Stefan Maier Imperial College London
Ulrich Wiesner Cornell University
Jinwoo Lee Pohang University of Science and Technology
TT1: Biosensing with Nanostructures and Molecular Signaling
Monday AM, November 30, 2009
9:30 AM - **TT1.1
Molecular Engineering of Bionano Interfaces for Bionanosensors.
Tony Cass 1 Show Abstract
1 Institute of Biomedical Engineering, Imperial College London, London United Kingdom
The design, fabrication and characterisation of interfaces between nanostructured materials and biological molecules presents both opportunities and challenges. The opportunities are in building novel devices with enhanced performance that can exploit the matching of length scales between nano- materials and biomolecules, the challenges lie in ensuring that the proper function of both 'hard' and 'soft' components are preserved.Biomolecules in particular often display only marginal functional stability at room temperature and their structures represent a delicate balance between forces that stabilize the native, functional state and those that favour the potentially many non-functional states. This balance can be tipped by the interactions of the biomolecules with nano-surfaces. One approach to using molecular design in building bio-nano interfaces is to treat the biological component as a set of functional modules and to try and ensure that the surface binding module dominates the interactions with the solid state material.Where the interface forms part of a bionanosensor, additional modules impart a capacity for molecular recognition and signal transduction. A characteristic of such sensors is that the latter often exploits the particular electronic or photonic properties of the underlying nanostructured material and therefore the challenge is not just retention of the biomolecule’s properties but also efficient coupling in signal generation.Amongst biomolecules, both nucleic acids and proteins have the requisite structural and functional properties to form the basis of nanobiosensors and in this presentation I will describe the chemical and genetic tools for building bionano interfaces with these molecules.
10:00 AM - TT1.2
Single-Walled Carbon Nanotube Optical Sensor Technologies.
Daniel Heller 1 , Michael Strano 1 Show Abstract
1 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Single-walled carbon nanotubes (SWNT) offer the potential for photostable, quantitative optical bioanalyte detection with single-molecule sensitivity and analyte identification in real-time from within absorptive biological media. We demonstrate several SWNT optical sensor systems which exhibit the potential for this technology. Semiconducting SWNT emit photostable, near-infrared photoluminescence which is ultrasensitive to molecular adsorption and takes advantage of the ‘tissue transparent’ spectral window. Transduction involves several modalities including charge transfer-induced quenching as well as solvatochromic shifts. Nanotubes thus produce differentiable optical responses depending on the adsorbate. To transduce analyte-binding events into a photoluminescence signal, we design SWNT-polymer complexes to undergo chemical or conformational changes to the coating, which induce quenching, signal amplification, or solvatochromic shifts up to 50 meV. We have fabricated sensors for detection of glucose, mercury ions, two classes of chemotherapeutic drugs, and several reactive oxygen species (ROS). Optical SWNT sensors have the potential to detect analytes down to the single-molecule level due to the nanotube’s ultrasensitivity to adsorption events. We have developed a sensor platform for single-molecule hydrogen peroxide detection which detects stochastic binding events. Each semiconducting SWNT species possesses unique electronic characteristics, providing multiple sensors with distinctive responses. By fabricating sensors using several SWNT species, one can use spectral information to identify specific analytes. We conducted multiplexed detection via spectroscopic analysis, resulting in identification of analytes which are traditionally difficult to differentiate, including singlet oxygen, hydrogen peroxide, and hydroxyl radicals. We present photoluminscent carbon nanotube biosensors as label-free tools which offer single-molecule sensitivity, near-infrared spectral advantages, real-time detection capabilities, and optical discrimination between analytes.
10:15 AM - TT1.3
Colorimetric Signature Biosensing with Photonic-plasmonic Surfaces.
Yuk Kwan Sylvanus Lee 1 , Jason Amsden 4 , Svetlana Boriskina 2 , Ashwin Gopinath 2 , Bjorn Reinhard 3 , Fiorenzo Omenetto 4 , Luca Dal Negro 2 Show Abstract
1 Mechanical Engineering, Boston University, Boston, Massachusetts, United States, 4 Biomedical Engineering, Tufts University, Medford, Massachusetts, United States, 2 Electrical and Computer Engineering, Boston University, Boston, Massachusetts, United States, 3 Chemistry, Boston University, Boston, Massachusetts, United States
In this work, we investigate optical sensing by spectral color localization in photonic-plasmonic nanostructured surfaces consisting of gold nanoparticles and air holes (200nm diameter) arrays on quartz substrates. Arrays with minimum interparticle separations ranging from 50nm to 200nm were fabricated using electron beam lithography and nanoimprinting pattern transfer fabrication techniques. Bovine serum albumin (BSA) protein films with different concentrations were deposited on the arrays and their scattering spectra were experimentally measured by dark-field spectroscopy under white light illumination. Spectrally resolved correlation analysis was performed on the colorimetric signature (color localization patterns) which form in aperiodic arrays, and compared with rigorous multiple scattering semi-analytical calculations based on the Generalized Mie Theory. Using BSA protein monolayers as our biological target, we designed, fabricated and optimized different aperiodic structures, which provide broadband electric field enhancement and mode localization for enhanced biological sensing. Our results demonstrate for the first time that the characteristic color localization patterns observed in lithographically defined aperiodic photonic-plasmonic structures can be directly utilized as highly sensitive colorimetric signatures for protein detection and optical biosensing applications.
10:30 AM - **TT1.4
Design Principles of Mechano-Chemical Signal Converters.
Viola Vogel 1 Show Abstract
1 , ETH Zurich, Zurich Switzerland
How do cells sense the properties of materials that surround them? While mounting evidence exists that cells and tissues sense mechanical stimuli and convert them into biochemical signals, the underpinning mechanisms remain unclear. Optical mechanical strain probes have been incorporated into extracellular matrix fibers to probe that cells utilize mechanical force to switch protein function. New nanotechnology and computational tools begin to reveal that a multitude of structural mechanisms seem to have evolved enabling mechano-chemical signal conversion. The structural motives include designs by which force can destroy recognitions sites, or alternatively open up cryptic sites that can then recruit other proteins in a force-upregulated manner. Deciphering the underlying engineering design principles by which proteins can serve as mechano-chemical signalling switches is not only essential to learn how cells sense and respond to mechanical forces. It has far reaching implications in tissue engineering, systems biology and medicine. Illustrative examples will be discussed.
TT2: Applied Bionanosystems I
Monday AM, November 30, 2009
11:30 AM - TT2.1
Nanowire Transistor Arrays for Subcellular-Scale Nanoelectronic – Cell Interfaces.
Tzahi Cohen-Karni 1 , Lucien Weiss 2 , SungWoo Nam 2 , Quan Qing 2 , Charles Lieber 1 2 Show Abstract
1 School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States, 2 Chemistry and Chemical Biology, Harvard University, Cambridge , Massachusetts, United States
Semiconductor nanowires are emerging as unique nanostructures for establishing active interfaces with biological systems due to their relevant size and controllable electronic and surface properties. Here we report subcellular scale nanoelectronic interfaces with cells using silicon nanowire field-effect transistor (Si-NWFET) arrays that exceed the spatial and temporal resolution limits of other reported cellular electrical recording techniques. Embryonic chicken cardiomyocyte cells were cultured on thin, optically-transparent polydimethylsiloxane (PDMS) sheets and then brought into contact with high density Si-NWFET arrays fabricated on standard substrates. This flexible scheme allows us to manipulate the interfaced cells while monitoring their electrical activity at the subcellular regime. The assembly and interfacing of high density arrays of Si-NWFETs opens up fundamental studies of ion channel biophysics, real-time drug assays and creation of semiconductor/muscle hybrids.
11:45 AM - TT2.2
Soft Nanomembranes for Interfacing Inorganic Semiconductors with Biological Cells.
Francesca Cavallo 2 , David Grierson 1 , Max Lagally 2 , Kevin Turner 1 2 Show Abstract
2 Materials Science and Engineering, University of Wisconsin-Madison, Madison, Wisconsin, United States, 1 Mechanical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, United States
Cells are able to sense and actively respond to their mechanical environment, thus integrating engineered devices in biological environments requires careful consideration of the compliance of materials at the interface between the devices and cells. It is well known that the compliance of the cellular environment can affect the adhesive interactions, the internal cytoskeletal structure, the migration behavior, and the overall state of the cell. The elastic modulus of a typical natural cellular environment is on the order 10-100 kPa, while common metals and inorganic semiconductors have elastic moduli in the range of 10-200 GPa. This large difference in elastic modulus makes it a significant challenge to integrate semiconductor and photonic devices with biological cells without altering the cell state. We examine routes to match the stiffness of inorganic semiconductors to that of the cellular environment by introducing compliance through geometry rather than material choice. Specifically, we exploit the exceptional compliance of large-area (~1000-10000 µm2), thin (5-100 nm), single-crystal silicon nanomembranes to create inorganic devices with stiffnesses that match natural cellular environments. The stiffness of a surface depends on the elastic modulus as well as the geometry of the surface. By moving from bulk semiconductors to thin sheets with large width to thickness ratios, the effective compliance of Si nanomembranes can be reduced to match that of bulk soft materials. We have used a combination of analytical and finite-element mechanics models to explore the geometric space in which this stiffness matching can be achieved. Predictions of both and normal and shear stiffness as a function of contact size for different membrane structures will be reported and discussed. A key result is that the membrane geometry not only affects the overall stiffness, but also determines the relative magnitudes of the shear and normal stiffness. Furthermore, the relevance of shear and normal stiffness to interactions with cells will be discussed. The modeling is supported by experimental results that demonstrate the fabrication and feasibility of the Si nanomembrane geometries considered as well as AFM indentation measurements of the local stiffness of membrane structures.This work is supported by AFOSR (#FA9550-08-1-0337), NSF MRSEC (DMR-0520527), and the U.S. Department of Energy, Office of Basic Energy Sciences (DE-FG02-03ER46028).
12:00 PM - TT2.3
Self-Assembled Nanostructured Materials for Energy Conversion and Sensor Application.
Jongmin Shim 1 , Youngjin Ye 1 , Moon-Il Kim 2 , Hyun Kyu Park 2 , Ulrich Wiesner 3 , Sangmin Jeon 1 , Jinwoo Lee 1 Show Abstract
1 Chemical Engineering, POSTECH, Pohang Korea (the Republic of), 2 Chemical Engieering, KAIST, Daejon Korea (the Republic of), 3 Materials Science and Engineering, Cornell University, Ithaca, New York, United States
Self-assembled nanostructured materials have attracted much attention owing to their application to catalyst supports, hosts for biomolcules, and sensors. The first synthesis of ordered mesoporous materials stimulated research on the self-assembly of block copolymers with inorganic materials. Herein, we present functional nanostructured materials synthesized by the self-assembly of block copolymers with inorganic materials. Highly crystalline mesoporous transition metal oxides were fabricated through ‘one-pot’ assembly method employing PI-b-PEO block copolymers. We developed intermetallic nanoparticle loaded highly ordered mesoporous carbon and transition metal oxides by the assembly of PI-b-PEO block copolymer. Formic acid oxidation with the resulting catalyst shows higher mass activity and lower onset potential compared with commercial Pt based catalyst. Highly crystalline mesoporous TiO2 was employed as self-cleaning sensors with higher sensitivity compared with commercial TiO2 pastes. Large cellular porous silica materials were synthesized by the self-assembly of commercially available block copolymers, P123. One-pot multi-catalyst system, so called “nanofactory”, was developed entrapping magnetic nanoparticles and oxidases in large cellular mesoporous silica with high loadings of simultaneously above 40 wt% MNPs and 20 wt% enzymes. Our approach provided highly loaded MNP system and any highly loaded enzymes with superior activity, stability, and reusability, thereby making further applications as versatile sensors for detecting DNA, protein, and cell highly promising.
12:15 PM - TT2.4
An Alumina Nanopore-based Label-free Nucleic Acid Fingerprinting Microarray Sensor.
Stergios Papadakis 1 , Thomas Mehoke 1 , David Deglau 1 , Mellisa Theodore 1 , Joan Hoffmann 1 , Lesly McAnelly 1 Show Abstract
1 Applied Physics Laboratory, Johns Hopkins University, Laurel, Maryland, United States
We describe a probe-target microarray biosensor in which the probe molecules are covalently bonded to the inner walls of anodic nanoporous alumina. Microarrays have a range of applications, from the identification of organisms or pathogens to determination of protein or gene function. The concept can be applied to wide array of probe-target systems. We have focused on nucleic acids for this report. A macroscopic nanoporous alumina substrate is lithographically patterned into individual array elements between of less than ten microns in diameter. Each array element contains a few hundred nanopores. Within each array element, all of the nanopores are functionalized with the same probe molecule. The nanopore diameter is selected such that when a target molecule binds to the probe, it significantly changes the mobility of ions through the pore. Detection of probe binding is performed by measuring the ionic mobility change in the sensor elements. No chemical labeling or modification of the target molecules is required.Commercially-available nanoporous alumina membranes were used for the experiments. We will describe the techniques for bonding the anodic alumina to a Si device wafer and for preparing the alumina for probe binding; the chemistries used for attaching the probe molecules and for the probe-target hybridization; and the electronic measurement geometry and technique. We demonstrate selectivity between complementary and non-complementary targets and electronic transduction via a simple AC impedance technique. The sensitivity of the device is expected to allow DNA fingerprinting without amplification of the target molecules. The electronic transduction can be performed at a wide range of moderate frequencies, 10 Hz to 100 kHz, allowing very simple electronics to perform the transduction in a future integrated label-free microarray sensor.
12:30 PM - TT2.5
Turbulence Resistant Perfluorocarbon Artifical Oxygen Carrier.
Agnes Ostafin 1 , Yen-Chi Chen 1 Show Abstract
1 Material Science, University of Utah, Salt Lake City, Utah, United States
As supplies of fresh donated blood continue to decline and the dangers of immunological mismatch, fear of disease and contamination persist, the need for artificial oxygen carriers (AOC) for surgery, traumatic injury, chronic anemia, and combat remains strong. The two leading classes of AOCs, polymeric hemoglobin and emulsified perfluorocarbons have encountered serious side effects, and thus new types of AOC are urgently needed. One approach to improving the clinical usefulness of PFC-based AOCs is to increase their circulation lifetime, thereby reducing the need for excess amounts to be added in order to compensate for physiological loss, and postponing the physiological burden of the AOC clearance until after the patient’s health crisis has passed. Such a material could be particularly useful for chronic conditions that benefit from AOC therapy, or conditions where hemoglobin-based therapy may generate other complications. Here, we describe a turbulence- resistant biocompatible PFC-based AOC nanoparticle synthesized from perfluorooctylbromide (PFOB) and 1,2 -dioleoyl-sn-glycero-3-phosphatidic acid (DOPA) lipid, emulsified by sonication or extrusion, and encapsulated by a thin shell of non-cytotoxic calcium phosphate. The thin shell strengthens the structure against breakup in turbulent liquid flow, but does not interfere with the oxygen carrying ability of the PFC. Measurements of electron and fluorescence microscope images, physical stability, erythrocyte hemolysis, oxygen carrying capacity, and the rate of permeation of oxygen across the shell of the AOCs indicate that these materials possess many characteristics essential for a viable AOC candidate.
12:45 PM - TT2.6
Natural Flexible Armor: Mechanical Properties of Individual Chiton Plates.
Matthew Connors 1 , Christine Ortiz 1 Show Abstract
1 Materials Science, MIT, Cambridge, Massachusetts, United States
Many animals possess exterior rigid armor units of various geometries (e.g. plates, scales, segments, shells, etc.) which are articulated together in unique ways so as to allow the construction of a complete or partial "flexible" exoskeleton. Such natural flexible armor enhances mobility and increases survivability against specific environmental and predatory threats. Studies of flexible armor in nature, in particular the balance between local mechanical protection mechanisms of the individual armor units and the larger length scale design principles of articulating armor-to-armor interconnections, hold great potential for the development of improved bio-inspired defense applications. In this research, a fascinating model flexible armor system was studied, the chitons (Mollusca, Polyplacophora). Unlike typical molluscs which have a single continuous shell, chitons have an exoskeleton that is composed of a single column of eight dorsal articulating calcareous plates (valves) surrounded by a leathery "girdle." These plates provide protection while still allowing for the flexibility needed for locomotion over heterogeneous surfaces. In this study, the structure and mechanical properties of the individual aragonite-based armor plates of Ischnochiton ruber were investigated. Optical microscopy, scanning electron microcopy (SEM), and atomic force microscopy (AFM), revealed the microstructures of four distinct layers composing the individual plates. The outermost tegmentum (~150 μm) possesses a fine-grained homogenous microstructure infiltrated by a complex network of channels containing light-sensitive organs. The second layer, the articulamentum (~200 μm) has a fine prismatic microstructure. The third layer (~150 μm) also possesses a fine-grained homogenous microstructure. Lateral projections of the second and third layer connect each plate to the surrounding girdle, while two “U”-shaped projections anchor each plate to its anterior neighbor. The bottom hypostracum consists of tablet-shaped crystals arranged in a crossed-lamellar fashion. Each first-order lamellae is oriented with its long axis perpendicular to the ventral shell surface. The second-order lamellae display two predominant oblique dip directions. X-ray diffraction data indicate that these two dip directions correspond to two grain orientations in which closed-packed planes of calcium ions are arranged parallel to the ventral shell surface. Spatially specific instrumented nanoindentation was employed to quantify the mechanical properties of individual armor plates through their cross-sectional thickness within the articulamentum and yielded average indentation moduli and hardness values of 90 GPa and 5.71 GPa, respectively. Ongoing and future work includes the use of these experimental data in a finite element computational model of the mechanical behavior of each plate, as well as the articulation between plates.
TT3: Systems & Interfaces I
Monday PM, November 30, 2009
2:30 PM - **TT3.1
From Nanostructured to Hierarchically Structured Functional Hybrid Organic-Inorganic Materials.
Clement Sanchez 1 2 Show Abstract
1 , CNRS-University of Paris VI, Paris France, 2 Chemsitry, UPMC/College de France, Paris France
Organized nanostructures and nanostructured materials often exhibit improved or even unique physical, chemical, and other properties. These specific properties are achieved through the design and the control of hybrid organic-inorganic interfaces. A new class of hierarchical structures has appeared after the first phase initiated by the sol-gel community. This new field of research is grounded on the comprehensive study of the material properties from the molecular to the nanometric or micronic scales. These were mainly dictated by applications from biological and chemical sensing, catalysis, energy, selective separation to optical communications etc. Many of these advanced inorganic and hybrid organic-inorganic materials synthesized via “chimie douce” are at the “cross-road” of inorganic chemistry, polymer chemistry, organic chemistry, and biology. Biomimetism and bioinspiration are smart tools for the design of innovative materials and systems that are strongly inspiring the materials chemistry community. Indeed, materials found in nature combine many wonderful features such as sophistication, miniaturization, hierarchical organizations, hybridation, resistance and adaptability. Elucidating the basic components and building principles selected by evolution to propose more reliable, efficient and environment respecting materials requires a multidisciplinary approach. The emerging new field coined “integrative materials chemistry” is opening not only new lands for innovative research but also should motivate or even give birth to passion for research to young scientists. This conference will present some of the general routes and innovative strategies that can be used to tailor made advanced hybrid organic-inorganic materials. Some of their properties will also illustrate this presentation. *Chimie Douce: a land of opportunities for the controlled designed construction of functional inorganic and hybrid inorganic-organic nanostructured materials. C. Sanchez, C. Boissiere, D. Grosso, C. Laberty, F. Ribot, L. Rozes , C. Sassoye and L. Nicole. Comptes Rendues Acad. Sciences Chimie, 2009.*Design, Synthesis, and Properties of Inorganic and Hybrid Thin Films Having Periodically Organized Nanoporosity. C. Sanchez, C. Boissiere, D. Grosso, C. Laberty and L. Nicole. Chem. Mater., 2008, 20, 682–737*Applications of hybrid organic–inorganic nanocomposites, C. Sanchez, M.Popall, B.Julian, P. Belleville. J. Mater. Chem., 2005, 15, 3559*Bio-Inspired Synthetic Pathways and Beyond: Integrative ChemistryE. Prouzet, S. Ravaine, C. Sanchez and R. Backov. New Journal of Chemistry, 2008, 32, 1284 *Photonic and *Nanobiophotonic properties of luminescent lanthanide-doped hybrid organic–inorganic materials.P. Escribano et al. J. Mater. Chem., 2008, 18, 23 *Biomimetism and bioinspiration as tools for the design of innovativematerials and systems C. Sanchez, M.M. Giraud Guille, H. Arribart. Nature Materials, 2005, 4, 277
3:00 PM - TT3.2
Synthesis of Functional Nanomaterials by Peptide Self-Assembly.
Jungki Ryu 1 , Joon Seok Lee 1 , Chan Beum Park 1 Show Abstract
1 Department of Materials Science & Engineering , Korea Advanced Institute of Science and Technology, Daejeon Korea (the Republic of)
The self-assembly of peptide-based building blocks is an attractive route for fabricating functional materials due to their unique features such as functional flexibility and molecular recognition as well as environmental compatibility. In this talk, we present the fabrication, characterization, and application of nanostructured peptide thin film by solid-phase self-assembly of diphenylalanine, which is one of best-known aromatic dipeptides having novel mechanical, electrochemical, and optical properties. We found that flat amorphous peptide thin film can be formed by simply drying a drop of diphenylalanine solution under anhydrous conditions. Evaporation of solvent during the preparation of amorphous film generated a gradient of chemical potential along the direction perpendicular to the substrate, and vertically aligned peptide nanowire film was formed by treating the amorphous peptide film with aniline vapor at high temperatures as high as 100 oC. The grown peptide nanowires had a uniform diameter of about 200 nm and a very high aspect ratio of at least 100 with a long persistence length over 10 μm. Furthermore, we were able to simultaneously fabricate a micro-pattern of peptide nanowires by combining a simple soft-lithographic technique and the high-temperature aniline vapor-aging process. Based on these results, we demostrate potential applications of our nanostructured peptide thin film like the fabrication of smart surfaces (e.g., self-cleaning superhydrophobic surfaces) and the synthesis of functional nanomaterials (e.g., conducting core/shell polymer nanowires). We believe that the dry process presented here will provide a new horizon for peptide-based nanofabrication because it can minimize problems occurring in conventional solution-phase methods.Our Recent Publications Related to This Presentation:J. Ryu, C. B. Park, Advanced Materials, Vol. 20, pp. 3754-3758 (2008).J. Ryu, C. B. Park, Chemistry of Materials, Vol. 20, pp. 4284-4290 (2008).J. Ryu, C. B. Park, Angew. Chem. Int. Ed., Vol. 48, pp. 4820-4823 (2009).J. Ryu, S. Y. Lim, C. B. Park, Advanced Materials, Vol. 21, pp. 1577-1581 (2009).J. S. Lee, J. Ryu, C. B. Park, Soft Matter, In press (DOI: 10.1039/b803770c, 2009)
3:15 PM - TT3.3
Optical Manipulation of Microtubules and Microtubule-based Templates for Directed Biomolecule Assembly.
Cerasela Zoica Dinu 1 , Douglas Chrisey 2 Show Abstract
1 Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, United States, 2 Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, Troy, New York, United States
For the directed nanofabrication of complex nanometer architectures and the development of next generation of nanodevices novel methods are required. Previous approaches to fabricate nanostructures were based on self-assembly of molecular or non-molecular components by non-covalent interactions, soft lithography or by electron-beam. Unfortunately, these approaches are time consuming, difficult to achieve when high densities of nanostructures are required on large surface, not totally user-controlled, and thus not efficient. To overcome these limitations, template-based self-assembly can provide a suitable mean. Biological systems are the ultimate example for the construction of highly complex structures and systems from simple and common building blocks used as scaffolds. Exploiting and manipulating this behavior in vitro would allow changing the paradigm of manufacturing. We used dynamic holographic optical tweezers (HOT) with various traps shapes (vertical or horizontal line traps, point and Bessel traps) to efficiently manipulate individual microtubules or template hybrid complexes formed from microtubules and quantum dots in three dimensions and on engineered surfaces in view of forming user-controlled architectures. Microtubules are non-covalent polymers formed from heterodimers of alpha and beta-tubulin with lengths reaching µm and an outer diameter of ~ 25 nm. Microtubule play roles in cell division, intracellular transport, and reconfiguration by direct assembling into bundles in protozoa, and mitotic spindles in eukaryotic cells. Our ability to simultaneously manipulate distinct microtubule by computer-controlled holograms i.e., move the objects in three dimensions at microns/sec speeds, with 15 nm resolution, and with rotational capability, while also exploiting their natural thermodynamic spontaneity towards self-assembly may provide a totally unique approach to efficient nanomanufacturing for subsequent engineering and biomedical applications. We also tested the possibility of forming for the first time user-directed architectures with individual traps. For this, two independent microtubule-QDots complexes were brought in contact and allowed to interact. Further attempts manipulated the resulting user-directed architecture with a single trap. Our results establish a novel platform for the supramolecular assembly formation by three-dimensional manipulation of biological or hybrid-derived materials. This strategy can be used for the automated nanofabrication of macromolecular architectures and development of novel template-based hybrid materials.
3:30 PM - **TT3.4
Systems and Interfaces for Controlling Bioprocesses: An Example.
Galen Stucky 1 , April Sawvel 1 , Sarah Baker 1 , Christopher Knoll 1 Show Abstract
1 , University of California, Santa Barbara, California, United States
The dynamic and often subtle interactions among organic and inorganic species and/or organized arrays covers a wide kinetic and thermodynamic phase space that offers almost unlimited opportunities to synthesize hierarchical multifunctional systems; and, to subsequently selectively use the interface chemistry to modify bioprocesses. This talk will focus on some recent research on the use of inorganic species to control bioprocesses, specifically the development of a protocol to accelerate or inhibit blood coagulation by using inorganic-blood interface chemistries that selectively control local protein and blood-cell chemistry, electrolyte accessibility, local dehydration driven concentration profiles, and changes in local blood temperature. A more-detailed working understanding of the chemistry interface between the inorganic surface and the blood protein factors that are part of the blood-clotting cascade can be arrived at by adding to or depleting the blood-factor component concentrations that are associated with the blood-clotting system chemistry, including the presence or absence of external agents such as anticoagulants. The inorganic interface and pore structure can be selectively defined to be protein-size accessible so that in a high-surface-area form, the materials can be used as an active enzyme support or other large-molecule delivery agent to the blood system. Smaller pore configurations can be used for electrolyte and antibacterial agent delivery. The inorganic surface acid/base properties, hydrophobicity, charge and isoelectric point are potentially important variables that can be readily modified. Understanding the relative roles of blood and inorganic composition on thrombosis and anticoagulation are interesting challenges in a system that is auto-catalytic and self-regulating, and capable of both hemostatic and bone-forming activity. The correlation and use of in vitro research and in vivo testing for potential commercial applications will be summarized.
TT4: Functional Nanoparticles I
Monday PM, November 30, 2009
4:30 PM - TT4.1
“Backpack” Functionalized Living Immune Cells.
Albert Swiston 1 , Darrell Irvine 1 3 , Robert Cohen 2 , Michael Rubner 1 Show Abstract
1 Materials Science and Engineering, MIT, Cambridge, Massachusetts, United States, 3 Biological Engineering, MIT, Cambridge, Massachusetts, United States, 2 Chemical Engineering, MIT, Cambridge, Massachusetts, United States
We demonstrate that multi-functional “backpacks” built from polyelectrolyte multilayers (PEM) films can be attached to living immune system cells including lymphocytes and dendritic cells (DCs). Fabricated using standard photolithographic techniques, 7 micron diameter backpacks are built on a glass surface and consists of 3 distinct regions. The first is a releasable region comprised of a poly(methacrylic acid)/poly(vinylpyrrolidone) hydrogen-bonded multilayer that will dissolve above pH 6.4 and release the backpack from the substrate. The next region is the payload and consists of Fe3O4 nanoparticles and FITC-labeled poly(allylamine hydrochloride) rendering the backpacks both magnetic and fluorescent. Last, a cell-adhesive outer face is chosen based on the cell of interest to anchor the backpack to the membrane. For example, we have used hyaluronic acid (HA)-containing PEMs to anchor backpacks to B-lymphocytes, since HA is the ligand for CD44, a surface receptor found on these cells. Since these backpacks do not completely occlude the cellular surface from the environment, this technique allows payloads to be attached to a cell that is still free to perform its native functions requiring intimate environmental interaction. For instance, we have shown that patch-modified T-cells remain able to migrate on ICAM-coated coverslips and DCs are able to attach and spread on TCPS dishes. Possible payloads within the PEM patch include drugs, vaccine antigens, thermally responsive polymers, and nanoparticles which may be delivered by the cell to a site for interest or foment some phenotypical change in the attached cell. We will discuss how this approach has broad potential for applications in bioimaging, single-cell functionalization, immune system and tissue engineering, and cell-based therapeutics.
4:45 PM - TT4.2
The Binding of Magnetic Nanoparticles to Biological Templates.
Hyun-Cheol Lee 1 , Jing C. Zhou 1 , Bruce Dunn 1 Show Abstract
1 Materials Science and Engineering, Univeristy of Calilfornia, Los Angeles, Los Angeles, California, United States
We are interested in assembling discrete, nanoscale magnetic particles for logic and memory device applications. In this study, we use microtubules (MTs) biological templates to provide a non-lithographic method for assembling magnetic nanoparticles. This approach bypasses the limitations of conventional top-down lithographic processes as our goal is to assemble nanoparticles at dimensional scales less than 100 nm. Arrays of cobalt nanomagnets on insulating MTs have been successfully fabricated by an electroless plating method. The first step of the process is to expose the MTs to a Pd solution adjusted to pH ~ 6.3. Positively charged Pd cations effectively attach to the negatively charged MT surface. This is followed by the addition of a CoSO4 solution, which contains a reducing agent such as dimethylamine bromide (DMAB). In this way, the Co2+ is reduced to Co0 on the Pd activated MT surface. We have investigated the use of various chelating agents to control the morphology of cobalt nanoparticles and the spacing between the nanoparticles on the MT. The use of adipic acid as a chelating agent is particularly effective in producing a quasi-periodic arrangement of Co nanoparticles with ~ 2 nm spacing. SQUID measurements of MT templated Co nanoparticles revealed ferromagnetic behavior at 298 K. The very strong magnetic interaction between particles indicates the feasibility of constructing nano-sized magnetic devices on a biotemplate.
5:00 PM - **TT4.3
Designed Fabrication and Assembly of Uniform-sized Nanoparticles for Multifunctional Biomedical Applications.
Taeghwan Hyeon 1 , Yong Il Park 1 , Nohyun Lee 1 , Hyon Bin Na 1 , Yuanzhe Piao 1 , Jeong Hyun Kim 1 , Ji Eun Lee 1 Show Abstract
1 School of Chemical and Biological Engineering, Seoul National University, Seoul Korea (the Republic of)
Combinations of various nanostructured materials can offer multifunctional nanomedical platforms for multimodal imaging, and simultaneous diagnosis and therapy. We synthesized hollow magnetite nanocapsules via wrap/bake/peel process and used them for both the MRI contrast agent and magnetic guided drug delivery vehicle. We reported on the fabrication of monodisperse nanoparticles embedded in uniform pore-sized mesoporous silica spheres for simultaneous MRI, fluorescence imaging, and drug delivery. We fabricated magnetic gold nanoshells consisting of gold nanoshells that are embedded with Fe3O4 nanoparticles for simultaneous NIR photothermal therapy and MRI. NaGdF4:Er3+,Yb3+/NaGdF4 upconverting nanoparticles (UCNPs) can serve as multimodal imaging probe not only for background-free optical imaging but also for MRI.
5:30 PM - TT4.4
Synthesis of High Density Metallic and Semiconducting Nanoparticles on a Cellulose Template.
Sonal Padalkar 1 2 , Lia Stanciu 1 2 , Robert Moon 1 2 Show Abstract
1 Material Science and Engineering, Purdue University, West Lafayette, Indiana, United States, 2 Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana, United States
High density metallic (silver, copper, gold, platinum) and semiconducting (cadmium sulfide, zinc sulfide, lead sulfide) nanoparticles were synthesized, for the first time, on the cellulose template by manipulating the surface charge on the template. The density of the nanoparticles could be varied by varying the surface charge on the template. The size of the nanoparticles on the template could also be varied, from ~7nm to ~75nm, by varying the process parameters. These high density nanoparticles were characterized by FESEM, TEM, HRTEM, EELS and elemental mapping.
5:45 PM - TT4.5
Fluorescent Ag Clusters Self-assembled on DNA Nanostructures.
Patrick O'Neill 1 , Kevin Young 1 , Elisabeth Gwinn 1 , Deborah Fygenson 1 2 Show Abstract
1 Physics, UC Santa Barbara, Santa Barbara, California, United States, 2 Biomolecular Science and Engineering, UC Santa Barbara, Santa Barbara, California, United States
Few-atom Ag clusters self-assemble on single-stranded DNA, yielding sequence-dependent fluorescence from the blue to the near-infrared. We show that these fluorescent clusters can be made at specific locations on DNA nanostructures by incorporating DNA hairpins at programmed locations. We discuss fundamental aspects of these clusters, such as the number of atoms in the cluster and the nature of the excited states, as well as practical aspects such as chemical yields, quantum yields, and Mg++ dependent properties.
TT5: Poster Session
Monday PM, November 30, 2009
Exhibit Hall D (Hynes)
9:00 PM - TT5.1
Enhanced Nanomachine Based on Fullerene/DNA Hybrids.
Su Ryon Shin 1 , Kyeong Sik Jin 2 , Chang Kee Lee 1 , Geoffrey M. Spinks 3 , Ji Young Mun 4 , Sung-Sik Han 4 , Moonhor Ree 2 , Seon Jeong Kim 1 Show Abstract
1 , Hanyang University, Seoul Korea (the Republic of), 2 , Pohang University of Science and Technology , Pohang Korea (the Republic of), 3 , Intelligent Polymer Research Institute, Wollongong, New South Wales, Australia, 4 , Korea University, Seoul Korea (the Republic of)
Molecules that actuate a specific response are thought of as the functional components of future nano-devices. For example, nano-assemblers and nanobots will require molecular-sized motors that can work efficiently in generating motion and moving mass. DNA is considered a versatile building block for such molecular-machines because of its well defined structure and controllable intermolecular interactions. Several excellent reviews describe the application of DNA for the controlled self assembly of three-dimensiona nano-structures and nano-mechanical devices. We are particularly interested in improving the usefulness of DNA nanomachines by improving their basic mechanical and switching functions and stability. Chemical functionalization of DNA can influence the inter- and intra-molecular bonds and, therefore, the stable molecular conformations. Here we show that the attachment of fullerenes to a DNA motif significantly improves its molecular switching and stability of this pH driven enthalpic molecular-machine. Our objective was to follow in detail the molecular conformation changes occurring in a DNA motif using three-dimensional molecular analysis by SAXS. Hydrophobic interactions between the terminal fullerenes in the folded i-motif conformation increased the machines power stroke and force generated. No reduction in cycling speed or cycling stability with changing pH was observed as a result of attachment of the fullerene. These results are important for the development of future molecular machines, since they demonstrate for the first time that fullerene attachment does not necessarily disrupt the function of the molecular motor. The study reported here and future work increase the possibility of developing molecular machines capable of moving a defined nanoparticle for molecular assembly / chemistry, controlled molecular interactions and even propulsion systems for mobile nano-devices.
9:00 PM - TT5.10
Immunodetection of Cancer Marker in Human Serum Using Silicon Field Effect Transistors.
Chil Seong Ah 1 , Ansoon Kim 1 , Chanwoo Park 1 , Jong-Heon Yang 1 , Tae-Youb Kim 1 , Chang-Geun Ahn 1 , Gun Yong Sung 1 Show Abstract
1 , Electronics and Telecommunications Research Institute (ETRI), Daejeon Korea (the Republic of)
Label-free and real-time prostate specific antigen (PSA) sensor has been developed using p-type silicon field-effect transistor (FET) where the conventional “top-down” semiconductor processes were employed to make nanostructures. We have detected the PSA as a marker for prostate cancer in undiluted human serum with high salt concentration (~150 mM) using the Si-FET. To detect the PSA, the monoclonal antibody of PSA (anti-PSA) has been immobilized on the Si surface through covalent linkage using specific surface chemistry. Specific binding of PSA with the anti-PSA on p-type Si-FET channels leads to a conductivity change in response to variations of electric field at the surface, which results in label-free and real-time immunodetection. It has been known that detecting a target antigen in human serum is difficult because of short Debye screening length of the serum with high salt concentration. In this presentation, we discuss new detection method of the target antigen, PSA, in human serum and show quantitative detection results of PSA in human serum from 1 ng/mL to 100 ng/mL using the Si-FET sensor. AcknowledgementThis work was partly supported by the Ministry of Knowledge Economy in Korea [2006-S-007-04, Ubiquitous Health Monitoring Module and System Development] and the KOCI [09ZC1410, Basic Research for the Ubiquitous Lifecare Module Development].
9:00 PM - TT5.11
The Combination of Drug or Gene Delivery System Responding to Cellular Signals (D-RECS) and Sonoporation System for Effective and Safe Gene Delivery.
Akira Tsuchiya 1 , Takeshi Mori 1 2 , Yuki Naritomi 1 , Jeong-Hun Kang 1 , Daisuke Asai 3 , Takuro Niidome 1 2 , Yoko Endo 4 , Ryo Suzuki 5 , Yoichi Negishi 4 , Kazuo Maruyama 5 , Yoshiki Katayama 1 2 Show Abstract
1 Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, Fukuoka, Japan, 2 Center for Future Chemistry, Kyushu University, Fukuoka, Fukuoka, Japan, 3 Department of Microbiology, St. Marianna University, Kawasaki, Kanagawa, Japan, 4 Department of Drug and Gene Delivery System, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachiouji, Tokyo, Japan, 5 Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa, Japan
Gene therapy has been expected as promising tool to treat congenital gene diseases, infectious diseases, and malignant tumors. In gene therapy, the effectiveness and safety of the gene delivery systems are very important property. To improve safety and therapeutic effects, therapeutic genes should be expressed in disease cells, but not normal cells. Recently, we developed a new drug delivery system called drug or gene delivery system responding to cellular signals (D-RECS). This system uses abnormally activated intracellular target signals as a trigger to release the gene from the carrier and thus to activate gene expression. For example, protein kinase Cα (PKCα) is widely accepted its hyperactivation in many tumors and plays key roles in proliferation of tumors such as melanoma, hepatoma and breast cancer. Specifically, we designed a PKCα-responsive polymer containing a neutral polymer as the main chain and a cationic substrate peptide for PKCα as side chains. This polymer forms a stable complex with plasmid DNA (pDNA) through electrostatic interaction. In this complex, the gene transcription is totally suppressed. The polymer/pDNA complex can be transferred into melanoma cells via endocytosis and be collapsed responding to activated PKCα. Thus, gene expression is activated only in tumor cells. We succeeded regulating gene expression responding to activated PKCα in various cancer cell lines, but in some cells, we couldn’t identify gene expression in spite of activation of PKCα due to the poor endocytosis activity. To resolve this problem, we tried to combine D-RECS with sonoporation system to improve transfection efficiency. Sonoporation system is a method of gene delivery with ultrasound. A combination of ultrasound and microbubble echo contrast agents is shown to enhance gene transfection efficiency.
First, we synthesized acrylamide-base PKCα-responsive polymer (polymer 1) containing substrate peptides of PKCα (FKKQGSFAKKK) and a negative control polymer (polymer 2), in which the phosphorylation site serine was changed to alanine (FKKQGAFAKKK) as side chains. Then, the polymer/luciferase-encoded pDNA complex with microbubble was added to A549 cells and transferred into cells using sonoporation under the optimal transfection condition (frequency : 1 MHz, intensity : 1.5 W/cm2, Duty cycle : 50%, time : 5 s). At 24 h after transfection, luciferase activities were assessed. Very low gene expression was identified in the absence of sonoporation. On the other hand, in the presence of sonoporation, remarkable enhancement of gene expression was observed. In contrast, polymer 2/pDNA showed only very low level of expression even in the combination with sonoporation. These results suggested that the combination of our PKCα-responsive system and sonoporation is efficient for cancer-specific gene therapy and imaging.
9:00 PM - TT5.12
Oligonuleotide Delivery with Dendritic Poly(L-lysine) for Treatments of the Liver Disorders.
Kazuto Watanabe 1 , Mariko Shiba 2 , Akira Suzuki 2 , Yuriko Higuchi 3 , Shigeru Kawakami 3 , Mitsuru Hashida 3 4 , Risa Gokuden 1 , Ryohsuke Kurihara 1 , Sugao Yusuke 1 , Takeshi Mori 1 , Yoshiki Katayama 1 5 , Takuro Niidome 1 5 6 Show Abstract
1 Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka Japan, 2 Bioscience, National Cardiovascular Center Research Institute, Suita, Osaka Japan, 3 Drug Delivery Research, Kyoto University, Kyoto Japan, 4 Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto Japan, 5 Center for Future Chemistry, Kyushu University, Fukuoka Japan, 6 PRESTO, Japan Science and Technology Corporation, Kawaguchi Japan
Lots of oligonucleotide-based drugs have been expected and developed to control specific gene expression. Especially, decoy oligonucleotide and siRNA have attracted much attention as nucleotide drugs. To apply them to clinical use, it is necessary to develop efficient in vivo delivery system of the oligonucleotides, and lots of oligonucleotide carrier molecules such as cationic lipids and polymers have been reported.
We previously reported that a sixth generation of dendritic poly(L-lysine) (KG6) had high plasmid DNA or siRNA transfection ability with low cytotoxicity in vitro. The efficiency was comparable to commercially available transfection reagents such as Lipofectin, JetPEI, and Superfect. We recently investigated the biodistribution of plasmid DNA delivered with KG6 in mice after intravenous administration and revealed that more than 20% of the intact plasmid DNA had accumulated in the liver (T. Kawano et al., J. Control. Release, 99, 329-337, 2004). Taking advantage of the dendritic poly(L-lysine) that deliver the nucleic acids to the liver, we tried to apply it as a carrier for decoy and siRNA delivery to the liver. As model diseases, we chose hypercholesterolemia and hepatitis. In this study, we employed siRNA that inhibits apolipoprotein B (ApoB) expression for hypercholesterolemia and NF-κB decoy for hepatitis treatment, and evaluated effect of the oligonucleotides after intravenous injection of their complex with KG6.
ApoB plays important role for controlling very-low-density lipoprotein (VLDL) and low-density lipoproteins (LDL) level in the blood. Therefore, down regulation of ApoB activity with siRNA enables us to treat severe hypercholesterolemia. We prepared 50 μg of siRNA complex with KG6 at C/A ratio of 8, and then intravenously injected into Apolipoprotein E deficient mice, which were widely used hypercholesterolemic mouse model. A single dose of the siRNA complex resulted in a decrease in VLDLc and LDLc levels for up to 96 hours, whereas no decrease in their levels was observed with the 5% dextrose only or the control siRNA complex.
NF-κB decoy is expected as an anti-inflammation drug because it blocks a cascade of cytokine induction that triggers the inflammation. Therefore, efficient delivery system of the decoy oligonucleotide into the liver could be an important technique for treatment of hepatitis. KG6 formed a complex with the NF-κB decoy. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were dramatically suppressed by intravenous administration of KG6/NF-κB decoy complex in lipopolysaccharide /D-galactosamine-induced hepatitis mice. Expression levels of several cytokines and proteins related to the inflammatory reaction were also suppressed (Y. Sugao et al., Bioorg. Med. Chem., in press ,).
9:00 PM - TT5.13
DNA-Mediated Assembly of Gold Nanoparticles and Restriction Enzyme-Induced Disassembly: Particle Size and DNA Length Effects.
Elizabeth Crew 1 , Martha Kamundi 1 , Stephanie Lim 1 , Uma Chandrachud 2 , Susannah Gal 2 , Chuan-Jian Zhong 1 Show Abstract
1 Department of Chemistry , State University of New York at Binghamton, Binghamton, New York, United States, 2 Department of Biological Sciences, State University of New York at Binghamton, Binghamton, New York, United States
The ability to manipulate and intervene in the processes of assembly and disassembly of DNAs and nanoparticles is important for the exploitation of nanoparticles in medical diagnostics and drug delivery. We have recently demonstrated the viability of intervening the assembly and disassembly processes of DNAs and gold nanoparticles based on specific biorecognition. The biomolecular intervention is found to be highly dependent on the interparticle structures and interactions. This presentation will discuss recent results of our investigation of the particle size and DNA length effects on the interparticle structures and interactions for the DNA-mediated assembly of gold nanoparticles and restriction enzyme-induced disassembly processes. Highly-monodispersed nanoparticles with sizes ranging from 10 nm to 80 nm and DNAs with base pairs ranging from 15 to 35 are studied as model systems. Implications of the results to the design and control of the interparticle interactions and reactivites in the DNA-nanoparticle systems will also be discussed.
9:00 PM - TT5.14
Influence of Metal Nanoparticle Surface Chemistry on the Block Copolymer- Nanoparticles Hybrid Self-assembly Behavior.
Hiroaki Sai 1 , Zihui Li 2 , Tatsuro Morimoto 3 , Scott Warren 4 , Jin Yi Ryu 5 , Ulrich Wiesner 1 Show Abstract
1 Department of Materials Science and Engineering, Cornell University, Ithaca, New York, United States, 2 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, United States, 3 Department of Applied Chemistry, Kyushu University, Fukuoka, Fukuoka, Japan, 4 Laboratory of Photonics and Interfaces , Ecoles Polytechniques Fédérale de Lausanne, Lausanne, CH, Switzerland, 5 Department of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, United States
Ordered metal nanostructures with tailored length scales, morphologies, and selection of metal species have gained widespread interest as catalysts in energy conversion and storage and as novel optical metamaterials. In recent work, Warren et al. showed that platinum-dense nanostructures can be self-assembled with amphiphilic block copolymers by functionalizing the platinum nanoparticles with protecting ligand molecules that have ionic character and steric hindrance . Here we present the effect of varying metal species, ligands and polymer block functionalities on the nanostructured hybrid formation of metal nanoparticles with amphiphilic block copolymers. By tuning the nanoparticle surface-polymer block interactions and ligand-block polymer interactions as well as preventing nanoparticle-nanoparticle attraction with ligand molecules, we investigate the thermodynamic implications of metal nanostructure formation and look toward a generalized process for mixed metal nanostructures.References1.Warren, S. C.; Messina, L. C.; Slaughter, L. S.; Kamperman, M.; Zhou, Q.; Gruner, S. M.; DiSalvo, F. J.; Wiesner, U., Ordered mesoporous materials from metal nanoparticle-block copolymer self-assembly. Science 2008, 320 (5884), 1748-1752.
9:00 PM - TT5.15
A Comparative Study of Magnetic Properties in Well Dispersed and Conjugated Iron Oxide Nanoparticles.
Yuan Yuan 1 , Diana-Andra Borca-Tasciuc 1 Show Abstract
1 Mechanical Engineering, Rensselear Polytechnic Institute, Troy, New York, United States
Magnetically-mediated hyperthermia, which employs magnetic nanoparticles heated by alternating magnetic field, is receiving considerable interest as a potential therapy for cancer treatment. To develop and optimize materials for cancer hyperthermia applications it is essential to understand the effect of nanoparticles clustering on magnetic properties and respectively heat generation rate. While most of the existing studies focused on well dispersed nanoparticle systems, in practice nanoparticles may cluster as they are internalized by the cells or agglomerate on the cellular membrane. In this context, measurements on susceptibility and magnetization of well dispersed and respectively clustered iron oxide nanoparticles are reported. Iron oxide nanoparticles functionalized with amine and respectively carboxyl group are conjugated through standard EDC reaction to facilitate clustering. Susceptibility and magnetization measurements are carried out employing a differential impedance method.
9:00 PM - TT5.16
Photostability of DNA Encapsulated Laser Dye.
Yogesh Ner 1 , Daminda Navarathne 1 2 , James Grote 3 , Gregory Sotzing 1 2 Show Abstract
1 Polymer Program , University of Connecticut, Storrs, Connecticut, United States, 2 Department of Chemistry , University of Connecticut, Storrs, Connecticut, United States, 3 , US Air Force Research Laboratory, Wright-Patterson Air Force Base, Ohio, United States
The properties of organic dyes inside thin polymeric films are important as it directly alters their performance for use in solid-state dye lasers, displays, sensors and optical amplifiers. The optical gain of these thin films is limited by the amount of dye loading as higher dye loading results in formation of non-fluorescent aggregates. Another important aspect relates to the permanent destruction of luminance of organic dyes under repeated excitation due to photodegradation. Encapsulating dye molecules in confined media such as mesoporous silica, and dendrimers is an attractive approach to improve both photophysical and photochemical properties by providing population isolation and conformational restriction to the dye. However, major advantages of using polymeric hosts such as ease in fabrication and low cost may not be accessible. Herein, we provide a simplified strategy to access the encapsulation effects in DNA thin films. DNA when complexed with cationic surfactant, forms organically processable material which can be cast into uniform thin films by spincoating. DNA also has the ability to specifically interact with planar aromatic molecules, including several laser dyes. Such a configuration can lead to population isolation as well as confirmation restriction thereby providing improvement in both photophysical and photochemical properties. We will demonstrate this phenomenon using a non-linear optical dye Hemi-22 doped in DNA thin films. Hemi-22 is a organic soluble dye which is reported to bind with DNA by minor grove binding. We have observed that by using DNA as an encapsulation matrix it is possible to load a higher amount of dye without any observable aggregation. This property also resulted into fluorescent enhancement of the dye compared to a conventional polymer matrix. Furthermore, binding of Hemi 22 with DNA leads to an increase in the fluorescence lifetime of the dye. Consequently the combined effects of dye isolation and confinement resulted in significant improvement in the photostability of the dye in the presence DNA. We will discuss the effects of dye loading and role of DNA on photostability of Hemi-22 under UV illumination.
9:00 PM - TT5.17
Radiation Effects in Cerium Oxide Studied by Experiment and Simulation.
Amit Kumar 1 , Satyanarayana Kuchibhatla 2 , Vaithiyalingam Shutthanandan 2 , Ram Devanathan 3 , Suntharampillai Thevuthasan 2 , Ajay Karakoti 1 , Sudipta Seal 1 Show Abstract
1 NanoScience Technology Center, Advanced Materials Processing and Analysis Center, Mechanical Materials and Aerospace Engineering , University of Central Florida, Orlando, Florida, United States, 2 Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, United States, 3 Chemical & Materials Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States
Associated with beneficial effects of radiation in therapy is the unavoidable risk of damaging healthy cells by excess free radicals generated due to high energy ionizing radiation. Cerium oxide nanoparticles have shown the ability to quench the free radicals and reactive oxygen species by regenerative switching between the 3+ and 4+ valence state. Ceria nanoparticles (and their hybrids) and thin films were synthesized by chemical synthesis and molecular beam epitaxy, respectively and exposed to He+ radiation in the range of 1-8 MeV for different exposure time using the ion beam accelerator at EMSL, in Pacific Northwest National Laboratory. The chemical changes in nanoceria particles and thin films due to radiation exposure were characterized in situ by X-ray photoelectron spectroscopy to understand any changes in the chemistry. The relative ratio of Ce3+/Ce4+ was estimated before and after the radiation exposure by analyzing Ce 3d spectra. The physico-chemical effects of radiation exposure to ceria was further explored by molecular dynamics simulation. The theoretical study provides insight into defect processes in cerium oxide. The redox chemistry and structural changes of nanoparticles and thin films due to radiation exposure will be discussed in detail along with implications to the use and engineering of cerium oxide and their hybrids in future nanomedicine.
9:00 PM - TT5.18
Effects of Magnetic Nanoparticles on Magnetic Resonance and Spin Relaxation in Systems of Different Viscosity.
Natalia Noginova 1 , Aleksandr Andreyev 2 , Julia Noginova 3 , Joseph Hall 1 , V. Ramesh 1 , V. Atsarkin 4 Show Abstract
1 , NSU, Norfolk, Virginia, United States, 2 , Virginia Tech, Blacksburg, Virginia, United States, 3 , PAHS, Virginia Beach, Virginia, United States, 4 , IRE, Moscow Russian Federation
Magnetic nanoparticles are promising in various medical applications such as MRI contrast agent and medical hyperthermia. As was demonstrated earlier, nanoparticle-related effects on the magnetic resonance spectra and spin relaxation are different in solid and liquid systems. To better understand the behavior in cases of intermediate viscosity, including biological systems, NMR spectra and spin relaxation times have been studied in model systems and live cell cultures. The applicability and boundaries of the outer sphere model are discussed.
9:00 PM - TT5.19
Electrochemical Detection of Glycoproteins and the Effect of Biogenic Silica Based Nanopores.
Srivatsa Aithal 1 , Bothara Manish 4 , Kai-Chun Lin 3 , Vinay Nagaraj 2 , B. Ramakrishna 3 , Shalini Prasad 2 Show Abstract
1 Electrical Engineering, Arizona State University, Tempe, Arizona, United States, 4 Electrical and Computer Engineering, Portland State University, Portland, Oregon, United States, 3 School Of Materials, Arizona State University, Tempe, Arizona, United States, 2 Center for Applied NanoBioscience, The Biodesign Institute, Arizona State University, Tempe, Arizona, United States
The aim of this project is to design a nanotextured, electrical, label-free detection system for detection of clinically relevant low doses of glycans. Electrical and label-free detection helps us reduce the cost of the system. Research indicates that improved detection parameters such as high sensitivity and selectivity can be achieved in electrical detection by employing size based confinement techniques in nanomaterials. We use diatom to confine the biomolecules in our sensors. These are eukaryotic algae, whose silica cell walls are called frustule. The frustules have fine pores in the order of nanometers. The frustules are layered over our sensor surface, which enhances our electrical signal due to nanoscale confinement and macromolecular crowding of biomolecules.Our sensor detects Glycans using Electrochemical Impedance Spectroscopy in which the impedance between the electrodes at different frequency points are measured. This frequency response changes with the property of the nanolayers on the electrode, we use this property to detect the glycoprotein binding on the sensor surface. We use a layer by layer chemistry to bind the lectin to the sensor surface which in turn acts as the detection site, specifically binding to the conjugate glycoprotein. The specificity of detection is due to the specificity of the glycoprotein lectin bond. Our sensor reduces the sensing time to a fourth of the standard assay while providing robust sensitivity. The sample volume in our sensor is in tens of microliters, which is significantly less than in the standard detection methods.
9:00 PM - TT5.2
Hybrid Nanomaterial Scaffolds for Specific Biomedical Applications.
Mandar Gadre 1 , Jianing Yang 1 , Ted Lin 2 , Frederic Zenhausern 1 Show Abstract
1 Center for Applied Nanobioscience, Biodesign Institute, Arizona State University, Tempe, Arizona, United States, 2 , Corona del Sol High School, Tempe, Arizona, United States
Nanomaterials such as aerogels and xerogels have a broad potential for various applications, due to their controllable properties like pore-size, pore-size distribution, large surface area, tailorable surface chemistry and mechanical strength. Such range of properties make them some of the best candidates for many specific biomedical applications such as tissue engineering, sample collection applicators and engineered microenvironments for three-dimensional cell culture. We are working with templated hybrid organic-inorganic scaffolds made of aerogels. This is a very interesting class of materials, with their amazingly broad tailorability of properties arising from the highly flexible processing route of sol-gel methods. In the present study, macroporous organic-inorganic hybrid aerogels are fabricated from siloxane precursors. Various organic polymers are incorporated to achieve different combinations of physical properties. The macroporosity obtained through the use of templating agents is crucial in cellular applications. The mechanical strength required of a scaffold for cell culture is achieved by cross-linking the silica network with organic polymers like diisocyanates and polymethyl methacrylate. The surface chemistry suitable for cell viability and proliferation is brought about by using different organic derivatives of the siloxane precursors. The aerogels thus fabricated are tested for their stability in solvents like water and biological buffers. The imaging is carried out by Scanning Electron Microscopy. The amorphous nature of the aerogels is confirmed by X-ray Diffraction. The surface area measurements are done using Nitrogen Gas Adsorption methods employing the BET theory. Average pore size and pore-size distribution are studied using Mercury Porosimetry. The materials characterization is followed by demonstration of their potential applications in the biomedical field, including the co-culturing with human cervical cancer cell line, SiHa cells on the aerogel scaffolds; and collecting and transporting biological samples. The co-culture is monitored for cell viability, morphology and proliferation. The imaging is carried out with an optical microscope. The collection and transfer properties of the aerogels are evaluated by the quantity and quality of the DNA fragments extracted from blood samples collected by aerogels. Our preliminary observations and results of multiple length-scale phenomena with in vivo-like qualities that mimic change in cell morphology, contact geometries and transport properties in specific types of scaffolds will be presented in the meeting.
9:00 PM - TT5.20
Targeted Killing of Pancreatic Cancer Cells with Epidermal Growth Factor.
Alokita Karmakar 1 , Meena Mahmood 1 , Ashley Fejleh 1 , Philip Fejleh 1 , Yang Xu 1 , Enkeleda Dervishi 1 , Anindya Ghosh 1 , Samuel Collom 1 , Samar Hassan 1 , Teodora Mocan 2 , Cornel Iancu 2 , Lucian Mocan 2 , Dana Iancu 2 , Alexandru Biris 1 Show Abstract
1 , University of Arkansas at Little Rock, Little Rock, Arkansas, United States, 2 , University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca Romania
Carbon nanotubes can be conjugated with biomolecules and the resultant conjugated entities can be delivered to different cells. Delivering therapeutically active molecules to particular cells is one of the major areas of research. Such specific delivery can reduce unwanted side effects of numerous toxic drugs such as chemotherapeutic agents to kill cancer cells. EGF, a growth factor , have several receptor on the surface of the cell which help docking the carbon nanotubes on the cell surface and thus overall help easy internalization. EGF receptor is overexpressed in several human carcinomas compared to their healthy counterpart including pancreatic cancer. In this work, we have shown that single walled carbon nanotubes (SWNTs) covalently linked to Epidermal Growth Factor (EGF) can easily cross the pancreatic cancer cell wall and get internalized. Pancreatic cancer cells were incubated with different concentrations of SWNTs conjugated with EGF. Confocal microscope and Enzyme Linked Immunosorbent Assay (ELIZA) was used to visualize and quantify the EGF-SWNTs. We found that 5microg/ml (EGF-SWNTs) is the best concentration at which most of the EGFs were internalized. Within 5 second, most of the EGF was getting associated with pancreatic cancer cells and then they started to dissociate. Thus the current approach provides the opportunity of delivering nanotube conjugate more specifically to the cancer cells.
9:00 PM - TT5.21
Optimizing Hybrid Bionanodevices by Understanding Protein-Surface and Receptor-Ligand Interactions.
Ashutosh Agarwal 1 , Parag Katira 1 , Thorsten Fischer 1 , Henry Hess 1 2 Show Abstract
1 Materials Science and Engineering, University of Florida, Gainesville, Florida, United States, 2 Biomedical Engineering, Columbia University, New York, New York, United States
Hybrid bionanodevices utilize biological nanoscale components to provide critical functions in a synthetic environment. For example, “smart dust” biosensors are enabled by kinesin-powered molecular shuttles. These shuttles consist of antibody-functionalized microtubules, which are propelled by kinesin motor proteins patterned on a surface in engineered tracks. Two key challenges in the design of such hybrid bionanodevices are the control of protein-surface interactions, here to achieve well-defined patterns of adsorbed kinesin, and the understanding of receptor-ligand interactions, here to obtain efficient attachment of cargo to the shuttle. Our investigations of these challenges have led to novel theoretical insights into the nature of these problems and have enabled the design of a functional “smart dust” biosensor. Spatial confinement of shuttle motility within defined track regions requires control over motor adsorption on surfaces. This implies that the kinesin density in the non-track region has to be less than one motor per µm2 (~ 0.05 ng/cm2) to prevent escape of the microtubule from the track region. This protein coverage challenges both the state of the art for synthesizing non-fouling surfaces as well as the detection limit of current protein density measurement techniques (~ 1 ng/cm2). We have developed a new characterization technique which lowers the detection limit hundred-fold. In this technique, the landing rate of fluorescently labeled microtubule probes on a kinesin-coated test surface is measured to determine the kinesin density on the surface. We are currently improving this method to develop a generalized protein density measurement technique to estimate fouling by blood proteins, for example. Another key element in the molecular shuttle design is the optimization of cargo loading onto the shuttles. Cargo is attached to microtubules via conventional bioconjugation techniques, for example utilizing the receptor-ligand pair streptavidin-biotin. We demonstrate that the speed of streptavidin-coated microtubules has to be optimized to facilitate attachment of biotinylated cargo. The biotin-streptavidin bond gains its ultimate strength on a timescale of milliseconds due to existence of metastable binding states. The modeling of the attachment and detachment processes reveal the “glue-like” behavior of biotin-streptavidin linkages. We finally discuss the successful integration of these design elements into the development of a smart dust biosensor. In this device, molecular shuttles capture antigens from the test solution, move until they bind fluorescent markers and accumulate at a distinct location for fluorescent read-out. It is envisioned that this autonomous microdevice can be manufactured in large numbers, stored in an inactivated state, reconstituted, distributed in an aqueous solution, activated by light and read out by stand-off fluorescence detection.
9:00 PM - TT5.22
Localised Surface Plasmon Resonance (LPSR) Initiated Polymerization within Self-assembled Monolayers on Nanostructured Metallic Thin Film.
Abdiaziz Farah 1 2 , Sheng Dai 2 , Juan pablo Bravo-Vasquez 2 , Jae-young Cho 2 , Hicham Fenniri 1 2 Show Abstract
1 Chemistry, University of alberta, Edmonton, Alberta, Canada, 2 , National Institute for Nanotechnology, Edmonton, Alberta, Canada
Novel surface initiated polymerization approach due to induction of heat dissipation emanating from localized surface plasmon resonance (LSPR) in thermally isolated nanostructured Au nanoislands using resonant laser light. Our approach is unique and has peculiar advantages over previously reported surface initiated polymerizations methods: it entails the fabrication of near-infrared-resonant nanoislands into a 2D thin film with interparticle junctions or hot spots that enhance only the SERS at near-infrared wavelengths. It is amenable to device integration process and use of chemically stable mercapto-styrenes with unique vibrational fingerprints and high conjugation character and therefore can be detected with high sensitivity and accuracy using surface enhanced Raman scattering (SERS).
9:00 PM - TT5.23
Diagnosing Lung Cancer in Exhaled Breath Using Gold Nanoparticles.
Hossam Haick 1 Show Abstract
1 Dept. Chemical Engineering, Technion - Israel Institute of Technology, Haifa Israel
Lung cancer is the leading cancer-related cause of death, accounting for 28 percent of cancer deaths and killing ~1.3 million people worldwide every year. Conventional diagnostic methods for lung cancer occasionally miss tumors and they are costly and unsuitable for widespread screening. Breath testing is a fast, non-invasive diagnostic method that links specific volatile organic compounds (VOCs) in exhaled breath to medical conditions. Studies of gas-chromatography/mass-spectroscopy (GC-MS) – primarily characterized by a detection limit of few parts-per-million (ppm) – linked with a pre-concentrator have shown that several VOCs in breath appear to be elevated in instances of lung cancer. The compounds of interest are generally to be found at 1-20 parts per billion (ppb) in healthy human breath, but can be seen in distinctive mixture compositions and at elevated levels from 10-100 ppb (picomolar-nanomolar concentrations) in the breath of diseased patients. Here, we report on a highly sensitive, stable, relatively inexpensive, and fast-response array of sensors based on gold (Au) nanoparticles (NPs), in conjugation with pattern recognition methods, that can distinguish between the breath of lung cancer patients and that of healthy controls, with no need for preconcentration of the lung cancer biomarkers in an atmosphere of high humidity. The organic functionalities were selected on the basis of our identification of 42 lung cancer biomarkers by GC-MS combined with solid phase microextraction (SPME). We selected five volatile biomarkers, which can be used to train and optimize the array of sensors, to simulate healthy breath and lung cancer breath.
9:00 PM - TT5.24
Structure and Properties of the Shell of the Hydrothermal Vent Limpet Lepetodrilus Cristatus.
Haimin Yao 1 , Christine Ortiz 1 Show Abstract
1 DMSE, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
Lepetodrilus cristatus are small (<10 mm) archeogastropod limpets commonly found at deep sea hydrothermal vent sites at enormous densities (2100 per dm^2) living on and around bacterial mats, where they may experience harsh physical and chemical environmental conditions including high and variable temperature fluctuations (1.5–60°C), high pressures (3 ×10^4 kPa), low and variable pH (2.8–8.), low and variable oxygen concentrations (0–110 μmol/L), normally toxic levels of sulfides and heavy metals, and various mechanical predatory attacks. Limpets adhere strongly to substrates using pedal mucus and a muscular foot, thereby protecting its interior vulnerable soft tissues with a calcified exterior cone-shaped, open-coiled shell. Scars reflective of shell damage repair and nonlethal attacks on Lepetodrilus are commonly observed in hot vent regions where potential predators such as zoarcid fish, galatheid crabs, and buccinid snails exist. In order to investigate the functional protection mechanisms of Lepetodrilus in surviving predatory attacks, the structure and properties of the shell of L. cristatus from the High Rise vent field on the Juan de Fuca Ridge, Northeast Pacific (2200 m depth) as investigated. Scanning electron microscopy (SEM) imaging revealed a multilayered structure composed of an outer proteinaceous periostracum (~2 μm thickness), followed by an inner aragonite-based, crossed-lamellar calcified layer bounded by narrow inner and outer prismatic layers(~70 μm thickness). Spatially-specific instrumented nanoindentation was employed quantify the local mechanical properties of the L. cristatus periostracum and aragonite-based shell and found to possess indentation stiffness values of approximately 8 and 70 GPa, respectively, and indentation hardness values of 0.2 and 2 GPa, respectively. Microhardness experiments at various loads (0.098 N, 0.49 N, 0.98 N) using a Vickers tip geometry were conducted and yielded microhardness values for the calcified shell ranging from 0.89 to 1.16 GPa. SEM imaging of the residual microhardness indents shows that the initiation of cracks in the calcified shell took place at the highest indentation load (0.98 N) and cracks were prone to propagate anisotropically parallel to the interlayer interfaces, thus avoiding the catastrophic fracture of the entire shell structure. The results reported may be able to provide improved guidelines for the design of human synthetic engineered protective defense applications.
9:00 PM - TT5.26
Proteins as Solid State Electronic Conductors.
David Cahen 1 , Izhar Ron 1 , Mordechai Sheves 1 , Israel Pecht 1 , Lior Sepunaru 1 Show Abstract
1 Materials and Interfaces, Weizmann Institute of Science, Rehovoth Israel
Electron transfer (ET) through proteins is a fundamental process in many biochemical reactions. The proteins’ chemical and structural design may thus hold information on the critical factors that make ET possible. Indeed, identifying such components in the protein structure is a major goal of ET studies of modified proteins in solution. We, and others showed that solid-state electron trans-port (ETp) studies are possible across non-modified proteins, between two solid electrodes, bio-molecular electronics. Most studies to date were conducted with a single or few molecules in the junction. Measuring an ensemble of molecules in a junction is not only a technological goal by itself, but may also avoid undesired effects intrinsic to working with nano-scale electrodes, and should improve measure-ment reliability, if samples can be prepared reproducibly. We succeeded to prepare and electrically characterize high quality, large area protein monolayer junctions on molecularly modified, oxidized Si with Bacteriorhodopsin (bR), a proton pumping membrane protein-chromophore complex, Azurin (Az), a type I blue-copper ET protein, and Bo-vine Serum Albumin (BSA). Based on the highly reproducible current-voltage (I-V) measure-ments we find clear differences between the different proteins in the junctions and small tunnel-ing decay constants for all the proteins that were studied, implying that inelastic hopping domi-nates transport. Such low values also reflect the ETp efficiency over long (10s of Å) distances in these proteins, when they serve as solid-state molecular bridges, as compared to analogous bridges of saturated organic molecules. The differences in ETp efficiency between the junctions can be understood in terms of the proteins’ secondary structure.We then put pour data in perspective by comparing them to all known protein ETp data in the literature. The remarkable conclusion is that proteins behave more akin to molecular wires than to insulators.* Work done. with Izhar Ron, Lior Sepunaru, Israel Pecht and Mordechai Sheves
9:00 PM - TT5.27
Nanocrystals for Medical Applications.
Zoraida Aguilar 1 , Hengyi Xu 1 , Ben Jones 1 , John Dixon 1 , Andrew Wang 1 Show Abstract
1 , Ocean NanoTech, LLC, Springdale, Arkansas, United States
Owing to the excellent optical and electronic properties of nanocrystals coupled with stability under relatively harsh environment, these have been targeted for various medical sensing applications. Medical sensing represents one of the nanotechnology applications that hold promise for commercial products1. Nanotech-derived products in the area of drug delivery was estimated at $290 million in 2005 and projected at $43 billion in 20102. Life sciences research will contribute $3.4 billion by 2010 with an annual growth rate at 30.3% while the National Science Foundation is predicting that the market for nanotechnology and corresponding products will reach $1 trillion in 10 to 15 years3-4. Biomedical applications require high-quality water-soluble nanocrystals. Quantum dots could be made directly in water but the resulting nanocrystals have narrow available size ranges with wide size distribution that causes wide FWHM. Quantum dots produced at high temperature organic solvent are monodisperse with narrow FWHM, very wide emission color ranging from ultraviolet to near infrared (300–2500 nm) by simply changing the size, omposition and/or structure. But, these quantum dots synthesized in organic solvents are insoluble in water. The same thing can be said for iron oxide magnetic nanoparticles. Using Ocean’s proprietary method, most hydrophobic, organic ligand-coated nanoparticles can be made soluble in water through the monolayer polymer coating strategy. This orients the carboxylic acid groups (or amine groups) on the outside converting the nanoparticles into water soluble (hydrophilic), bio-reactive, and stable particles against harsh conditions allowing bioconjugation. To take advantage of this market opportunity in nanotechnology, Ocean Nano Tech is pursuing the development of medical applications of our nanocrystals such as cancer cell detection, disease biomarker assays, drug delivery, MRI contrast imaging, etc. We will present our preliminary studies in the development of biosensors for early stage prion infection, cancer cell imaging, and disease biomarker detection. The nature of the nanocrystals used for these medical applications will be discussed.References1)Carbon Nanotubes Monthly, http://www.nanosprint.com/nanotubes/ newsletter/monthly0206/ application.html2)Drug delivery markets to get huge boost from Nanotechnology and MEMS, http://www.mediligence.com3)The U.S. Clinical Diagnostic Equipment Market, http://www.bccresearch.com/report/HLC032A.html.4)US Census Bureau, NHIS, CDC, NCHS, Boyle et al. Diabetes Care, Vol. 24, No.11, Nov. 2001.
9:00 PM - TT5.28
Kinetic, Au-Nano-Particle and Photoluminescence Study on the Reducing Ability of Medicinal Plant Extracts.
Shashi Kiran 1 , L. Souza 1 , Tarja Volotinen 2 , Lyubov Belova 2 , K. Rao 2 Show Abstract
1 Laboratory of Applied Biology, St Aloysius College, Mangalore India, 2 Group of Engineering Materials Physics, Dept. of Materials Science and Engineering, Royal Institute of Technology, Stockholm Sweden
Antioxidation, i.e. reducing, ability is one of the interesting properties of medicinal plant extracts used for various kinds of medicines and other medical applications. We report here results for three types (Andrographis paniculata, Vinca rosea and Stricnos nux-vomica.) of medical plants from Western Ghats of India, for which we have prepared a simple kinetic study on the gold nano-particle forming reaction by adding a few drops of aqueous hydrogen tetrachloroaureate solution (0.001 M) into 3 ml of the aqueous, diluted (1: 100 - 1000) plant extract solution, and measuring the excitation and emission photoluminescence spectra as a function of time. We have found that all three extracts show strong photoluminescence at 400 - 450 nm (exited at 305 nm) without the aureate addition. After the aureate addition, the original luminescence decreases and absorption, i.e. excitation, peak at around 550 nm increases both with a speed dependent on the plant. The peak at 550 nm indicates the forming of the nano-sized, reduced, metallic Au-particles. The material composition of the plant extracts and reduced particles have been analyzed by optical microscope, SEM, high resolution SEM and EDAX. The origin and the reason for the decrease of the original broad photoluminescence band are under investigation. The results of this study are aimed for a further study on the ability of plants to absorb and assimilate metals, which further would provide opportunities to utilize the plant extracts as nontoxic vehicles to stabilize nano-particles. We have compared the results with literature and found that the emission band around 400 - 450 nm, earlier attributed to the formed metallic Au nano-particles by Vilchis-Nestor et al (2008), is originated from the plant extracts in our case, not caused by the Au particles formed after the aureate addition. Our results for the absorption peak at 550 nm agree with the recent reports by Shankar et al (2004) and Ramezani et al (2008).
9:00 PM - TT5.29
Ultrahigh Sensitive Biomolecule Detection via Surface Enhanced Raman Scattering with Antireflective Silicon Nanotip Arrays.
Hung-Chun Lo 1 , Hsin-I Hsiung 4 , Chia-Fu Chen 2 , Jim Leu 1 , Kuei-Hsien Chen 3 , Li-Chyong Chen 4 Show Abstract
1 Insititute of Material Sciences and Engineering, National Chiao-Tung University, Taipei Taiwan, 4 Center for Condensed Matter Sciences, National Taiwan University, Taipei Taiwan, 2 Department of Materials Science and Engineering, Ming-Dao University, Changhua Taiwan, 3 Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei Taiwan
Nondestructive optical sensing of biomolecules with high sensitivity have been demonstrated using the template of silicon nanotips arrays (SiNTs) decorated with self assembled silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs). The presence of sub-10 nm noble metal particles with optimum separation from neighboring particles assures the ultrahigh sensitivity in biomolecule-detection via surface enhanced Raman scattering (SERS) techniques. In this work, the patented self masked dry etching technique was used to fabricate the SiNTs wafer with high curved surface area to achieve the excellent platform for noble metal nanoparticles formation and controlled-assembly. The nanostructured SERS-templates were comprised of arrays of nanotips with high aspect ratio, with apex and bottom diameter of ~2 nm and ~100 nm, respectively, height of ~1800 nm and number density as high as 10^11 cm^-2, which could enhance the real (exposed) surface area up to 500 times higher than the planar one with identical periphery. On the other hand, this novel SiNTs structure also supports the unique antireflection phenomena ensuring the laser light to be fully trapped to excite the target-analytes yielding profuse signals from targets. The superior nanostructures possessing the advantages of high surface area and antireflective nature have provide relatively high temporal stability of Raman signals to convince the ultra-sensitive, reliable and reproducible detection of biomolecules even after months’ storage under room temperature.
9:00 PM - TT5.3
Toward Generalized Simple Synthesis of Highly Crystalline Mesoporous Metal Oxides.
Youngjin Ye 1 , Easwaramoorthi Ramasamy 1 , Ulrich Wiesner 2 , Francis DiSalvo 3 , Jinwoo Lee 1 Show Abstract
1 Chemical Engineering, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea (the Republic of), 2 Materials science and engineering, Cornell University, Ithaca, New York, United States, 3 Chemistry and Chemical Biology, Cornell University, Ithaca, New York, United States
Controlling the morphology of TiO2 is crucial for the development of enhanced dye-sensitized solar cells (DSSC). In particular, high crystalline mesoporous TiO2 has much potential for application in DSSC due to its high surface area and electronic structures. Despite noticeable progress in the synthesis of mesoporous transition-metal oxide, the direct synthesis of highly crystalline mesoporous transition-metal oxide is a still challenge. Although mesoporous materials have been synthesized by soft- and hard-templating methods, poor crystallinity and tedious steps still remain as major problems. Here we present one-pot synthesis of highly crystalline and thermally stable mesoporous TiO2 by sol-gel based synthesis which combines amphiphilic diblock copolymer, poly(isoprene-block-ethylene oxide), and sol of titania precursors, and aluminosilicate, for application in DSSC. The structure of mesoporous TiO2 synthesized by this method remains without pore collapse, even after heat treatment of 700°C. DSSC is fabricated with using this material, and its I-V characteristics would be also presented. This simple process can be easily extended to other mesoporous crystalline metal oxide system.
9:00 PM - TT5.4
Block Copolymer Directed `One-Pot’ Simple Synthesis of L10 Phase FePt Nanoparticles inside Cellular Ordered Mesopores.
Eunae Kang 1 , Jin Kon Kim 1 , Jongmin Shim 1 , Ulrich Wiesner 2 , Jinwoo Lee 1 Show Abstract
1 chemical engineering, Pohang university of science and technology, Pohang Korea (the Republic of), 2 Materials Science and Engineering, Cornell University, Ithaca, New York, United States
Ordered assembly of FePt nanocrystals is of great importance for magnetic data storage media. Tetragonal (fct) structured FePt is known to have large uniaxial magnetocrystalline anisotropy and high coercivity, which is ideal for magnetic storage media. Chemical routes were frequently employed to synthesize monodisperse FePt nanocrystals. Chemical synthesis at low temperature typically produces superparamagnetic cubic FePt nanocrystals. The chemically synthesized FePt nanocrystals have to be heat-treated to 550 oC or more to obtain fct phase (the so-called L10 structure) FePt. However, the surfactants coating the particles are decomposed at these temperatures, leading to agglomeration of monodisperse nanoparticles. The resulting structure is not useful for high-density recording media. In this context, it is demanded to develop fct L10 phase nanocrystals without agglomeration. Herein, we report on simple ‘one-pot’ synthetic method of size controlled L10 phase FePt nanoparticles employing poly(isoprene-block-ethylene oxide) PI-b-PEO diblock copolymers. Synthesis was achieved by the assembly of PI-b-PEO block copolymers with aluminosilicate sols, iron precursor, and platinum precursor. The as-synthesized material was heat treated to 800 oC using 1oC/min ramp under argon/H2 mixture gas and held for 2 hours or more resulting in fct FePt nanocrystals encapsulated in ordered cellular mesopores. The X-ray diffraction patterns show that all FePt nanoparticles have typical patterns of face-centered tetragonal structures (Figure 1a). The broadness change of (111) peak indicates that the higher loading precursor generated larger sized fct FePt particles. Transmission electron micrographs show the ordered cellular structure of as-synthesized structure is preserved after heat-treatment at 800 oC, thereby presenting thermal stability of PI-b-PEO direct mesoporous aluminosilicates. One or more FePt particles are located inside one cellular pore and FePt particles are homogeneously dispersed all over the pores without any agglomeration. As-expected, the FePt nanoparticles show ferromagnetic behavior at room temperature.
9:00 PM - TT5.6
Surface Modification for Strongly Charged Quantum Dots and its Application to Bioconjugation and Layer-by-layer Assembly.
Ho Jin 1 , Jutaek Nam 1 , Joonhyuck Park 2 , Sungho Jung 1 , Sungjee Kim 1 2 Show Abstract
1 Chemistry, POSTECH, Pohang, Gyeongbuk, Korea (the Republic of), 2 School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang, Gyeongbuk, Korea (the Republic of)
Semiconductor quantum dots can have distinct advantages over traditional fluorescent organic dyes because they show robustness against photo-bleaching, narrow emission profiles, large extinction coefficients, and multiplexing capability by single excitation. Highly crystalline and bright quantum dots are typically obtained in hydrophobic solutions by solvothermal method. For biological applications, it is very important to guarantee colloidal stability of quantum dots in physiological environments. Conventional water-soluble quantum dots have the terminal functional groups of carboxylic acids or primary amines. They can provide conjugation sites as well as dispersion properties. However, their colloidal stability is limited to a pH region determined by the pKa values. This may limit the applications of quantum dots in use of wide pH ranges for conjugations or self-assemblies. We report new surface ligands for quantum dots that have strongly charged functional groups by sulfonate or quaternary ammonium that can retain charges irregardless of the pH. Quantum dots that are surface modified with the strongly charged ligands can show excellent colloidal stability in pH 3 to 12 and in high salt conditions. We introduce mixed surface ligand system to quantum dots that consists of carboxylic acid and sulfonate functional groups. The mixed ligand system can be used for carbodiimide bioconjugation without any aggregations. In addition, we demonstrate layer-by-layer assemblies by alternatively introducing the strongly negatively charged and positively charged quantum dots to a substrate. We observe linear deposition of the quantum dot layers by repeated dipping processes.
9:00 PM - TT5.7
One-pot Multi Catalyst System using Fe3O4 Magnetic Nanoparticles and Oxidases as a Colorimetric Sensor.
Jong Min Shim 1 , Moon-Il Kim 2 , Hyun Gyu Park 2 , Jinwoo Lee 1 Show Abstract
1 Chemical Engineering, Pohang university of science and technology, Pohang Korea (the Republic of), 2 Chemical & Biomolecular Engineering, KAIST , Daejeon Korea (the Republic of)
Recently, inorganic Fe3O4 magnetic nanoparticles (MNPs) have attracted much attention due to their extra-ordinary peroxidase mimicking activity. For efficient applications using MNPs as an artificial enzyme of peroxidase, it is highly desirable to develop nano-scales system that enable high activity and stability, and accessibility with another catalyst like enzymes, as well as easy separation and reuse. Herein, one-pot multi-catalyst system, so called “nanofactory”, is developed entrapping MNPs and oxidases in mesoporous silica with high loading simultaneously above 40 wt% MNPs and 20 wt% enzyme. As low as 50 nM H2O2 could be detected with a linear range from 0.1 μM to 10 μM via our system. To apply this system to detect clinically important substrates, glucose oxidase and cholesterol oxidase were incorporated in the remaining volume of the mesopore of nanofactory. About 3 μM glucose and 5 μM cholesterol could be detected via our system. Our approach provided highly loaded MNP system and any highly loaded enzymes with superior activity, stability, and reusability, thereby making further applications as versatile sensors for detecting DNA, protein, and cell highly promising.
9:00 PM - TT5.8
Local Temperature Measurement of Quantum Dots Conjugated Iron oxide Nanoparticles.
Shujuan Huang 1 , Amit Gupta 2 , Diana-Andra Borca-Tasciuc 1 Show Abstract
1 Department of Mehcanical, Aerospace, Nuclear Engineering, Rensselaer Polytechnic Institute, Troy, New York, United States, 2 Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, United States
Within the last decade, several experimental studies have showed that in the presence of alternating electromagnetic field, biomolecules attached to nanoparticles experience changes that is believed to be due to thermal effects associated with nanoparticle heating. However, predictions of the temperature rise employing classical heat generation and heat transfer laws indicate that significant heating from an individual nanoparticle is not possible. Hence it is of high interest to measure the local temperature in the vicinity of remotely heated nanoparticles. In this work, the temperature in the vicinity (~ 3.6 nm) of heated iron oxide nanoparticles is measured using fluorescent CdSe quantum dots (QD) as temperature probes. Two systems are studied. In the first system, used as a control sample, carboxyl terminated QD and amine functionalized nanoparticles are mixed together. When the electromagnetic field is applied, QD measure an average temperature rise, since they are free to move within the solution. In the second system QD are conjugated to nanoparticles via standard EDC reaction chemistry. Here, QD remain in the vicinity of nanoparticles, measuring a local temperature rise. Preliminary results show negligible difference in the temperature of the quantum dots in mixed and respectively conjugated systems, supporting the predictions of heat transfer theory.
Stefan Maier Imperial College London
Ulrich Wiesner Cornell University
Jinwoo Lee Pohang University of Science and Technology
TT6: Functional Nanoparticles II
Tuesday AM, December 01, 2009
9:15 AM - TT6.1
Semiconductor Quantum Dots for Cell Imaging.
Zoraida Aguilar 1 , Hengyi Xu 1 , Ben Jones 1 , John Dixon 1 , Andrew Wang 1 Show Abstract
1 , Ocean NanoTech, Springdale, Arkansas, United States
Nanotechnology is currently undergoing unprecedented development in various fields. There has been a widespread interest in the application of nanomaterials in medicine with its promise of improving imaging, diagnostics, and therapy. The recent advances in engineering and technology have led to the development of new nanoscale platforms such as quantum dots, gold nanocrystals, superparamagnetic nanocrystals, and other semiconductor nanoparticles. Literature on the applications of quantum dots in life sciences has recently increased in number. This may be have led to predictions that nanotechnology in life sciences research will contribute $3.4 billion by 2010 while the National Science Foundation is predicting that the market for nanotechnology and corresponding products will reach $1 trillion in 10 to 15 years. Ocean’s high quantum-yield quantum dots (QDs) is currently being used for cell imaging, as wells as for the detection of proteins, DNA, whole cells, and whole organisms. Imaging involves conjugation of QDs to a highly sensitive and specific antibody to form QD~Ab conjugate that attaches to a specific protein target on the surface of the cell. Attachment of the QD~Ab on the cell surface allows the imaging of the cell under a fluorescence microscope. This system can be used in a multiplex immunoassay detection of several types of cells (or microorganisms) in a single sample when several size tunable quantum dots are used as reporter probes.We report the QDs imaging of breast cancer cells. Using the breast cancer cell line SK-BR3 which expresses high levels of EpCAM antigens on the cell surface, anti-EpCAM were conjugated Ocean’s QSH620. To eliminate non specific binding of the QD~Ab Ocean’s super blocking buffer BBB and BBG were used. Preliminary results of parameter studies will be discussed.
9:30 AM - TT6.2
Aqueous Synthesis of Near-Infrared Quantum Dots.
Wei-Heng Shih 1 , Ian McDonald 1 , Yu-Chieh Lu 1 3 , Hui Li 1 , Wan Shih 2 Show Abstract
1 Department of Materials Science & Engineering, Drexel University, Philadelphia, Pennsylvania, United States, 3 Department of Chemical Engineering, National Tsing Hua University, Hsinchu Taiwan, 2 School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, Pennsylvania, United States
Quantum Dots (QDs) are semiconducting nanocrystals that have photoluminescent (PL) properties brighter than fluorescent molecules and do not photo bleach, ideal for in vivo imaging of diseased tissues or monitor biological processes. Near-infrared (NIR) fluorescent light within the window (700-1000 nm), separated from the major absorption peaks of hemoglobin and water, has the potential to be detected deeper than several mm under the surface. Previously, we have developed CdS QDs using the aqueous approach. Here we present an aqueous approach for Cd1-xPbxS QDs that has NIR emission between 800 to 950 nm for x>0.5. The NIR QDs can be further stabilized by replacing the capping molecules. References H. Li, W. Y. Shih, and W.-H. Shih, “Synthesis and Characterization of Biocompatible Aqueous Carboxyl-capped CdS Quantum Dots,” Ind. & Eng. Chem. Res., 46, 2013-2019 (2007)
9:45 AM - TT6.3
Lithographic Coloring of Magnetic Photonic Crystal Microspheres : Multiple Nanostructured Domains in a Single Microsphere.
Junhoi Kim 1 , Jianping Ge 2 , Hyoki Kim 1 , Howon Lee 1 , Yadong Yin 2 , Sunghoon Kwon 1 Show Abstract
1 , Seoul National University, Seoul Korea (the Republic of), 2 Department of Chemistry, University of California, Riverside, Riverside, California, United States
We report lithographically colored magnetic photonic crystal microspheres fabricated by the combination of the bottom-up based magnetic self-assembly and top-down based lithographic fixation of its assembled photonic nanostructure by UV-radiated polymerization. We have fabricated a variety of complex photonic crystal microspheres having heterogeneous and anisotropic optical properties, which cannot be synthesized by conventional wet chemical synthesis methods governed by energy minimization nature.Our material used as a precursor for generating photonic crystal microspheres is a composite of inorganic superparamagnetic colloidal particles dispersed in organic photocurable resin. The precursor is immiscible to form emulsion droplets in a mineral oil. Superparamagnetic colloidal particles in emulsion droplet are self-assembled into one-dimensional chains under the external magnetic field, and whose interparticle distance is determined by balance of magnetic dipolar attraction force and repulsive forces owing to the surface charge and overlap of solvation layers in solvents. The chain-like structure of arranged superparamagnetic colloidal particles diffracts visible light, whose wavelengths are determined by varying strength or the direction of the magnetic field. Superparamagnetic colloidal particles have inherent merits of high magnetization, strong repulsion, and no hysteresis, thus enable fast tuning covering entire visible spectrum. The assembled chain structures in the emersion droplets can be fixed locally by the partial polymerization of the photocurable resin. Patterned UV can be exposed to the emulsion droplet by spatially selective illumination of UV using spatial light modulator. By virtue of high resolution of micromirror arrays as a spatial light modulator, the shape and the size of UV illumination pattern can be modulated with the resolution of a few micrometers.Multicolored photonic crystal microspheres can be produced by repetition of the tuning magnetic field and the modulating UV illumination pattern. Each part of a photonic crystal ball shows distinct optical characteristics within a single photonic crystal ball since the arrangements of nanoscale colloidal building blocks in the ball are different. In particular, the fabricated multicolored photonic crystal microspheres have multiple reflection peaks in their reflection spectra from individual photonic crystal balls, which show potential use for multiplexed-encoded particles. The heterogeneous and anisotropic optical characteristics of multicolored photonic crystal balls also enable magnetic tuning of optical properties based on the orientation of balls.We believe that lithographically colored magnetic photonic crystal microspheres are suitable for various applications such as multiplexed-encoded particles for biochemical assay applications.
10:00 AM - **TT6.4
Design of SERS-Active Particles and Assays That Use Them.
Michael Natan 1 Show Abstract
1 , Oxonica Materials Inc., Mountain View, California, United States
There is an increasing need for analytical measurements that can be carried out at the point of use, whether for homeland security, food contamination, or anti-counterfeiting applications. We have developed a series of SERS-active nanoparticles, and several different assay formats, that are designed to be used with small or handheld Raman readers. Some of these particles are encapsulated SERS-active labels (SERS nanotags) that allow indirect detection/quantitation; others are based directly on the SERS activity of the analyte. We will describe recent results from applications designed for use with handheld readers that leverage three different assay formats (“lateral flow”, “magnetic particle”, and “direct colloid”). Each of these formats is applicable to large molecules (e.g. proteins) or small molecules (e.g. melamine), and offers a combination of unmatched speed and sensitivity.
10:30 AM - TT6.5
Nanoparticle Assembly via Bifunctional Genetically Engineered Peptides for Inorganics.
Turgay Kacar 1 2 , Mustafa Gungormus 1 , Yuhei Hayamizu 1 , Ersin Emre Oren 1 , John Evans 3 , Candan Tamerler 1 2 , Mehmet Sarikaya 1 Show Abstract
1 Materials Science and Engineering, University of Washington, Seattle, Washington, United States, 2 Molecular Biology and Genetics, Istanbul Technical University, Maslak - Istanbul Turkey, 3 Laboratory for Chemical Physics, New York University , New York, New York, United States
Genetically engineered peptides for inorganics (GEPIs), isolated through biocombinatorial approaches utilizing, e.g., phage display and cell surface display peptide libraries, were used for metal and metal oxide nanoparticle immobilization on inorganic surfaces. In this work, following successful quantitative molecular binding characterization, using fluorescence microscopy, surface plasmon resonance spectroscopy, and/or atomic force microscopy techniques, gold and silica nanoparticle immobilization on metal and oxide surfaces was achieved using bifunctional GEPIs (bi-GEPIs) as linker. Specifically, gold binding peptide (AuBP) and quartz binding peptide (QBP) sequences were chemically linked through either flexible (-GGG-) or rigid (-PPP-) amino acid triplets, constituting bi-GEPIs. Subsequently, silica or gold nanoparticle assembly was successfully carried out on gold and glass surfaces that were functionalized with bifunctional peptides, respectively. Following nanoparticle attachment, the substrates were characterized by atomic force microscopy and dark-field (DF) imaging. Adsorption of each bifunctional peptide onto gold as well as onto silica was studied by surface plasmon resonance (SPR) spectroscopy using a modified approach to obtain quantitative kinetics. Although synthetic chemical reagents such as alkanethiols, aminoalkylalkoxysilanes, etc., are mostly used in the literature as linkers for covalent attachment of the nanoparticle to inorganic surfaces, our results demonstrate that bi-GEPIs can be an attractive alternative approach for the immobilization of nano-metallic and -oxide particles on any given solid substrate provided that the appropriate solid-specific peptide is used in the bifunctional entity. The novel molecular bi-GEPI platform has enormous potential in practical application sin nanobiotechnology, e.g., in functionalization of core-nanoshell particles, core-satellite nanoparticle systems, immobilization of nanoparticles on substrates and on biomacromolecules towards functional utilization. The research was supported by Genetically Engineered Materials Science and Engineering Center (GEMSEC), an NSF-MRSEC at UW.
10:45 AM - TT6.6
DNA Assisted Energy Transfer and Design of White Luminescent Nanofibers.
Yogesh Ner 1 2 , Daminda Navarathne 1 2 , Jeffrey Stuart 2 , James Grote 3 , Gregory Sotzing 1 2 Show Abstract
1 Polymer Program, Univ. of Connecticut, Storrs, Connecticut, United States, 2 Department of Chemistry, Univ. of Connecticut, Storrs, Connecticut, United States, 3 , US Air Force Research Laboratory, Wright-Patterson Air Force Base, Ohio, United States
Herein, we report the fabrication of DNA based white light luminescent nanofibers by taking advantage of the ability of DNA to interact with cationic surfactants and fluorophores. Specifically, we have encapsulated multiple chromophores in DNA matrix which can be spatially organized using DNA’s double helical structure. Such hierarchical organization provides basis for efficient energy transfer. We have furthermore developed strategy to fabricate DNA nanofibers, by complexion it with cationic surfactant and using the electrospinning technique. The complexes of DNA exhibit great improvement in processability by rendering them organic soluble which can be easily electrospun into uniform nanofibers. The DNA complexes in solid state also exhibit highly ordered mesoscopic structure. Such regular orthogonal arrangement along with the binding ability of DNA with small molecules via intercalation, minor and major groove binding, and association with the surfactant component through entrapment provides an opportunity for the spatial organization of multiple dyes. We have explored this feature and encapsulated donor: acceptor dyes which can bind DNA by different mechanisms which led to efficient energy transfer even at very low loading of the acceptor dye (D:A = 200:1). Moreover, DNA-CTMA nanofibers also exhibit significant enhancement in fluorescence yield, (100X), mainly attributed to high surface area, confined geometry, and chromophore intercalation when compared to similar dye doped compositions based on PMMA films. DNA plays major role in both fluorescence enhancement and efficient energy transfer. The color emission from these nanofibers is a result of fluorescence resonance energy transfer (FRET) based simultaneous emission from donor and acceptor dyes which can be controlled by varying their ratio and/or changing dye composition. Using this strategy, we further demonstrate pure white light emission from nanofibers by rationally choosing a donor-acceptor pair and controlling their ratio. We have demonstrated white light emission from these nanofibers when coated on commercially available UV LEDs. This important advance in biological nanofibers may be useful in applications areas such as sensors, nanometric light sources, subwavelength optical waveguides, lasing materials and solar cells.
TT7: Biomedical Nanoscience
Tuesday AM, December 01, 2009
11:30 AM - **TT7.1
Nanoscale Biomedical Plasmonics: Multimodality Theranostic Complexes and Light-controlled Gene Delivery.
Naomi Halas 1 Show Abstract
1 ECE Dept.- MS-366, Rice University, Houston, Texas, United States
Near infrared plasmon-resonant nanoparticles have been shown to be central to many useful and highly promising applications in biomedicine, from contrast agents in bioimaging, to photothermal therapeutics, to drug delivery. We have recently shown that near IR resonant nanoshells can be used to enhance the fluorescence of the weak fluorophore indocyanine green (ICG), increasing its quantum efficiency from below 10% to greater than 80%. Multimodal contrast agents combining this enhanced NIR fluorescence capability can be combined with a photothermal therapeutic response. Alternatively, this multifunctional platform can be modified to serve as a nonviral vector for light-controlled gene delivery within cells. We will discuss the basic physical properties of these nanoscale complexes in terms of the requirements for their corresponding specific biomedical applications.
12:00 PM - TT7.2
Nano/Meso/Microspheres for Intratumoral Chemotherapy of Lung Cancer.
Eugene Goldberg 1 , Firuz Celikoglu 2 , Seyhan Celikoglu 2 Show Abstract
1 Materials Science & Engineering, University of Florida, Gainesville, Florida, United States, 2 , University of Istanbul, Istanbul Turkey
Systemic drug toxicity severely limits the effectiveness of conventional chemotherapy. In spite of significant advances in cancer diagnosis and treatment, the CDC has reported a 75% increase in lung cancer mortality during the past 20 years. There is clearly a need for new therapeutic concepts which prolong survival, improve patient quality of life, and are clinically practical and cost effective. Reported here is the development of a new treatment paradigm for lung cancer; endobronchial intratumoral chemotherapy (EITC). The scope of this research has embraced (1) the synthesis of cancer drug loaded albumin (BSA) nano-meso-microspheres (MS) designed to prolong intratumoral (IT) drug delivery, (2) preclinical animal evaluation, and (3) clinical studies in non-small cell lung (NSCL) cancer patients. MS drug loading, ease of aqueous dispersion for injection, and drug release by diffusion and bio- degradation were designed for IT chemotherapy. Initial studies compared conventional IV delivery of the cancer drug, mitoxantrone (MXN), in a metastatic murine Lewis lung carcinoma and 16C mammary adenocarcinoma. Multiple IT injections of aqueous MXN-BSA-MS dispersions with drug dosage of 24-48 mg/kg were tested. Free drug given IT was much more effective and much less toxic than IV delivery and achieved 40-60% prolonged survival. However, IT injection of MXN-BSA-MS at doses of 32-48 mg/kg achieved 80% tumor-free survival for more 5 times longer than control survival without toxic effects. Lung cancer clinical studies were conducted in collaboration with Dr. S. Celikoglu at the University of Istanbul Medical Center. Patients presenting with NSCLC, often with severe bronchial obstruction, were treated with multiple IT injections of cisplatin or MXN through a needle-equipped bronchoscope in weekly sessions for up to 3 weeks as needed. Necrotic tumor tissue was removed by dissection and aspiration. Such patients respond poorly to conventional chemotherapy and are often inoperable. In most cases there was rapid relief of breathing difficulties and collapsed lungs after 1-2 IT treatment sessions. For almost all patients (~500 to date) bronchoscopic IT treatment enabled further treatment by brachytherapy and/or surgery. Thus, EITC was shown to be a clinically practical and patient friendly new procedure with none of the toxic complications associated with IV chemotherapy. In the current phase of clinical studies, EITC treatment is being investigated with cisplatin and mitoxantrone loaded BSA-MS for prolonged and more effective IT lung cancer therapy.
12:15 PM - TT7.3
Inducing Apoptosis of Brain Tumor Cells by Using Multifunctional Nanoparticle-based Targeted Drug Delivery.
KiBum Lee 1 , Jongjin Jung 1 , Prasad Subramaniam 1 , Vladimir Lokshin 1 , Kevin Memoli 1 , Aniruddh Solanki 1 Show Abstract
1 Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States
This talk will focus on developing methods for synthesizing multi-functional nanoparticles (i.e. dual-mode imaging agents and target-specific drug delivery vehicles) and utilizing the functional nanomaterials as chemotherapeutic agents against brain tumor cells [glioblastoma multiforme (GBM)] in a highly selective and sensitive way. Nanostructures and nanomaterials can interact with biological systems at the molecular level with high specificity and sensitivity. Such unique properties of nanomaterials endow the nanoparticle-based drug delivery systems with the capability to regulate and interact with biological targets (e.g. proteins and cells) in controlled manner for inducing the desired physiological responses. The unique physical properties of these nanomaterials are critical for probing biomolecular interactions. In our experiments, we typically synthesize inorganic nanoparticles such as gold nanoparticles, quantum dots, lanthanide-doped nanoparticles, and magnetic nanoparticles that are readily tuned and possess novel electronic, optical, magnetic, and structural properties. These unique attributes make these nanoparticles useful as nanocarriers for chemotherapeutic molecules, as they can be used to deliver drugs and simultaneously monitor the drug delivery over extended periods of time in vitro and in vivo. As a model study incorporating a nanoparticle-based drug delivery system into targeting brain cancer, we used several glioblastoma cell lines including the wild-type U87, U87-EGFP, and U87-EGFRvIII. In these projects, we carefully design the ligand/conjugation chemistry to make these nanoparticles biocompatible. We have developed novel approaches for targeting anti-cancer drugs [e.g. Receptor tyrosine kinase inhibitor (Erlotinib) and Histone deacetylase (HDAC) inhibitors] and modified siRNA (against EGFRvIII receptors) conjugating them with nanoparticles. In addition, the cytotoxicity of nanoparticles, which could be a possible limitation for the application of nanoparticles as molecular probes and drug delivery systems, was studied using our glioblastoma cellular assays. In summary, we are working on two orthogonal nanotechnology-based approaches: i) application of multi-functional nanoparticles for non-viral siRNA delivery in GBM cell lines to manipulate gene expression levels of GBM cell proliferation; and ii) harnessing the potential of the multivalent nanoparticles for delivering anti-cancer therapeutics into the glioblastoma cell lines with high efficacy. A summary of the results from these efforts and future directions will be discussed in this talk.
12:30 PM - TT7.4
PEG-Stabilized Drug-Albumin Dispersions for Control of Particle Size in the Synthesis of Nano-Mesospheres Designed for Intratumoral Cancer Chemotherapy.
Hung-Yen Lee 1 , Eugene Goldberg 1 Show Abstract
1 Materials Science & Engineering, University of Florida, Gainesville, Florida, United States
Intratumoral (IT) chemotherapy using cancer drug loaded albumin (BSA) nano-mesospheres (MS) has become a promising new approach to localized cancer therapy, especially for non-small cell lung cancer (NSCLC). IT drug delivery via bronchoscopic injection can achieve an IT drug superdose and nano-mesosphere compositions afford good permeation of the tumor tissue with prolonged local drug activity via drug diffusion and MS biodegradation. Control of MS particle size and size distribution is important to the preparation of drug-MS compositions. Good dispersion of MS compositions in saline is also important for effective IT injection. Reported here is the use of 2000D poly(ethylene glycol) (PEG) to facilitate control of particle size in the synthesis of mitoxantrone (MXN)- BSA MS. A water-in-oil dispersion system similar to w/o emulsions but with a polymeric steric stabilizer in the oil phase (i.e. Poly- (cellulose acetate butyrate) was mmodified with PEG in the water phase to achieve particle size control and achieve narrow size distributions in the nano-meso particle size range (0.1-10um). By this procedure, various nano-meso MS based on MXN and BSA were readily prepared for IT chemo-therapy studies. PEG associate with these MS preparations also enhanced the dispersibility for IT injection.
12:45 PM - TT7.5
pH-Induced Aggregation of Gold Nanoparticles for Photothermal Cancer Therapy.
Ju Taek Nam 1 , Nayoun Won 1 , Ho Jin 1 , Hyokyun Chung 1 , Sungjee Kim 1 Show Abstract
1 chemistry, POSTECH, Namgu, Pohang Korea (the Republic of)
Noble metal nanostructures can be ideal candidates for photothermal cancer therapy by their large light extinctions at surface plasmon resonances and the efficient heat conversions. Various gold nanostructures that can absorb near-infrared (NIR) have been demonstrated for photothermal effect including nanorods, nanoshells, and nanocages. However, before metal nanostructures can be clinically tested for photothermal cancer therapy, they should expect reasonably fast clearance through urinal pathways. The previously reported metal nanostructures have large hydrodynamic sizes reaching ~100 nm, as a result to exploit NIR wavelengths for deep tissue penetrations. Herein, we report a new photothermal therapy concept using ‘smart’ gold nanoparticles that exploit coupled surface plasmon modes of nanoparticle aggregates. ‘Smart’ gold nanoparticles consist of 10 nm gold spheres made by conventional citrate reduction method and surface molecules that can convert their charges from negative to positive under mild acidic environment. ‘Smart’ gold nanoparticles are designed to form aggregates in intracellular environment. With the relatively small size of 10 nm, ‘smart’ gold nanoparticles can be efficiently internalized into cancerous cells. Triggered by the pH change, the nanoparticle surfaces are engineered to have both positive and negative charges by the partial charge conversion of the surface molecules. Electrostatic attractions between the nanoparticles rapidly form aggregates inside cells, and the aggregates accumulate as the exocytosis is blocked by the increased size. Endocytosis of gold nanoparticles and the aggregation is monitored real-time by dark field optical microscopy. The pH-induced formation of aggregates shifts the absorption to far-red and NIR. This shift can be used for selective and deep disuse penetrating photothermal therapy. ‘Smart’ gold nanoparticle shows selective and efficient destruction of cancerous cells by the turn-on mechanism with the intensity threshold 5 W/cm2 to induce the thermal destruction. In the intensity range of 5–13 W/cm2, the circular area of damaged cells increases linearly with the irradiation power density.
TT8: Applied Bionanosystems II
Tuesday PM, December 01, 2009
2:30 PM - TT8.1
A UHV STM Study of Molecular Association and Surface Composition in the Pharmaceutical Carbamazepine.
Erin Iski 1 , Ashleigh Baber 1 , Heather Tierney 1 , April Jewell 1 , Andrew Urquhart 2 , Alastair Florence 2 , Blair Johnston 2 , E. Charles Sykes 1 Show Abstract
1 Chemistry, Tufts University, Medford, Massachusetts, United States, 2 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow , Scotland, United Kingdom
Non-covalent intermolecular interactions are of significant interest in understanding the properties and structure of pharmaceuticals. Their influence ranges from solid-state structure, directing 3D packing in polymorphs for example, to drug-drug, drug-excipient, and drug-materials interactions during formulation and manufacture. Surface characterization is also of interest in detailing the potential impact that drug-surface interactions may have on the outcome of crystallization processes. Carbamazepine (CBZ) is a dibenzazepine drug widely used in the treatment of epilepsy and, although it has been heavily studied in the solid-state, the intermolecular packing interactions on a 2D scale have not received significant attention. We present results from an ultra-high vacuum scanning tunneling microscopy (UHV STM) study of 2D packing arrangements of CBZ on both Au(111) and Cu(111) surfaces at 78 K. A range of surface coverages and annealing temperatures were studied. On both of the surfaces, the molecules assembled as hydrogen bonded trimers, a packing arrangement that has not previously been observed in 3D structures of this compound. The investigation also revealed that the molecule has a substantially different packing density on the two surfaces with the molecule packed more tightly on the Cu surface. The observations raise the possibility of using molecular packing templates, formed by manipulating substrate-molecule interactions on different substrate surfaces, to template or control polymorphism. Theoretical modeling was also used to examine the packing structures and hydrogen bonding possibilities.
2:45 PM - TT8.2
Long-Circulating Mesoporous Silica Microparticles for Biomedical Applications: Delivery of Therapeutic Agents and MRI Contrast Agents.
Jeremy Steinbacher 1 , Christopher Landry 1 Show Abstract
1 Chemistry, University of Vermont, Burlington, Vermont, United States
The use of particles in biomedical applications has attracted increasing interest in recent years due to the possibility of selectively delivering therapeutic or imaging agents to specific cells within the body, obviating the need for systemic doses of potentially harmful agents. Nanoparticles have received a large share of the research focus; however, questions remain as to the in vivo toxicity of many nanoparticle formulations. In addition, many nanoparticles are transported to lysosomes when taken up by cells, leading to their decomposition and the destruction of their molecular cargoes by enzymatic action within the lysosome. As an alternative, we have developed a synthesis of acid-prepared mesoporous silica (APMS) microparticles. These particles exhibit the large surface and pore volume associated with mesoporous solids but have pore diameters and particle diameters that can be synthetically controlled. More importantly, amorphous silica is inherently non-toxic and can be easily functionalized by well-established methods. The functional groups on the exterior particle surface and interior pore surface can be modified separately to control the cell uptake characteristics and therapeutic loading characteristics, respectively. APMS externally modified with tetraethylene glycol chains [APMS-(s)TEG] are avidly taken up by murine lung and human malignant mesothelioma (MM) cells with minimal toxicity even at high doses. Importantly, APMS are not membrane-bound after endocytosis allowing therapeutic cargos to be released directly to the cytosol. Indeed, the chemotherapeutic agent doxorubicin can be adsorbed to the pore surfaces of APMS-(s)TEG and delivered to tumor cells, and we have shown that in vitro, doxorubicin-loaded particles are roughly 80-fold more effective at killing MM cells than doxorubicin alone. In an in vivo mouse tumor xenograft model, doxorubicin-loaded particles were at least as effective as free doxorubicin in reducing tumor volume. Finally, we have attached a ligand for gadolinium to the pore surfaces of APMS-(s)TEG for use as nuclear magnetic resonance imaging (MRI) contrast agents. In vivo MRI studies have shown that APMS/Gd are effective contrast agents when administered by several methods. Interestingly, microparticles administered by intraperitoneal injection were excreted through the bladder, and the particles circulated in the vasculature when administered via intravenous injection for at least four hours. Studies are currently underway to elucidate how APMS-Gd-(s)TEG enter the bladder and the mechanisms that allow long-circulation in the vasculature. We note that the health of the animals was not impacted by small or large (up to 500 mg/kg) doses of APMS and suggest that APMS are a promising microparticle system for the delivery of a variety of therapeutic and imaging agents.
3:00 PM - TT8.3
Mimicry of Natural Structural Colors.
Mathias Kolle 1 2 , Maik Scherer 1 , Heather Whitney 3 , Ullrich Steiner 1 2 Show Abstract
1 Cavendish Laboratories, University of Cambridge, Cambridge United Kingdom, 2 Nanoscience Centre , University of Cambridge, Cambridge United Kingdom, 3 School of Biological Sciences, University of Bristol, Bristol United Kingdom
In nature, intense and distinctive colors play an important role in intra- and inter-species communication. The most impressive natural colors arise from micrometer- to nanometer-sized structures, which often consist of intrinsically transparent materials. The underlying physical principles that create such structure based colors are well understood. The challenge lies in applying them to create functional replicas of natural photonic structures. We aim to create coatings based on nature-similar structures that optimally exploit different optical effects such as multilayer interference, diffraction from lateral structures as well as fluorescence. Efficient, simple procedures such as nanoimprinting or nanosphere-lithography and a variety of polymers and inorganic materials are used and will be subject of this presentation. In addition, we demonstrate a stretch-tuneable structural coating that promises a wide range of industrial applications such as tuneable filters, optical stress and strain sensors or unique labels in security applications.
3:15 PM - TT8.4
Sequencing DNA using a Nanopore in a Solid State Membrane.
Deqiang Wang 1 , Utkur Mirsaidov 1 , Valentin Dimitrov 1 , Jeff Comer 1 , Winston Timp 2 , Aleksei Aksimentiev 1 , Gregory Timp 1 Show Abstract
1 Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, 2 School of Medicine, John Hopkins University, Blatimore, Maryland, United States
The aim of genomic science is to predict biological behavior using the information stored in the DNA within each cell. Single molecule DNA sequencing using a nanopore represents the logical, end-of-the-line for development of sequencing technology in which we extract the maximum amount of information from a minimum of material. But high fidelity reads demand stringent control over both the molecular configuration in the pore and the translocation kinetics. The molecular configuration determines how the ions passing through the pore come into contact with the nucleotides, while the translocation kinetics affect the time interval in which the same nucleotides are held in the constriction as the data is acquired. We have developed a novel method that using a nanopore in a solid-state membrane to sequence double-stranded DNA (dsDNA). Using a pore with a diameter smaller than the double helix, it is possible to control both the translocation kinetics and the molecular configuration by stretching the DNA molecule in the constriction. By applying an electric force larger than the threshold for stretching, dsDNA can be impelled through the pore. Once a current blockade associated with a translocating molecule is detected, the electric field in the pore is switched in an interval much less than the translocation time to a value below the threshold for stretching, which leaves the dsDNA stretched in the pore constriction with the base-pairs tilted, while the B-form canonical structure is preserved outside the pore. In this configuration, the translocation velocity is substantially reduced from 1bp/10ns to ~1bp/2ms or stalled altogether, while the pore current is sequence dependent. We estimate that the difference current blockade A-T and C-G basepairs is about 10pA.
3:30 PM - TT8.5
Functional Abiotic Nanosystems: Agents to Probe, Manipulate, and Endow Function in Live Cells.
Siyuan Lu 1 , Anupam Madhukar 2 Show Abstract
1 Departments of Physics and Ophthalmology, University of Southern California, Los Angeles, California, United States, 2 Departments of Physics, Biomedical Engineering, Chemical Engineering and Materials Sciences, University of Southern California, Los Angeles, California, United States
Advances in the ability to synthesize and characterize nanoscale (~1-10nm) agents made of inorganic, organic, biochemical, or hybrid building blocks and designed to provide a desired function has now opened the possibility of their interfacing with live cells, in-vitro and in-vivo. We propose such a class of functional abiotic nanosystems (FANs) designed to probe, manipulate, or endow function by direct interfacing with live cells. The concept is illustrated via the example of light-activated nanoscale photodiodes capable of creating local electric fields that modulate existing voltage sensitive ion channels in excitable cells. The dynamics of the cell transmembrane potential modulation by such photovoltaic functional abiotic nanosystems (PVFANs) is modeled through an appropriate equivalent nonlinear electrical circuit. For classes of cells containing voltage sensitive ion channels the response surface of the voltage modulation as a function of the PVFAN characteristics and density is made, including those needed to exceed the typical ~10mV threshold for activating the action potentials in neuronal cells. In such a role, the FANs become therapeutic agents and act as “Cellular Prostheses”. The potential physical implementations of PVFANs will also be discussed.
3:45 PM - TT8.6
The Artificial Targeting Light Activated Nanoscissors for Gene Expression Management at Genome Level.
Tsung-Lin Tsai 2 , Yu-Sang Yang 3 , Kao-Shu Chuang 4 , Jih-Ru Hwu 4 , Dar-Bin Shieh 1 Show Abstract
2 Inst. Basic Medical Sciences, National Cheng Kung University, Tainan, 70101, Taiwan, 3 Material Science, National Tsing Hua University, Hsinchu, 300, Taiwan, 4 Chemistry, National Tsing Hua University, Hsinchu, 300, Taiwan, 1 Inst. Basic Medical Sciences and Inst. Oral Medicine, National Cheng Kung University, Tainan, 70101, Taiwan
A core shell artificial targeting light activated nanoscissors (ATLANS) consists of 13nm gold core and a self-assembled monolayer of hydrazone-modified triplex-forming-oligonucleotide was synthesized. The structure effectively protected the oligonucleotide from enzymatic and chemical degradation while attack target DNA at predesigned sequence to form double strand break under a visible light controller manner. The co-precipitation assay and Electric Field Mobility Shift Assay both revealed the specific targeting of the ATLANS to the addressed linear and plasmic DNA and spare the control plasmid with scrambled sequence. Double strand scission of the target DNA at predesigned sequence codon was achieved by illumination of the complex with an 3W LED light source in a visible light spectrum range. The double strand break induced conformation change of the plasmid DNA from form I to form III. Direct DNA sequencing revealed that the cutting site was located 12 base pairs upstream to the 3' end of the TFO as predicted by the molecular simulation modeling. The ATLANS platform provide a new development for molecular precision gene manipulation by an light controlled artificial nanodevice. The light activation mechanism enabled advanced spatial and temporal control of gene knock out at genome level that will derive a permanent effect for in vitro and in vivo biomedical applications.
TT9: Systems & Interfaces II
Tuesday PM, December 01, 2009
4:30 PM - **TT9.1
Template-Driven Synthesis of Inorganic Nanomaterials: Biomimetic Single Crystals and Dye-Sensitized Solar Cells.
Ullrich Steiner 1 2 Show Abstract
1 Department of Physics, University of Cambridge, Cambridge United Kingdom, 2 Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg Germany
Intricate structures based on organic self-assembly are the basis of all biological organisms. While the synthesis of functional inorganic materials based on organic molecular self assembly exists in nature in the form of biominerals, there are only few examples of artificial inorganic functional nanomaterials. This talk will focus on three examples that demonstrate how thin films of self-assembled block-copolymers can be employed as nano-scaffolds for the synthesis of polycrystalline and single-crystalline materials with well-defined nanostructures. One promising application of these strategies is the possible improvement of the efficiency of dye-sensitized solar cells.
5:00 PM - TT9.2
Hybrid Nanocomposite Materials through Multiscale Templating and Self-Assembly.
Jun Liu 1 , Donghai Wang 1 , Rong Kou 1 , Zhengguo Yang 1 , Daiwon Choi 1 , Zimin Nie 1 , Yuehe Lin 1 , Ilhan Aksay 2 Show Abstract
1 , Pacific Northwest National Laboratory, Richland, Washington, United States, 2 , Princeton University, Princeton, New Jersey, United States
Biological systems abound with nanocomposites with well-controlled architectures based on multiscale and multifunctional building blocks. In contrast, traditional approaches for making such materials mostly rely on mechanical or chemical mixing which usually produces a random distribution of the constitutive phases. Here we report a new, multiscale templating and self-assembly approach to produce multifunctional nanocomposite materials with well-controlled architectures. We will first discuss controlled nucleation and growth on two-dimensional templates to prepare complex nanostructured films. We will then discuss strategies to extend the two-dimesnionally templated approaches to prepare three-dimesnional hybrid nanocomposite materials through self-assembly. The potentials of the new materials for electrichemical energy storage, electrochemcial catalysis, and for biosening will be illustrated.
5:15 PM - TT9.3
Three-Domain Nanocomposites from Block Terpolymer Microphase Separation.
Morgan Stefik 1 , Francis DiSalvo 1 , Ulrich Wiesner 1 Show Abstract
1 , Cornell University, Ithaca, New York, United States
Amphiphilic diblock copolymers have been extensively applied toward the structure directing of individual/mixed materials into two-domain hybrid materials. Subsequent pyrolysis typically removes the polymer, leaving behind a material with ordered pores - also two-domains. The extension of this approach with triblock terpolymers enables the structure directing of materials with three-domains corresponding to the three chemically distinct polymer blocks. Careful selection of the polymer blocks enables the synthesis of nanocomposites with specific functionalities organized into separate domains. Control over the nanoscale ordering of multiple functional materials may lead to new materials for photonic applications as well as energy generation, storage, and conversion devices.
5:30 PM - TT9.4
Bio-templated Mimetic Chloroplast System for Photochemical Water Splitting.
Yoon Sung Nam 1 , Andrew Magyar 1 , Daeyeon Lee 2 , Jin-Woong Kim 2 , Dong Soo Yun 1 , Heechul Park 1 , Thomas Pollom 1 , David Weitz 2 , Angela Belcher 1 Show Abstract
1 , Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 , Harvard University, Cambridge, Massachusetts, United States
Over several billion years, cyanobacteria and plants have evolved highly organized photosynthetic systems to shuttle both electronic and chemical species for the efficient oxidation of water. Similar to the reaction centers in natural photosystems, molecular and metal oxide catalysts have been used to photochemically oxidize water; however, various approaches involving molecular design of ligands, surface modification, and immobilization still show low catalytic efficiencies, and recycling capability has not yet been demonstrated. Here we report a biologically templated nanostructure for visible light-driven water oxidation that employs a genetically engineered M13 virus as a scaffold to assemble a hybrid material of zinc porphyrins (photosensitizer) and iridium oxide hydrosol clusters (catalyst). Porous polymer microgels are used as an immobilization matrix to improve the structural durability of the assembled nanostructures and enable the recycling of the materials. This system evolves 94 oxygen molecules per surface iridium per minute in a prolonged manner, which corresponds to a ~ 3.5 times faster rate than the fastest value yet reported. It also maintains a substantial level of its catalytic performance after repeated uses, producing 1,278 oxygen molecules per molecule of catalysts during 4 cycles. This study suggests that biomimetic, multiscale assembly of functional components, which can improve energy transfer and structural stability, should be a promising route for significant improvement of photocatalytic water splitting.
5:45 PM - TT9.5
The Effects of Topological Constraint on the Avidity of Multivalent Polymer-antibody Conjugates.
Jason Benkoski 1 , Andrew Mason 1 , Jill La Favors 1 , Joshua Wolfe 1 Show Abstract
1 MERC, JHU Applied Physics Laboratory, Laurel, Maryland, United States
The immune system compensates for the relatively low affinity of the antibodies produced in the early stages of the immune response by synthesizing multivalent antibodies. The total binding strength, represented by the avidity constant, is equal to the product of the affinity constants for the individual hapten/receptor sites. However, under realistic conditions the individual binding sites do not act independently. Factors such as steric hindrance, intramolecular stresses, and competitive binding can significantly alter the relationship between affinity and avidity. We investigate the influence of these factors on a model system consisting of multifunctional silica nanoparticles and multi-arm polyethylene glycol (PEG). Each polymer or nanoparticle is decorated with either multiple antigens (thromboxane B2) or multiple antibodies to increase the valency. We then measure the association and dissociation in real time using Surface Plasmon Resonance Spectrometry (SPR) or Dynamic Light Scattering (DLS). The observed binding is much lower than expected on the basis of the increased valency, and even corrections for polymer chain stretching cannot account for the magnitude of the decrease.
Stefan Maier Imperial College London
Ulrich Wiesner Cornell University
Jinwoo Lee Pohang University of Science and Technology
Wednesday AM, December 02, 2009
9:30 AM - **TT10.1
Real-time Nanoscopy of the Position and Orientation of a Single Virus.
Vahid Sandoghdar 1 , Philipp Kukura 1 , Helge Ewers 2 , Alois Renn 1 , Ari Helenius 2 Show Abstract
1 Physical Chemistry, ETH Zurich, Zurich Switzerland, 2 Biochemistry, ETH Zurich, Zurich Switzerland
We present a novel colocalization methodology that combines scattering interferometry with single molecule fluorescence microscopy to visualize both position and orientation of single virions. By achieving nanometer spatial and 8 ms temporal resolution, we observed sliding and tumbling motions during rapid lateral diffusion on supported lipid bilayers and repeated back and forth rocking of single virions among nanoscopic regions separated by only a few nanometers. Our observations imply recurrent swap of receptors and binding site on the virion as well as receptor aggregation in membrane nanodomains. We shall discuss the prospects of our technique for studying virus-membrane interactions and for resolving nanoscopic dynamics of individual biological nano-objects in other environments.
10:00 AM - TT10.2
Adhesion Between Anti-EphA2 Antibody-Coated AFM Tips and Breast Cancer Cells.
Emily Paetzell 1 2 , Andrew Bogorad 1 3 , Juan Meng 1 2 , Winston Soboyejo 1 2 Show Abstract
1 Princeton Institute of Science and Technology of Materials , Princeton University, Princeton, New Jersey, United States, 2 Mechanical & Aerospace Engineering, Princeton University, Princeton, New Jersey, United States, 3 Department of Physics, Princeton University, Princeton, New Jersey, United States
This paper presents the results of atomic force microscope (AFM) measurements of the adhesion force between MDA-MB-231 breast cancer cells and anti-EphA2 antibody-coated AFM tips. As a control, the adhesive interactions are measured between Hs578Bst normal breast cells and anti-EphA2 antibody-coated AFM tips. The measurements show conclusively that the adhesive forces to breast cancer cells are almost four times greater than those to normal breast cells. The increase is attributed largely to the interactions between anti-EphA2 antibody and over-expressed EphA2 receptors that are revealed by the staining of receptor-ligand interactions. The implications of the results are discussed for the localized targeting of cancer with antibody-conjugated nanoparticles.
10:15 AM - TT10.3
Fluorescence Measurements and AFM Imaging of Bacteriorhodopsin Coupled with CdSe Quantum Dots for Optoelectronic Applications.
Nicolas Bouchonville 1 , Michael Molinari 1 , Alena Sukhanova 2 3 , Michel Troyon 1 , Igor Nabiev 2 3 Show Abstract
1 physics, LMEN EA3799, Reims University (URCA), Reims France, 2 biophysics, EA3798, URCA, Reims France, 3 biochemistry, CIC-NanoGun Consolider, Donostain San Sebastian Spain
Bacteriorhodopsin (bR) is photochromic integral membrane proteins incorporated within the natural purple membranes (PM)s of bacteria Halobacterium salinarum. Upon illumination by light, bR undergo a cyclic sequence of distinguishable photo-intermediates changing absorption in the blue-to-red region of the spectrum. The long-term stability of PM against thermal (up to 140°C), chemical, and photochemical degradation, high ionic strength and extreme pH values has made bR the most promising biological candidates for device applications. Our study investigates, on the nano-scale, the interactions of the CdSe/ZnS core/shell nanocrystals “quantum dots” (QDs) with the natural PMs containing bR. The light-absorbing bR element, retinal, is located near to the centre of the PM, 25 Å from each of the PM surfaces. Thus, when the QDs sizes are carefully chosen, the fluorescence emission from the QDs immobilized on the PM surface may be modulated due to the fluorescence resonance energy transfer (FRET) effect between the emitting QDs of selected emission colours (donors) and strongly absorbing bR (acceptor), depending on the stage of the bR photocycle. This may allow the design of a nanoscale optical switch based on a hybrid nanomaterial. Due to their interesting emission properties in the visible region of the optical spectra, we choose to use CdSe QDs made by organometallic chemistry [1,2]. The used CdSe dots have had a diameter of around 3 nm, which corresponds to their emission at 570 nm, and they were capped with a ZnS shell. As the absorption band of the bR is located at 570 nm, the emission intensity of such CdSe QDs should be modulated depending on the bR/QDs ratio if a FRET effect happened. The efficiency of the coupling between the QDs and the bR should depend on the distance between the QDs and the bR, but also on the way they are coupled (electrostatic or covalent coupling) as the PMs are negatively charged. To check this fact, the QDs surface charge was modified from negative to positive by capping them with different chemical agents: cysteine which are negatively charged, or PEG-OH slightly negative and amine positively charges. Thanks to atomic force microscopy measurements in fluid, we show that there is a perfect epitaxy of positively charged QDs on the crystalline lattice of the bR. Fluorescence measurements confirm the efficiency of the FRET effect when positively charged QDs are coupled to the bR. Starting from a solution containing only positive QDs, PM was introduced progressively in the solution to change the molar ratio between bR and QDs. For a molar ratio of 1:1, the fluorescence has almost disappeared showing the efficiency of the FRET effect and the possibility to create a hybrid optical switch. 1. Nabiev I. et al. (2008) Fluorescent colloidal particles as a detection tools in biotechnology systems. In: Colloidal Nanoparticles in Biotechnology, Wiley&Sons Inc., p 133-682. Sukhanova A. et al. (2004) Anal Biochem., 324, 60-67
10:30 AM - TT10.4
Interactions of Ibuprofen with Hybrid Lipid Bilayers Probed by Complementary Surface-Enhanced Vibrational Spectroscopies.
Janardan Kundu 1 , Carly Levin 1 , Benjamin Janesko 1 , Gustavo Scuseria 1 , Robert Raphael 2 , Naomi Halas 1 2 3 Show Abstract
1 Chemistry Dept., Rice University, Houston, Texas, United States, 2 Department of Bioengineering, Rice University, Houston, Texas, United States, 3 Department of Electrical and Computer Engineering, Rice University, Houston, Texas, United States
The incorporation of small molecules into lipid bilayers is a process of biological importance and clinical relevance that can change the material properties of cell membranes and cause deleterious side effects for certain drugs. Here we report the direct observation of the insertion of ibuprofen molecules, a well known non steroidal anti-inflammatory drug, into hybrid lipid bilayers using surface-enhanced Raman and IR spectroscopies (SERS-SEIRA). The alkanethiol-phospholipid hybrid bilayers were formed onto gold nanoshells by self-assembly, where the underlying nanoshell substrates provided the necessary enhancements for SERS and SEIRA. The spectroscopic data reveal specific interactions between ibuprofen and phospholipid moieties and indicate that the overall hydrophobicity of ibuprofen, tuned using solution pH, plays an important role in its intercalation in these membrane mimics. It is clearly observed that ibuprofen in the neutral form (at low pH) intercalates more efficiently than the anionic form (at high pH). These membrane mimics can generally be implemented for spectroscopic investigation of other biologically relevant phenomena such as role of glycolipids in membrane structure, binding of peripheral membrane proteins, and fusion of lipid vesicles with supported lipid bilayers. Our recent experimental findings on lipid exchange/transfer process, studied spectroscopically using hybrid bilayers, will also be presented.
10:45 AM - TT10.5
Pharmaceutical Nanosuspension Stabilizer Selection by Scanning Probe Microscopy.
Sudhir Verma 2 , Diane Burgess 2 , Bryan Huey 1 Show Abstract
2 Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, United States, 1 Institute of Materials Science, University of Connecticut, Storrs, Connecticut, United States
Nanosuspensions are increasingly implemented by the pharmaceutical industry, where the challenge of preventing particle agglomeration is crucial for optimal formulation performance and stability. Accordingly, an atomic force microscopy (AFM) method has been developed to investigate the interaction of common polymeric stabilizers with a model drug, ibuprofen, to determine the suitability of these surfactants for the preparation and stabilization of ibuprofen nanosuspensions. Fundamental to this study is the preparation of a model drug surface, with sub-angstrom scale roughness, allowing high resolution imaging of the adsorbed stabilizer morphology. Images clearly reveal that hydroxypropyl methyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) interact strongly with ibuprofen as evidenced by extensive surface adsorption. Particle agglomeration is hindered as a result, in agreement with dynamic light scattering particle size measurements as a function of time. AFM images obtained for PVP and Pluronic exposure, on the other hand, exhibit inadequate adsorption on the ibuprofen surface, consistent with their poor performance in stabilizing ibuprofen nanosuspensions. Such results provide a fundamental basis for future stabilizer selection and optimization. Finally, the results explain the success of top-down processing for the preparation of reliable drug nanosuspensions, usually by milling larger-particles, by allowing sufficient time (hours) for stabilizers to assemble on newly exposed surfaces.
TT11: Systems & Interfaces III
Wednesday AM, December 02, 2009
11:30 AM - **TT11.1
Programmed Molecular Assembly for Optoelectronic Materials.
Takuzo Aida 1 Show Abstract
1 Department of Chemistry and Biotechnology, The University of Tokyo, Tokyo Japan
Utilization of electronic conjugation becomes important for molecular electronics, and a variety of molecules with interesting optoelectronic properties have been reported. In 2003, we found that bucky gels, prepared by grinding carbon nanotubes in imidazolium ion-based ionic liquids [1, 2], serve as excellent capacitors and are applicable to plastic actuators by layer-by-layer casting  and stretchable electronics [4, 5]. There are many other potential applications . In 2004, we have also reported that an amphiphilic hexa-peri-hexabenzocoronene self-assembles into graphite nanotubes , which are interesting as designer electronic nanomaterials . Later, we succeeded in obtaining pseudo-crosslinked versions of this graphite nanotube by ADMET , photodimerization , redox , and metal coordination  of certain functional groups attached to the termini of the triethylene glycol side chains. These developments will allow for enhancing the practical utilities of these nanomaterials. Use of a chiral amphiphilic hexa-peri-hexabenzocoronene with stereogenic centers results in the formation of graphite nanotubes [13, 14] and coils [15, 16] with one-handed helical chirality. Water-dispersible graphite nanotubes have also been fabricated . The most recent achievement includes successful fabrication of photoconductive nanotubes with coaxial heterojunction [18, 19]. Use of click chemistry allowed dendrons to be grafted selectively on the exterior nanotube surface, leaving the interior for the second click . Using a synchrotron radiation facility, we succeeded in complete structural analysis of the graphite nanotubes . We also started a new project featuring liquid crystalline materials for electronics [22–24]. The most recent example highlights a bawl-shaped corannulene derivative, forming a hexagonal columnar LC mesophase responsive to applied electric fields.REFERENCES:  Fukushima et al., Science 2003, 300, 2072.  Fukushima et al., Small 2006, 2, 554.  Fukushima et al. ACIE 2005, 44, 2410.  Sekitani et al., Science 2008, 321, 1468.  Sekitani et al., Nature Mat. 2009, 8, 494.  Fukushima et al. CEJ (Concepts) 2007, 13, 5048.  Mullen et al., Chem. Rev. 2007, 107, 718.  Hill et al., Science 2004, 304, 1481.  Jin et al., JACS 2005, 127, 10020.  Motoyanagi et al., JACS 2006, 128, 4220.  Motoyanagi et al., JPS., Part A 2006, 44, 5120.  Wei et al., ACIE 2009, 48, in press.  Jin et al., PNAS USA 2005, 102, 10801.  Yamamoto et al., Adv. Mater. 2006, 18, 1297.  Yamamoto et al. JACS 2006, 128, 14337.  Yamamoto et al., ACIE 2008, 47, 1672.  Zhang et al., JACS 2007, 129, 719.  Yamamoto et al., Science 2006, 314, 1761.  Yamamoto et al., JACS 2007, 129, 9276.  Mynar et al., JACS 2008, 130, 1530.  Jin et al., JACS 2008, 130, 9434.  Li et al., JACS 2008, 130, 8886.  Sakurai et al., JACS 2008, 130, 13812.  Miyajima et al. JACS 2009, 131, 44.
12:00 PM - TT11.2
Encapsulation of BSA within Gelatin Nanoparticles-laden Biopolymer Film.
Jin Zhang 1 , Kevin Luzak 1 Show Abstract
1 , Univ. of Western Ontario, London, Ontario, Canada
This research aims at the development of new biodegradable polymer nanocomposites which will act as critical component to next generation medical device. Different strategies have been developed to synthesize biodegradable polymer nanocomposites. Gelatin, a natural polymer, has long been used in food and pharmaceutical industry because of its many advantageous properties, including biodegrability and unique gel-forming ability. Recently, gelatin nanoparticles have been used as non-viral vehicle to deliver DNA for gene therapy. Here, we develop an in situ route to encapsulate protein, Bovine Serum Albumin (BSA), within gelatin nanoparticles through a water-soluble crosslinking agent. The nanoencapsulation product, BSA-containing gelatin nanoparticles, has been characterized in terms of nanoparticle morphology, size and size distribution, water content, and protein release. Our research demonstrates that the average diameter of the BSA-containing gelatin nanoparticles is approximately 180nm±10nm. They can absorb 51-72% of water. The gelatin nanoencapuslated BSA afterwards were loaded in the biopolymer film with thickness around 200 µm composed of poly(2-hydroxyethyl methacrylate) (pHEMA) through the photopolymerization. The release of BSA in phosphate buffer saline (pH 7.4) from the nanoparticles and nanoparticlesloaded p(HEMA) were studied through UV-vis spectrometry. The release profile of BSA from the gelatin nanoparticulate follows a diffusion-controlled release mechanism. It is found that the releasing concentration of BSA increases with time (t), and about 80% of the encapsulated dye is released in 3 days; while, the releasing profile of BSA from the gelatin nanoparticles-loaded hydrogel has been prolonged in 10 days, over twice. These studies show that the gelatin nanoparticles are able to encapsulate water-soluble protein. The hydrgel film, pHEMA, further prolonged the releasing profile for the water soluble protein. The degradability of the polymer nanocomposites has been evaluation underway. It is expected that this new biodegradable polymer nanocomposites can be an alternative materials for consisting of implant medical device for protein therapy.
12:15 PM - TT11.3
Electrostatically Gated Solid State Nanopores with a Chemically Reactive Surface.
Zhijun Jiang 1 , Derek Stein 1 Show Abstract
1 Physics Department, Brown University, Providence, Rhode Island, United States
We are exploring the use of electrically functionalized solid-state nanopores for controlling the transport of ions and single DNA molecules in solution. We are inspired by the single-molecule regulatory capabilities of biological pores, and seek to mimic them by electrostatic means in an artificial device. Electrostatically gating surface charges in solution differs from gating in a semiconductor, and our understanding of the fluidic version is incomplete. For real surfaces in contact with ionic solution, a change in the surface potential leads to a shift in the chemical equilibrium of the ionizable surface groups that contribute significantly to the surface charge density. Here we present a theoretical model of electrostatic gating that reveals the influence of pH, salt concentration, and specific chemical surface groups. We have also made electrostatically gated nanopore devices in which an applied gate potential can influence the density of mobile counter-ions inside the pore. The conductance of a nanopore is dominated by the density of mobile counter-ions attracted by the surface charges at low salt concentrations, where the Debye length, which characterizing electrostatic screening, is a few nm. Our experiments show how the surface charge density is controlled by both capacitive charging and the surface chemistry. Finally, these devices allow us to probe the electrostatic interaction between the nanopore surface and negatively charged DNA molecules in the regime of double-layer overlap. A negatively charged inner nanopore surface should repel DNA, and hinder its entry into the nanopore. Positive surface charges, on the other hand, will attract DNA, and translocation should be favored. The study of electrostatically gated nanopores will help us better understand Coulomb interactions with charged molecules, and reveal the possibilities for using “electro-fluidic” technology to study single molecules.
12:30 PM - TT11.4
Structure-dependent enhancement of Fluorescent Emission from Nanopatterned Silk Films.
Jessica Mondia 1 , Jason Amsden 1 , Svetlana Boriskina 2 , Rui Li 2 , David Kaplan 1 , Luca Dal Negro 2 , Fiorenzo Omenetto 1 3 Show Abstract
1 Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, United States, 2 Department of Electrical and Computer Engineering, Boston University, Boston, Massachusetts, United States, 3 Department of Physics, Tufts University, Medford, Massachusetts, United States
We present results on nanostructure-dependent fluorescence enhancement and spectral selectivity by nanopatterning doped silk films. Specifically, the nanopatterned silk is doped with a biomedically relevant fluorescent emitter, Rose Bengal. The films are made by adding Rose Bengal powder (<0.1% wt.) to a water-based solution of fibroin extracted from silkworm (Bombyx mori) silk cocoons. The resulting doped solution is spun coat onto glass substrates and allowed to dry. The resulting film (~500nm thick) is then brought into contact with an e-beam written Si nanopatterned template and the patterns are transferred into the silk by contact imprinting. The resulting silk film patterns comprise of square lattice arrays of holes with diameters of 200nm, depth of 30nm and varying center-to center separation (i.e. lattice pitch) ranging from 250-700nm. Spectrally resolved measurements were performed by employing a hyperspectral CCD (CRI Nuance FX) camera attached to an Olympus IX 71 microscope. A mercury lamp coupled with an excitation filter and dichroic mirror were used to stimulate the fluorescence within the doped silk film. The spectral data is acquired in an epi-illumination geometry by employing a 4X NA 0.13 microscope Olympus UPanFLN objective to deliver the excitation and collect the emitted spectra. Since Rose Bengal has a broad emission bandwidth (560-700nm), enhancement of specific wavelength regions are observed in the hyperspectral images as a function of the different lattice pitch of the patterned nanostructures. The results can be qualitatively understood using classical diffraction grating calculations. The enhancement is a function of matching either the excitation, emission or both to the supported diffracted orders of the periodic structure. The brightest fluorescence is found to correspond to the nanopatterned structures with 400nm pitch which yield twice the amount of fluorescence than an unpatterned portion of the film. Further, the peak wavelength for the 400 nm pitch structure appears to experience a spectral shift that matches a diffraction order of the patterned surface. These results can be of interest for the rapid identification of fluorescent signatures on biological structures by appropriately designed surface patterns and to enhance and spectrally filter light emission in bio-optical devices.
TT12: Plasmonics in Bionanoscience
Wednesday PM, December 02, 2009
2:30 PM - TT12.1
Approaches to Biochemical Sensing with Plasmonic Nanophotonics.
Stefan Maier 1 Show Abstract
1 Physics Department, Imperial College, London United Kingdom
This talk will survey prominent biochemical sensing technologies based on light confinement utilizing plasmonic and metamaterials concepts. Topics will include surface enhanced Raman scattering, surface enhanced infrared absorption spectroscopy, and localized surface plasmon resonance sensors, amongst others.
2:45 PM - **TT12.2
Nanoplasmonics with Biomolecules.
Jochen Feldmann 1 Show Abstract
1 , LMU Muenchen, Muenchen Germany
I will report on our efforts to use the unique optical properties of gold nanoparticles for the analysis and the control of biomolecular processes. We have investigated protein linked gold nanoparticle dimers and gold nanostars for enhancing and shaping fluorescence and Raman spectra Controlled optical heating of gold nanoparticles can be used to detect a single base-pair mismatch within a DNA or to induce local melting on a gel-like phospholipid membrane.
3:15 PM - TT12.3
Release of Multiple Species from Gold Nanorods by Ultrafast Laser Excitation.
Kimberly Hamad-Schifferli 1 Show Abstract
1 Biological Engineering and Mechanical Engineering, MIT, Cambridge, Massachusetts, United States
We demonstrate the use of gold nanorods (NRs) to control the release of multiple species independently. Ultrafast laser irradiation in resonance with their longitudinal surface plasmon resonance (LSP) can heat NRs to a high local temperature, inducing melting. This triggered melting has been exploited for controlled release of biomolecules conjugated to the NRs. Because the LSP is tunable by changing NR aspect ratio (AR), NRs with different ARs can be excited independently at different wavelengths. We exploit this property for selective and mutually exclusive release of two distinct DNA oligonucleotides, and show that the released DNA is still functional. Control over the surface chemistry of the NRs is key as the ligand can affect the thermal dissipation of the NRs. If surface chemistry is not controlled it can prevent NR biofunctionalization and limit stability in physiological buffers. Release is efficient, where 50-80% of loaded DNA is released selectively. Laser fluence governs the degree of NR melting, therefore specificity and degree of release are externally tunable. Since conjugation requires only a simple thiol, it is potentially applicable to a range of molecules. This method is expandable, as tuning NR synthesis parameters could extend this approach beyond two species. NR surface chemistry is customizable, so they can accommodate different physiological environments. Others have also demonstrated active targeting by decorating the NRs with moieties such as antibodies and cell receptor ligands. These characteristics show that triggered release from NRs is a potentially powerful technique for improving drug delivery strategies.
3:30 PM - TT12.4
Single Domain Spectroscopy of Biological Photonic Crystals using Plasmonic Beacons.
Nicholas Borys 1 , Debansu Chaudhuri 1 , Jeremy Galusha 2 , Michael Bartl 2 , John Lupton 1 Show Abstract
1 Physics, University of Utah, Salt Lake City, Utah, United States, 2 Chemistry, University of Utah, Salt Lake City, Utah, United States
Nature offers a wide variety of complex nanostructures which have yet to be fabricated in the laboratory. Examples include photonic crystals formed in the exoskeleton of certain weevils. It was recently demonstrated that a particular class of animals offers a unique diamond crystal structure, which as yet cannot be fabricated using top-down approaches . Biological photonic structures tend to be structurally disordered and thus require high resolution optical techniques for precise characterization. Conventional transmission microscopy is limited by strong light scattering, preventing the identification of single domains of the chitin crystal. The application of near field techniques also poses problems due to the strong disorder and surface roughness present on beetle scales. We have explored a novel type of transmission microscopy, using surface plasmon-enhanced non-linear light emission from silver metal nanoparticles conventionally employed in surface-enhanced Raman scattering [2-3]. The non-linear light emission is spectrally broad but occurs from sub-diffraction cross sections. The silver nanobeacons readily couple to the photonic crystal, allowing the identification of different crystal domains. These different domains vary due to the particular crystal facet being probed as well as the periodicity of the dielectric. Using this technique, we can identify domain boundaries on length scales of less than 800 nm . Bio-inspired optical materials are often viewed critically due to the strong scattering present and the inherent disorder. Metallic light sources provide a route to overcoming these disorder limitations and suggest a pathway to designing more complex photonic circuitry based on nature’s toolbox.  Galusha et al. Phys. Rev. E 77, 050904 (2008). Walter et al. Phys. Rev. Lett. 98, 137401 (2007).  Walter et al. J. Am. Chem. Soc. 130, 16830 (2008). Chaudhuri et al. Nano Lett. 9, 952 (2009).