tat-quantum dot conjugates were internalized by the cells via macropinocytosis. In the cytoplasm, Tat-quantum dots were encapsulated in vesicles, forming aggregates of nanoparticles, and were carried by motor proteins to a perinuclear region. In the vesicles the quantum dots were tethered to the inner vesicle surface. Part of the Tat-quantum dots was released from the cells by vesicle shedding. On the other hand, streptolysin-O delivery resulted in single (i.e. un-aggregated) quantum dots in the cytoplasm, as evidenced by the fluorescence intermittency of these quantum dots. The single quantum dots were recruited by motor proteins onto cytoskeletons, and transported to a perinuclear region. The quantum dots were also used to examine the mechanism of motor proteins in in vivo conditions. The above results, especially the comparisons between the results caused by the two different delivery approaches, have important implications for designing nano-sized constructs to probe living systems.
4:30 PM - FF11.6
Composite Materials of Polymers and Nanoparticles for Biological Imaging.
So-Jung Park 1 , Brenda Sanchez-Gaytan 1
1 Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Show AbstractFunctional nanoparticles and polymers have been sequestered and organized in block-copolymer assemblies to generate advanced multifunctional composite materials. The cooperative self-assembly of block-copolymers and quantum dots led to ordered arrangement of quantum dots at the spherical interface in well-defined block-copolymer aggregates. The quantum dots arranged at the interface were highly luminescent, and the number of incorporated quantum dots as well as their positions could be controlled by varying the molar ratio between the copolymers and quantum dots. Different sized quantum dots and iron oxide nanoparticles have been encapsulated in block-copolymer micelles for magnetic manipulation and multi-color biological detection applications. In addition to inorganic nanoparticles, light emitting conjugated polymers have been incorporated in block-copolymer micelles based on the same approach. Remarkably, the co-assemblies were extraordinarily bright, showing orders of magnitude higher fluorescence intensities than commercially available dye-labeled polymer particles. These optically and magnetically active composite particles with excellent optical properties are highly desirable in bioimaging applications, and they can be readily functionalized with biomolecules. Important factors affecting the co-assembly structure and the properties of their bioconjugates will be discussed in the presentation.
4:45 PM - FF11.7
Development of Nanophoshpors for NIR Fluorescence Bioimaging.
Kohei Soga 1 2 5 , Kimikazu Tokuzen 1 , Yoshihito Okumura 1 , Masao Kamimura 3 , Yukio Nagasaki 3 4 5
1 Dept. Mater. Sci. and Tech., Tokyo Univ. of Sci., Noda, Chiba, Japan, 2 PTRC, Tokyo Univ. of Sci., Noda, Chiba, Japan, 5 TARA, Univ. of Tsukuba, Tsukuba, Ibaraki, Japan, 3 Dept. Mater. Sci., Univ. of Tsukuba, Tukuba, Ibaraki, Japan, 4 TIMS, Univ. of Tsukuba, Tsukuba, Ibaraki, Japan
Show AbstractFluorescence bioimaging (FIB) is one of the most important tools for biomedical applications. Major problems on the imaging are color fading of the phosphor, autofluorescence, phototoxicity and strong scattering due to the use of the short-wavelength excitation light such as UV or visible light. Rare-earth doped ceramic materials are known as efficient fluorescence materials with near infrared (NIR) excitation. Nd:YAG laser, to emit 1064-nm light with 800 nm-excitation, and Er-doped optical fiber amplifier, to emit 1550-nm light with 980-nm excitation, are good examples. Another characteristic phenomenon of the RED-CNP is upconversion (UC) emission. The UC occurs in selected combination of the rare-earth ions and host materials through means of a stepwise excitation among the discrete energy levels of rare-earth ions. The authors have studied rare-earth doped ceramic nanophosphors (RED-CNP) to be applied for the UC-FIB and NIR-FIB, which use NIR excitation to avoid the above listed problems of the currently used FIB with UV to visible excitation. The first important issue of this study is to fabricate RED-CNP. One of the typical RED-CNPs is rare-earth doped yttrium oxide nanoparticles, which can emit both NIR and UC emission with NIR excitation. We combined homogeneous precipitation of hydroxyl carbonate precursor and sintering-inhibited calcination to produce mono-dispersed yttrium oxide nanoparticles in water. Surface modification of the RED-CNP with functional polymer is of the next importance to give dispersion stability in physiological condition and specific interaction of the particles with biological substances. We installed PEG based polymers on the surface of the yttrium oxide nanoparticles to achieve dispersion stability of the particles in physiological saline and to control the adsorption of the particles to proteins. The yttrium oxide particles with 100-200 nm size were stably dispersed under an physiological condition for more than 10 hrs. The specific interaction of the particles with proteins was tested by using plate assay. The particles only interacted with avidin plate. The dispersion stability and specific interaction of the particles were proofed. We also report the control of the dispersion stability of the phosphors in physiological condition by forming liposome containing the RED-CNP. Some demonstrative works of the NIR-FIB by using the RED-CNP will also be reported.
5:00 PM - FF11.8
Hybrid Fluorescent and Magnetic Water-soluble Micelles: Bioactivated Nano-probes.
Victor Roullier 1 , Fabien Grasset 1 , Olivier Cador 1 , Jacob Piehler 2 , Maxime Dahan 3 , Valerie Marchi Artzner 1
1 Chemistry , Université Rennes1 UMR 6226, Rennes France, 2 Biochemistry, Johann Wolfgang Goethe-Universität Frankfurt am Main, Institute of Biochemistry, Frankfurt Germany, 3 Kastler Brossel Laboratory, Ecole Normale Supérieure CNRS UMR 8552, Paris France
Show Abstract5:15 PM - FF11.9
Optically Active Metal Nanoparticle and Quantum Dot Co-Immobilization Using Genetically Engineered Peptides for Inorganics.
Turgay Kacar 1 2 , Mustafa Gungormus 1 , Marketa Hnilova 1 , Ersin Emre Oren 1 , Candan Tamerler 2 , Mehmet Sarikaya 1
1 Materials Science and Eng., University of Washington, Seattle, Washington, United States, 2 Molecular Biology and Genetics, Istanbul Technical University, Istanbul Turkey
Show Abstract5:30 PM - FF11.10
Immune Tolerance Induction Using Superparamagnetic Iron Oxide Nanoparticles.
Brian Larsen 1 , Natalie Serkova 2 , Howard Davidson 3 , John Hutton 3 , Conrad Stoldt 1
1 Mechanical Engineering, University of Colorado, Boulder, Colorado, United States, 2 Anesthesiology, University of Colorado Denver Health Sciences Center, Denver, Colorado, United States, 3 Barbara Davis Center for Childhood Diabetes, University of Colorado Denver Health Sciences Center, Denver, Colorado, United States
Show AbstractSuperparamagnetic iron oxide nanoparticles (SPIO) are prevalent in biomedical applications as magnetic resonance imaging (MRI) contrast agents. SPIO is typically biofunctionalized with a ligand, such as a monoclonal antibody, to label specific molecular targets in vivo for detection with MRI. While SPIO is extensively studied as diagnostic agents, few studies involve the use of SPIO as a drug delivery agent. In this study, the authors present an ovalbumin (OVA) SPIO complex to induce immune tolerance in OVA23-3 T-cell receptor (TCR) transgenic mice. This study utilizes OVA-SPIO complexes to tolerize OVA23-3 transgenic mice to OVA and is significant to research of autoimmune disorders, such as Type I diabetes, by extending SPIO enhanced MRI to study immune tolerization induction.SPIO as a drug delivery agent has many advantages. An SPIO complex can be detected in vivo as an MRI contrast agent to non-invasively track drug biodistribution and monitor efficacy of delivery. Furthermore, SPIO can be synthesized with specific surface chemistry and particle sizing for the desired biodistribution. An advantage specific to this study is the increased efficiency of antigen delivery to antigen presenting cells (APCs) by crosslinking antigen to a solid-phase nanoparticle, enabling antigen-SPIO complexes to be internalized via phagocytosis as opposed to liquid phase pinocytosis. Finally and importantly for drug delivery applications, SPIO is a biocompatible material and degradable into soluble iron chlorides.In this study the authors utilize 12nm SPIO synthesized from a solvothermal process that is an ideal size for intravenous delivery as it is large enough to avoid vascular extravasation and small enough to avoid hepatic clearance. The SPIO is amine-functionalized using an aminosilane (aminopropyldimethylethoxysilane) previously unused in SPIO studies which we have demonstrated condenses as a monolayer on the SPIO surface without interparticle crosslinking to maintain SPIO monodispersity. The SPIO is crosslinked to OVA at cysteine residues to maintain the integrity of the OVA 323-339 epitope recognized by the OVA23-3 TCR, and the resulting OVA-SPIO complex is delivered in vitro to splenocytes harvested from OVA23-3 transgenic mice.Results of OVA-SPIO incubation with OVA23-3 splenocytes in vitro demonstrate delivery of the OVA to APCs and presentation of OVA to T cells. Splenocytes incubated with increasing doses OVA-SPIO demonstrated increasing cellular proliferation and production of interferon-γ (IFN-γ) from recognition of the OVA 323-339 epitope by the OVA23-3 TCR. As a control, splenocytes incubated with a BSA-SPIO (bovine serum albumin) complex did not demonstrate increased proliferation or IFN-γ production. The authors will present in vitro results of this study and characterization of the SPIO delivery agent, including MRI, TEM, XRD, dynamic light scattering, zeta potential measurement, and OVA-SPIO biological properties.
5:45 PM - FF11.11
PEG-stabilized Manganese Oxide and Iron Oxide Nanoparticles for MRI Contrast Agents.
Hyon Bin Na 1 2 , Kwangjin An 1 2 , Yong Il Park 1 2 , Taeghwan Hyeon 1 2
1 School of Chemical and Biological Engineering, Seoul National University, Seoul Korea (the Republic of), 2 , National Creative Research Initiative Center for Oxide Nanocrystalline Materials, Seoul Korea (the Republic of)
Show AbstractMaterials within nanoscale size range have very unique and fascinating properties that are very different from their bulky counterparts. Much progress has particularly been made within the biological applications of nanoparticles. Inorganic nanoparticles have increasingly become the focus of attention for bioimaging agents for diagnosis. In particular, metal oxide nanoparticles in particular, have shown very promising possibilities as contrast agents of magnetic resonance imaging (MRI). High quality inorganic nanoparticles have been often synthesized by organometallic approaches. Since the synthesized particles are hydrophobic and inadequate for the aqueous environments of living organisms, and an additional process is required to disperse the nanoparticles in water. Thus, in many cases, water-dispersibility and biocompatibility of nanoparticles is the key to successful biomedical applications. Firstly, a new and simple synthetic method is presented to render hydrophobic metal oxide nanoparticles water-dispersible. Poly(ethylene glycol)–derivatized phosphine oxide (PO-PEGs) ligands were synthesized as water-dispersing ligands through a simple reaction. The ligand exchange process is a very simple reaction between hydrophobic metal oxide nanoparticles and PO-PEG ligands. The resulting nanoparticles were successfully dispersed in aqueous media. Furthermore, PO-PEG ligands could be readily endowed with functional groups through a simple reaction with some bifunctional reagents thereby allowing conjugation of metal oxide nanoparticles with biomarkers possible. PO-PEG stabilized MnO and Fe3O4 nanoparticles were demonstrated to possess T1 and T2 contrasting effect, respectively. The overall synthetic process was relatively simple and inexpensive, and was readily applicable to the large-scale production of water-dispersible and biocompatible oxide nanoparticles for various biomedical applications.Biocompatible manganese oxide nanoparticles were proposed to be a new contrast agent for effective T1 weighted MRI of body organs. These nanoparticles showed enhanced T1 contrasts for imaging in the brains of mice with anatomic cellular distribution within a long imaging time window. Moreover, manganese oxide nanoparticles could be functionalized with targeting agents, and were applied to tumor specific and targeted imaging successfully. Functionalized nanoparticles are therefore predicted to be particularly useful for applications in molecular and cellular MRI, in which the appreciable benefits of T1 contrast agent are preferred over T2 contrasting agents due to particular drawbacks of the T2 contrasting iron oxide nanoparticles. Manganese oxide nanoparticles showed easy delivery, clearance from the body organs and tissues, and tolerable cellular toxicity, and therefore presents huge potential to be developed as an agent for future human clinical applications as well.
FF12: Poster Session: Synthesis of Nanoparticles for Biomedical Applications
Session Chairs
Sangeeta Bhatia
Anja Boisen
Larry Nagahara
Thomas Thundat
Friday AM, December 05, 2008
Exhibition Hall D (Hynes)
9:00 PM - FF12.1
Templated Synthesis of Doped ZnSe Quantum Dots and Functionalization for Biological Tagging Applications.
Tracy Heckler 1 , Qi (Grace) Qiu 1 , Jun Wang 1 , T Mountziaris 1
1 Chemical Engineering, University of Massachusetts, Amherst, Massachusetts, United States
Show AbstractThe doping of II-VI Quantum Dots (QDs) with transition metals is attracting significant attention because of the possibility of tuning their emission wavelength to longer wavelengths than the corresponding bulk gap emission and for the development of magneto-optical QDs for spintronic applications [S. C. Erwin, et al., Nature 436, 91 (2005)]. In this presentation we will discuss the synthesis of ZnSe:Mn and ZnSe:Cu QDs using a microemulsion template, their extraction from the template, surface modification, and stabilization in water for biological tagging applications. The synthesis route is based on a templated growth technique developed in our group [Karanikolos, et al., Langmuir 20, 550 (2004); Nanotechnology 16, 2372 (2005); Nanotechnology 17, 3121 (2006)]. The template consists of a microemulsion having p-xylene as the continuous phase, water as the dispersed phase, and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer as the surfactant. This template is very stable and has very slow droplet-droplet coalescence kinetics, thus eliminating particle aggregation and allowing precise control of particle size. The precursors for Zn, Mn, and Cu were acetates that were dissolved in the aqueous dispersed phase. The concentration of Zn-acetate in the dispersed phase determines the final size of the QDs and the concentration of Mn- or Cu-acetate determines the final dopant concentration in the nanocrystal. The Se precursor was hydrogen selenide gas diluted in hydrogen and was bubbled through the microemulsion. The particle formation process is initiated by an irreversible reaction between hydrogen selenide and the metal-acetates. Coalescence of nuclei leads to the formation of one QD per droplet of the dispersed phase.The fluorescence spectra of the resulting doped ZnSe QDs exhibit a blue-violet peak attributed to ZnSe gap emission and either a yellow-orange peak or a green peak attributed to Mn2+ or Cu2+, respectively. The evolution of the intensity and ratio of the ZnSe:Mn peak was studied as a function of dopant concentration in the precursor solution and time. The results indicate that ZnSe QDs are formed first and Mn2+ slowly diffuses into the ZnSe. To make the doped ZnSe QDs useful as multi-color tags for biological imaging and sensing applications, a procedure was developed that allows QD removal from the microemulsion template, capping with functional hydrophilic ligands, and stabilization in an aqueous solution. The microemulsion-based synthesis technique is easy to scale up and employs less expensive chemicals compared to the common QD synthesis technique that involves injection of organometallic precursors in a hot coordinating solvent.
9:00 PM - FF12.10
Synthesis of Thermal Responsive Biocompatible Amphiphilic Block Copolymers Poly(Oligo(Ethylene Glycol) Methacrylate)-Block-poly(L-amino Acid) for Nanoparticle Self-Assembly.
Amanda Engler 1 , Paula Hammond 1
1 Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Show AbstractNovel amphiphilic block copolymers consisting of a thermal responsive block and a polypeptide block have been designed and synthesized. A unique synthesis scheme has been developed which allows for either block of the copolymer to be used as a macroinitiator for the second block. Atom transfer radical polymerization has been used to make a hydrophilic block consisting of tunable thermosensitive oligo(ethylene glycol) methacrylates that will cloud when solution temperatures are increased. The quasi living polymerization of amino acid-N-carboxyanhydrides has been used to make the hydrophilic block consisting of either poly(benzyl-L glutamate) or poly(carbobenzyloxy-L-lysine). The outer block of these molecules can be functionalized with biospecific ligands. Initial cloud point studies have been performed on the thermoresponsive block using UV-Vis. These molecules have a wide variety of applications including thermal targeted drug delivery, pollutant preconcentration for water purification, and protein purification.
9:00 PM - FF12.12
Size Control and Large-Scale Synthesis of Monodisperse Amine-protected Palladium Nanoparticles.
Ryota Sato 1 , Masayuki Kanehara 1 , Toshiharu Teranishi 1
1 Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
Show AbstractChemically-synthesized palladium nanoparticles (Pd NPs), which consist of Pd core and organic ligand shell, are expected to be applied to functional materials such as heterogeneous catalysts and hydrogen storage materials.[1,2] Moreover, much attention has been paid to the Pd NPs as structural units for the formation of isotropic or anisotropic phase-segregated nanostructures.[3] From the viewpoint of an application to the functional materials, the Pd NPs should fulfill the following requirements: 1) development of the facile synthetic procedure with uniform and tunable size; and 2) the use of the organic ligands which do not react with metallic Pd. Monodisperse and/or size-tunable Pd NPs stabilized by alkanethiol or alkyl phosphine have been recently reported,[4,5] although there is a strong possibility that the elements, S and P, from organic ligands contaminate the Pd cores. Here, we report the size control and large-scale synthesis of monodisperse amine-protected Pd NPs.In a typical synthesis, monodisperse Pd NPs were synthesized by the injection of 1.5 mmol of tetrabutylammonium borohydride (TBAB) dissolved in chloroform (2 mL) into the reaction solution including 0.5 mmol of palladium acetate (Pd(OAc)2), 10 mmol of oleylamine (OAm), and 10 mmol of oleic acid (OAc) at 50 °C under air.[6] Purified particles were readily redispersed in hexane, chloroform, and other non-polar solvents. Resulting particles have the size of 3.0 nm with quite narrow distribution (σ = 0.2 nm). 1H NMR analysis revealed that the Pd NPs were protected by amine ligands.The size of Pd NPs could be controlled from 2 to 5 nm by modifying of the experimental condition. Both an amount of TBAB more than 5.0 mmol and the reaction temperature of ca. 0 °C were required to synthesize of ca. 2 nm Pd NPs. The larger particles could be synthesized by the homoepitaxial growth method.In a large-scale synthesis, we could obtain 423 mg of powdery monodisperse Pd NPs without changing the size and dispersity. The yield of Pd NPs was calculated from the result of TG-DTA to be 93.1 %.REFERENCES[1] H. Kobayashi, M. Yamauchi, H. Kitagawa, Y. Kubota, K. Kato, M. Takata, J. Am. Chem. Soc. 2008, 130, 1828.[2] P. Lu, T. Teranishi, K. Asakura, M. Miyake, N. Toshima, J. Phys. Chem. B 1999, 103, 9673.[3] T. Teranishi, A. Wachi, M. Kanehara, T. Shoji, N. Sakuma, M. Nakaya, J. Am. Chem. Soc. 2008, 130, 4210.[4] N. Zheng, J. Fan, G. D. Stucky, J. Am. Chem. Soc. 2006, 128, 6550.[5] S. -W. Kim, J. Park, Y. Jang, Y. Chung, S. Hwang, T. Hyeon, Y. W. Kim, Nano Lett. 2003, 3, 1289.[6] R. Sato, M. Kanehara, T. Teranishi, manuscript in preparation.
9:00 PM - FF12.13
Upconversion Nanocrystals in Aqueous Colloidal Solution for In-Vivo Imaging.
Anja Hischemoeller 1 , Jörg Nordmann 2 , Klaus Mummenhoff 2 , Markus Haase 1
1 Institute of Chemistry, Inorganic Chemistry I - Materials Science, University of Osnabrueck, Osnabrueck Germany, 2 Department of Biology, Specific Botany, University of Osnabrueck, Osnabrueck Germany
Show AbstractThe synthesis and the characterization of upconverting lanthanide-doped NaYF4 nanocrystals obtain increasing attention due to their promising applications in the field of biolabeling.The NIR-to-visible upconversion process in NaYF4:Yb, Er nanocrystals generates visible light by continuous wave (cw) NIR excitation at low excitation densities. Since any autofluorescence generated by the NIR light will be emitted in the NIR or IR region, biological materials show a very low autofluorescence background under these excitation conditions. In-vivo applications require well separated nanocrystals which are soluble in water. A high colloidal solubility in water was achieved by modifying the particle surface with different agents, e.g. 1-Hydroxyethane-1,1-diphosphonic acid. These surface modifications also increase the upconversion efficiency of the nanocrystals in aqueous solution. As an example for in-vivo imaging with upconverting nanocrystals we show the uptake of lanthanide-doped NaYF4 nanocrystals in aqueous colloidal solution by the roots of plants. Surprisingly, the nanoparticles are able to pass through the cell barriers in the roots and are transported via the flower stalk to the leaves. The luminescence of the particles inside the plant is easily excited with a NIR laser diode and their characteristic Er3+ luminescence spectrum is recorded with a standard fluorescence spectrometer. Microscope images displaying the first stages of particle uptake by the roots have been recorded with a confocal laser scan microscope equipped with a NIR excitation source.
9:00 PM - FF12.14
Synthesis of Au-magnetic Nano-composite and Application for Protein Separation Thereof.
Zhihui Ban 1 , Jason Tubbs 1 , Todd Krauss 1
1 Chemistry, University of Rochester, Rochester, New York, United States
Show Abstract9:00 PM - FF12.15
Luminescent Silver Nanostructures for Biological Imaging.
Jie Zheng 1 2 3 , Yong Ding 4 , Bozhi Tian 2 , Zhong Lin (ZL) Wang 4 , Xiaowei Zhuang 2 3
1 Chemistry, University of Texas at Dallas, Richardson, Texas, United States, 2 , Howard Hughes Medical Institute, Cambridge, Massachusetts, United States, 3 Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States, 4 Material Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
Show Abstract9:00 PM - FF12.16
Nanocrystalline Diamond Coatings: Creation of Proper Surface Topography for Orthopedic Applications.
Lei Yang 1 , Thomas Webster 1 2 , Brian Sheldon 1
1 Engineering, Brown University, Providence, Rhode Island, United States, 2 Orthopedics, Brown University, Providence, Rhode Island, United States
Show AbstractThe idea of using nanocrystalline diamond (NCD) as a coating on orthopedic implants originates back to the last century since NCD possesses superior mechanical and tribological properties as well as chemical stability. However, it is only within recent years that the interactions between NCD and osteoblasts (OB, bone forming cells) have been investigated. In this study, the impact of NCD surface topography on OB functions including adhesion (up to 4 hrs), proliferation (1 to 5 days) and differentiation (7 to 28 days) was studied. NCD of varied grain sizes (from less than 100 nm to approximately 800 nm) were fabricated by microwave plasma enhanced chemical-vapor-deposition and characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Surface topography of the NCD changed dramatically as grain size grew. These coatings were tested for OB adhesion and proliferation after incubation for 4 hrs and up to 5 days, respectively. OB differentiation on diamond coatings after incubation from 1 to 4 weeks was investigated by measuring protein synthesis, collagen synthesis, alkaline phosphatase activity, and calcium deposition. Results demonstrated that OB functions were dependent on topography with NCD grain sizes less than 100 nm exhibiting the best OB functions. SEM observations of OB proliferation on NCD of varied topographies also confirmed a higher cell number and better cellular spreading on the samples with grain sizes less than 100 nm. To explain this enhancement, OB filopodia protrusions on different NCD were compared and a mechanical model of filopodia responding to different surface morphologies was constructed. Cell and modeling results revealed that surface topography of NCD played a crucial role in governing OB responses and functions. In summary, these findings provide important design criteria for creating proper NCD surfaces for orthopedic coatings and also provide cues on promoting interactions between nanostructured surfaces and cell responses.
9:00 PM - FF12.17
Fabrication of MnXFe1-XO Solid Solution as a Dual MR Contrast Agents.
Sang-Wook Kim 1 , Donghyeuk Choi 1 , Anna Han 1 , Joong Pill Park 1
1 Molecular Science & Technology, Ajou University, Suwon Korea (the Republic of)
Show Abstracthomogeneous MnxFe1-xO solid solution nanocrystals were fabricated. The nanocrystals exhibited interesting stability despite having a metastable wüstite structure, which resulted from the structural difference in the oxidized forms of Fe3O4 (spinel) and Mn3O4 (tetragonal), respectively. They also exhibited simultaneous T1 and T2 contrast enhanced effects in a specific composition, which might result from different magnetic moments of the constituent Mn2+ and Fe2+.
9:00 PM - FF12.18
B2↔A2 Order-Disorder Transition and Core-to-Surface Atomic Evolutions in Near Equiatomic FeCo and FeCo-Au Nano-Spheres and Nano-Cubes for Biomedical Applications.
Muratahan Aykol 1 , Amdulla Mekhrabov 1 , M. Vedat Akdeniz 1
1 Metallurgical and Materials Engineering, Middle East Technical University, Ankara Turkey
Show AbstractMultifunctional FeCo nanoparticles with high magnetic moment have potential use in biomedical applications such as drug delivery, hyperthermia and magnetic resonance imaging. With the recent progress in direct synthesis of FeCo and FeCo-Au nanoparticles with narrow size distributions and controllable shapes, a demand of investigation on degree of retained long range order (LRO) in these magnetic nanoparticles arose since a great many physico-chemical and magnetic properties are dependent on the nature of order disorder transition (ODT). The shape of the particles may alter ODT and related magnetic properties due to confined atomic structure yielding anisotropic crystallographic arrangements and high energy disordering surface defects like edges or facets.In this study, we employed first-principle pseudopotential theory combined with Monte Carlo (MC) simulation method to reveal the response of degree of order to varying particle size (2.0-5.0 nm) and shape (spherical and cubic) below the superparamagnetic limit in near equiatomic B2-FeCo nanoparticles from room temperature to higher temperatures. It is found that particles over 5 nm size show no practical difference from bulk FeCo’s LRO response to varying temperature. Although it is impossible to fully equilibrate the systems of limited number of atoms, LRO parameter fluctuations attained during MC simulations were minimal enough to extract surface-to-core order profiles in FeCo and FeCo-Au alloys with 2.0-5.0 nm sized nanoparticles and bulk forms. Particles of any size and shape with free boundaries show lower degree of LRO and diffuse ODT with varying temperature, in contrast to the well defined ODT temperature of ~1000 K of bulk FeCo, the effect becoming more pronounced with decreasing particle size. In FeCo-Au alloys, Au atoms embedded into nanoparticles show tendencies to segregate to particle surfaces which might be useful during direct synthesis of FeCo-core/Au-shell type particles for biocompatibility and organic molecule attachments. Alloying with Au retards B2↔A2 ODT to lower temperatures both in bulk and nanoparticle forms, the latter bearing more disorder due surface-initiated disordering effect.
9:00 PM - FF12.19
A Facile, `Green' One – Step, Room Temperature Synthesis of a Series of monodispersed MSe(M = Cd or Zn) Water Dispersible Nanoparticles.
Oluwatobi Oluwafemi 1 , Neerish Revaprasadu 1
1 Chemistry, University of Zululand, Kwadlangezwa, Kwa-zulunatal, South Africa
Show AbstractThe conjugation of semiconductor nanoparticles with biomolecules such as carbohydrates, proteins, vitamins and nucleic acids through biosynthesis and biological surface modification, have added a new dimension to nanoparticles research. Though many methods for preparing these highly functionalised materials have been reported, the search for a greener sustainable method involving less toxic starting materials, smaller waste products and room temperature synthesis is still ongoing. We herein report a facile, ‘green’ one- step synthesis of a series of monodispersed water soluble CdSe and ZnSe nanoparticles at room temperature. The capping ligands used include: cysteine, methionine, ascorbic acid and starch which function as agents of solubilisation, stabilization and conjugation with biomolecules. The synthetic approach involves addition of appropriate volume of selenide ion produced via reduction of selenium powder in water to an aqueous solution containing the ligand- metal salt (MCl2 M = Zn or Cd) without additional stabilizing agent. The temporal evolution of the optical properties of the growing nanocrystals was monitored in detail by varying the pH, growth time and concentration. The effect of these parameters on size, shape and optical properties will be discussed. The structural properties of the particles were investigated using x- ray diffraction, transmission electron spectroscopy (TEM), and IR spectroscopy. The TEM of the samples show variation in shapes ranging from dots, rods, and mixture of mono-rods to multi-armed rods of high and low aspect ratio depending on the varied parameters. The insight gained from this green synthetic approach will enable an economically viable and environmentally benign method for the synthesis of functionalised water soluble nanoparticles for large scale production and commercialisation.
9:00 PM - FF12.2
Titanium Dioxide Nanostructures Fabricated by Atomic Layer Deposition using Spherical Protein Cages.
Hyunbin Kim 1 , Eckhard Pippel 1 , Joerg Woltersdorf 1 , Wilfried Erfurth 1 , Ulrich Goesele 1 , Mato Knez 1
1 , Max Planck Institute of Microstructure Physics, Halle Germany
Show AbstractTitanium dioxide (TiO2) is known to be highly biocompatible and stable in biological environment. TiO2 can be used in biosensor applications because it reveals superior bioaffinity to accumulate the dissolved molecules on its surface. Particularly nanostructured TiO2 surface might provide more effective interaction area and more feasible electron transfer interfaces. In addition, TiO2 layer on dental or orthopedic Ti implant has been reported to increase corrosion resistance and enhance biocompatibility of implant. Nanostructured surface of Ti implant is reported to increase initial attachment, proliferation, and spreading of the cells, which can determine the long-term viability of cells on substrate. TiO2 can also serve as delivery scaffolds for drugs and imaging agents. In order to produce nanostructured TiO2 surface, we have employed spherically shaped protein cages such as apoferritins as templates. Biological templates have been recently paid attention to for fabrication of inorganic materials at the nanoscale because they are fairly robust and easily removable. Among various biological molecules with different geometries and structures, apoferritins have been of special interest as templates for nanofabrication because they are easy to handle, stable up to 85 °C and simple in structure. Apoferritin is primarily an iron-storage protein found in the living organisms. It is mainly composed of 24 peptide subunits that self-assemble to form a sphere-like cage of 12−14 nm in diameter with a central cavity of 6−8 nm in diameter. In this study, we demonstrate the capability of spherically shaped protein cages, i.e. apoferritins, as templates for controlled synthesis of TiO2 nanostructures by atomic layer deposition (ALD). We also show how to manipulate the TiO2 nanostructures with a constrained size using apoferritin molecules. The surface microstructure was mainly investigated by high resolution transmission electron microscopy (TEM) and the chemical composition was determined by energy dispersive X-ray analysis (EDX) and electron energy loss spectroscopy (EELS) during TEM investigation. We identified fabrication of TiO2 hollow spherical nanoshells (inner diameter: 12−14 nm, outer diameter ≥ 15 nm) and TiO2 nanoparticles (5−7 nm in diameter) by gas-phase reactions in the ALD process assisted by apoferritin molecules. Our results suggest that supramolecular protein cages such as apoferritins have the potential to provide a promising platform for nanoscale surface engineering that is highly desirable in various biomedical applications.ACKNOWLEDGEMENTS: This research was supported by the German Federal Ministry of Education and Research (BMBF) under Grant No. FKZ 03X5507. The authors thank Mr. Norbert Schammelt for his assistance with TEM sample preparation using Focused Ion Beam (FIB) system.
9:00 PM - FF12.20
Supercritical Fluid Assisted One-pot Synthesis of Biocompatible Core(γ-Fe2O3)@shell(SiO2) Magnetic Nanoparticles.
Elena Taboada 1 , Anna Roig 1 , Raul Solanas 2
1 Crystallography Dpt., Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Bellaterra Spain, 2 , MATGAS AIE, Bellaterra Spain
Show AbstractThe specific materials design to generate useful agents for biomedical applications such as magnetic resonance imaging (MRI), biological targeting or separation, drug delivery, tissue repair, etc., is a key point to improve the performance of all these medical tools.The materials design has to be directed towards the fabrication of biocompatible, multifunctional, and, if possible, therapeutic and diagnostic materials at the same time, to improve the patient’s treatment quality.We have focussed our attention on the synthesis of magnetic materials for their first use as contrast agents for MRI, complemented with a porous structure to be potentially used for drug delivery or further functionalized with targeting directing agents, fluorescent complexes, etc.The synthesis of core(γ-Fe2O3)@shell(porous silica) nanoparticles (NPs) is done in a straight forward one-pot method, which we believe has the potentiality of being scalable to produce large quantities of material. Briefly, previously synthesized iron oxide superparamagnetic NPs, 7 nm in diameter, are dispersed in a sol containing a silicon precursor, water and acetone as the solvent. The sol is introduced in a supercritical reactor which is pressurized with compressed CO2. Then, pressure and temperature are raised over the supercritical conditions of the CO2/acetone mixture, allowing the silicon precursor to hydrolyze and condensate forming silica gel NPs. The composite nanoparticles are dried as the system is depressurized and the solvent is extracted in the supercritical phase, thus, avoiding the capillary pressure in the gel pores, i.e. the collapse of the pore structure.Advantages of the method are its short reaction time, compared to non-supercritical sol-gel procedures, and purity of the product, since the final material is a dry powder, free of unreacted precursors and organic solvents. Additionally, dry powder is easier to store and manipulate than colloidal dispersions.The composite NPs are formed by a magnetic core of several non-contacting γ-Fe2O3 NPs, surrounded by a microporous silica shell. The composite size can be tuned from 50 to 200 nm by controlling the reactants ratio and the reaction conditions (P, T and depressurization procedure). They are superparamagnetic at RT, with an enhanced magnetization compared to the initial iron oxide NPs. The silica shell avoids the aggregation of the particles, ensuring their magnetic stability. Their efficiency as contrast agents for MRI has been evaluated. Silica coating was also chosen for its biocompatibility; toxicity tests have been performed.To sum up, we will present a novel one-pot sol-gel method assisted by supercritical facilities to synthesise a complex structure formed by a superparamagnetic core(γ-Fe2O3) and a shell(microporous silica). The synthesis and relevant properties for their use in life sciences will be described.
9:00 PM - FF12.21
CeO2 Nanostructure Thin Film Grown by PLD for Biosensor Application.
Shibu Saha 1 , Sunil Arya 2 , S. Singh 2 , K. Sreenivas 1 , B. Malhotra 2 , Vinay Gupta 1
1 Department of Physics & Astrophysics, University of Delhi, Delhi, Delhi, India, 2 BECPRG, National Physical Laboratory, Delhi, Delhi, India
Show AbstractMetal oxide semiconductors are very promising materials exhibiting multifunctional properties. In this context, nano-structures are receiving great deal of attention because of their novel optical and electrical properties compared to their bulk counterpart, arising from the confinement of electrons and phonons. Owing to their high ionic conductivity, capacitive action, catalytic properties and high isoelectric point (IEP) the semiconducting metal oxides have also gained considerable interest in the fields of biosensors as an alternate matrix. Cerium oxide (CeO2) having high IEP (~ 9.0), excellent electronic conductivity and ability to act as redox couple could provide an attractive matrix for a mediator-less amperometric biosensor application. CeO2 has found extensive applications, such as electrolytes for solid oxide fuel cells, ultraviolet absorbents, oxygen sensors, solar cells and as catalyst. In the present study CeO2 nanostructured films were grown by pulsed laser deposition on Platinum coated glass. The matrix was immobilized with glucose oxidase enzyme. AFM, FTIR and Impedance Spectroscopy confirms successful immobilization of the enzyme on the matrix. The prepared bio-electrode (Glass/Pt/CeO2/GOx) could be used as an amperometric bio-sensor without any external mediator in Phosphate Buffer Saline (PBS) Solution (7.0 pH). An oxidation peak was observed at 0.33 V in DPV spectra and the oxidation current was found to increase continuously with an increase in glucose concentration over the range 50-300 mg/dl. The observed results show promising application of CeO2 thin films for biosensors without any functionalization.
9:00 PM - FF12.23
Formation and Color of Gold Nanorod-Based Nanostructures.
Jianfang Wang 1
1 Physics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR China
Show AbstractI will present our recent work on the preparation, characterization, and assembly of gold nanorod-based nanostructures. Such noble metal nanostructures exhibit rich shape- and size-dependent plasmonic properties, and therefore they have enormous potential for a wide range of technological applications. Specifically, we have developed methods to grow gold nanorods and nanobipyramids with controlled lengths and diameters. Such control allows for tailoring the scattering and absorption cross sections of gold nanorods for scattering-based imaging and absorption-based photothermal therapy applications. We have demonstrated the assembly of gold nanorods in either end-to-end or side-by-side fashions. The assembly and disassembly can be reversibly controlled. Finite-difference time-domain calculations have been carried out to help in understanding the plasmonic properties of individual and assembled gold nanorod-based nanostructures. The sensing capability of these gold nanostructures has been investigated by attaching them to optical fibers, where the evanescent wave of optical fibers is used to excite the surface plasmon resonance of gold nanostructures. The index sensitivities of gold nanostructures of varying shapes and sizes have been systematically studies. We have further investigated the coupling behavior between the molecular and plasmonic resonances by constructing the dye-gold nanorod hybrid nanostructures. The anticrossing between the two resonances has been observed. We believe that the resonance coupling offers a new platform for designing ultrasensitive sensing and photoswitching devices.Related publications from our group:[1] J. Am. Chem. Soc. 2006, 128, 5352.[2] J. Phys. Chem. B 2006, 110, 16377.[3] Chem. Commun. 2007, 1816.[4] Chem. Eur. J. 2007, 13, 2929.[5] Small 2007, 3, 2103.[6] J. Am. Chem. Soc. 2007, 129, 6402.[7] ACS Nano 2008, 2, 677.[8] J. Am. Chem. Soc. 2008, 130, 6692.[9] Langmuir 2008, 24, 5233.[10] J. Phys. Chem. C 2008, 112, 8105.
9:00 PM - FF12.3
Diamond-like Carbon Film Coating for Tissue Engineering.
Yasuharu Ohgoe 1 , Kazuya Kanasugi 1 , Toshiyuki Yaguchi 1 , Kazuhiro Nonaka 1 , Haruki Matsuo 1 , Kenji Hirakuri 2 , Akio Funakubo 1 , Yasuhiro Fukui 1
1 , Tokyo Denki University, Saitama Japan, 2 , Tokyo Denki University, Tokyo Japan
Show Abstract9:00 PM - FF12.4
Tuning the Properties of Gold Nanocages by Controlling the Synthesis of Silver Templates.
Claire Cobley 1 , Jingyi Chen 1 , Younan Xia 1
1 Biomedical Engineering, Washington University in St Louis, St Louis, Missouri, United States
Show AbstractGold nanocages have been shown to be a promising platform for biomedical applications including drug delivery, photothermal therapy, and contrast enhancement in optical imaging techniques such as optical coherence tomography and photoacoustic tomography. These structures are easily produced through a simple and tunable galvanic replacement reaction between silver templates and chloroauric acid and have been synthesized as small as 10-15 nm. The properties of the gold nanocages produced during this reaction depend strongly on the features of the silver template used during the replacement reaction. For this reason, it is important to understand both the effect that template features such as crystal facets, size, and shape have on the final product and how such features can be controlled synthetically. Using a sulfide-mediated polyol synthesis to produce silver templates, we report the results obtained when parameters such as reaction time and surfactant concentration (poly(vinyl pyrrolidone)) are controllably altered to produce different silver templates. We also report the optical and morphological differences observed when these different silver templates are used in a galvanic replacement reaction with chloroauric acid.
9:00 PM - FF12.5
Preparation of Styrenic Block Copolymer through Nitroxide Mediated Polymerization Technique and its Application as Organic Modifier for Poly(bisphenol A diglycidyl ether methacrylate) (Poly(bis-GMA)) / Montmorillonite (MMT) Nanocomposite.
Sang-il Joo 1 , Myung-hwan Oh 2 , Won-ho Kim 2 , Jonghwi Lee 3 , Sung Chul Hong 1
1 Department of Nano Science and Technology, Sejong University, Seoul Korea (the Republic of), 2 , Vericom, Anyang-si Korea (the Republic of), 3 Chemical Engineering and Materials Science, Chung-Ang University, Seoul Korea (the Republic of)
Show AbstractPolymer/clay hybrid nanocomposites have been attractive materials, exhibiting improved mechanical, thermal, and optical properties. In order to achieve enough compatibility of polymer with hydrophilic surfaces of clay, clay platelet surfaces are generally modified with organic modifiers. In this study, we prepared a dual-function block copolymer modifier, which was composed of pendant methacrylate functional group in one block and 4-vinylpyridine repeating unit in the other block. Polymerizable methacrylate unit was introduced to the modifier for potential co-crosslinking with poly(bis-GMA) matrix, while 4-vinylpyridine repeating unit was introduced for cationic exchange reaction with Na+-MMT. Well defined poly(maleic anhydride-co-styrene)-block-poly(styrene-co-4-vinylpyridine) was first prepared through nitroxide mediated polymerization technique, followed by a functionalization of maleic anhydride repeating unit with 2-isocyanatoethylmethacrylate. Na+-MMT was modified through cation exchange reaction employing the block copolymer in the presence of HBr. Poly(bis-GMA)/MMT nanocomposite was then prepared using the modified MMT, and its properties were investigated for dental applications.
9:00 PM - FF12.6
The Implications of Stochastic Synthesis for the Conjugation of Functional Groups to Nanoparticles.
Douglas Mullen 1 2 , Ankur Desai 2 , Jack Waddell 3 , Xue-min Cheng 2 , Christopher Kelly 2 4 , Daniel McNerny 2 5 , Istvan Majoros 2 , James Baker 2 , Leonard Sander 6 , Bradford Orr 2 4 , Mark Banaszak Holl 1 2 7
1 Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan, United States, 2 Michigan Nanotechnology Institute for Medicince and Biological Sciences, University of Michigan, Ann Arbor, Michigan, United States, 3 Department of Mathematics, University of Michigan, Ann Arbor, Michigan, United States, 4 Applied Physics Program, University of Michigan, Ann Arbor, Michigan, United States, 5 Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States, 6 Department of Physics, University of Michigan, Ann Arbor, Michigan, United States, 7 Department of Chemistry, University of Michigan, Ann Arbor, Michigan, United States
Show AbstractA common strategy to produce practical quantities of functionalized nanoparticles is stochastic conjugation of a ligand to a nanoparticle surface. Analytical methods used to quantify the nanoparticle to ligand ratio, such as NMR, UV/vis spectroscopy, and elemental analysis, provide only a mean average ratio. No information about the distribution of ligands bound to each particle that gives rise to the average is obtained. Here, we report the successful resolution and quantification of the distribution using HPLC, and find that it is in excellent agreement with the ligand/nanoparticle average measured by 1H NMR, GPC, and potentiometric titration, yet significantly more disperse than commonly held perceptions of monodispersity. Two statistical models were employed to confirm that the observed heterogeneity is consistent with theoretical expectations. Given the importance of nanoparticle conjugates for applications such as drug delivery, biomedical diagnostics, and sensing, it is paramount that a detailed understanding of the products that result from stochastic synthesis methods be gained.
9:00 PM - FF12.7
Preparation of New Bio-relevant Materials via Surface-initiated Ring-Opening Metathesis Polymerization in the Vapor Phase.
Maria Felisa Lerum 1 , Wei Chen 1
1 Department of Chemistry, Mount Holyoke College, South Hadley, Massachusetts, United States
Show AbstractThe increasing demand for biomaterials such as those utilized for artificial implants and organ and tissue replacements continues to propel research in this area. A foreign object when implanted in the body can elicit a cascade of events that include protein adsorption followed by cell adhesion and various adverse biological responses. Hence, the development of biomaterials whose surfaces are resistant to adsorption and adhesion is critical for such applications. Poly(ethylene glycol) and phosphorylcholine-containing molecules are among the few available and well-studied biocompatible materials. While there are numerous efforts to improve biocompatibility, the design of new materials and an understanding of their non-fouling properties remain to be a challenge.In this report, we have explored surface-initiated ring-opening metathesis polymerization (SiROMP) of cyclic olefins in the vapor phase and subsequent hydroxylation reaction as an efficient approach to tether new materials on silicon substrates. SiROMP has been widely used to covalently attach functionalized linear polymeric chains to substrates, with the reported monomers for solution reactions limited to norbornene and its derivatives. Herein, we demonstrate that the SiROMP in the vapor phase can provide access to polymers of low ring strain cyclic monomers, such as cyclooctadiene (COD). In contrast to solution phase SiROMP, polymerization in the vapor phase offers the advantage of minimizing chain transfer at the solid/vapor interface. A novel material, namely, head-to-head poly(vinyl alcohol) was successfully synthesized after hydroxylation of poly(cyclooctadiene)/polybutadiene. This study is extended to other cyclic olefins with varying degrees of ring strain and unsaturation, including cyclopentene, cycloheptene, cyclooctene and cyclooctatetraene. These unsaturated polymers when hydroxylated can give an array of materials that have different –OH group densities. We would like to correlate the –OH group density along the polymer chain to protein adsorption characteristics and compare them to well-recognized biomaterials. Surface characterizations were carried out using ellipsometry, contact angle goniometry, atomic force microscopy and x-ray photoelectron spectroscopy. Grafted polymer thickness, wettability and protein adsorption properties will be reported. Various reaction parameters such as silanization kinetics, catalyst loading and grafting time and their influences on the molecular weight of the polymers will be discussed.
9:00 PM - FF12.8
Synthesis and Characterization of Magnetic FeCo Coated with SiO2 Nanocomposite.
Kai Zhang 1 , Aswini Pradhan 1
1 , Norfolk State University, Norfolk, Virginia, United States
Show AbstractWe report coprecipitation method to synthesized magnetic FeCo nanoparticles and FeCo encapsulated with a thin SiO2 layer by sol-gel technique. The uniform size distribution was determined by optimum reaction time and the size of the nanoparticles and thickness of SiO2 layers was obtained by field emission scanning electron microscopy (FE-SEM) and Transmission electron microscopy (TEM). X-ray diffraction results indicated the crystallinity of FeCo nanoparticles is dependent on the reaction time. Room temperature hysteresis loops taken on the SQUID magnetometer show FeCo nanoparticles produced by this chemical route have ferromagnetic properties and high saturation magnetization. The composite of FeCo coated with SiO2 nanolayer can be used to cell separation and drug delivery in biomedical technology.
9:00 PM - FF12.9
A Novel Approach to Synthesis and Characterization of Biocompatible ZnO Nanoparticles.
N. Nag 1 , J. Doak 1 , R. Gupta 1 , S. Mishra 2 , P. Kahol 1 , K. Ghosh 1 , K. Manivannan 1
1 Department of Physics, Astronomy, and Materials Science, Missouri State University, Springfield, Missouri, United States, 2 Department of Physics, The University of Memphis, Memphis, Tennessee, United States
Show AbstractZnO nanoparticles being biocompatible and chemically stable have much potential for bio–medical application that includes anti-bacterial and mold prevention, air ventilation and purification, water purification, self cleaning and photosynthesis, and disease detection. Also ZnO is a wide band gap semiconductor and exhibits piezoelectric and pyroelectric properties, which makes it a perfect candidate for building electrochemical coupled sensors and transducers. With all these unique properties ZnO could be the potentially most important nanomaterial in material research area. Therefore, the research, development, and production of ZnO nanoparticles would be a notable contribution to the field of nanotechnology. In this paper we report a novel approach for fabrication of ZnO nanoparticle suspension in deionized water at room temperature using pulsed laser deposition (PLD) technique. Characterization of the nanoparticles has been done using UV-Visible spectroscopy, fluorescence spectroscopy, transmission electron microscopy and dynamic light scattering. UV-VIS study confirmed the existence of ZnO nanoparticles showing a peak at around 300 nm which is consistent with the absorption spectra of standard ZnO nanoparticles. Presence of ZnO was reconfirmed by the excitation and emission spectra obtained from fluorescence spectroscopy. The excitation and emission peaks were found at 305 nm and 410 nm wavelength respectively strongly suggesting the characteristic peaks for ZnO nanoparticle. Transmission electron microscope photographs established the fact that we have successfully prepared ZnO nanoparticle suspension with particle size ranging from 6 nm to 80 nm. Particle size was controlled by the number of shots of the laser beam used. This work is partially supported by Research Corporation (award number CC6166).
9:00 PM - FF12: Synthesis
FF12.11 TRANSFERRED TO FF3.35
Show Abstract