Peter Kiesel Palo Alto Research Center
David Nolte Purdue University
Xudong (Sherman) Fan University of Missouri
George Hong Millipore Corporation
AA1: Biomedical Devices for Resources Limited Setting
Monday PM, December 01, 2008
Gardner A/B (Sheraton)
2:30 PM - **AA1.1
Design Criteria for Development of Next Generation Diagnostics for Resource-limited Settings.
J. Paul Robinson 1 Show Abstract
1 Bindley Bioscience Center, Purdue University, W.Lafayette, Indiana, United States
The desire to facilitate development of diagnostic tools for resource limited settings is laudable. There are fundamental constraints that must be adhered to in order to provide realistic and useful solutions. The trend to take advantage of publicity generated by reference to resource-poor settings is an unfortunate one. Thus the first criteria for consideration is a genuine desire to produce technologies that can operate in remote regions with little to no infrastructure. Financial considerations based on Western systems design criteria rarely function in these environments. Enormous resources are squandered into what amounts to basic research when what is needed is applied realistic solutions. The impact of these failures is often felt on programs that fully embrace the needs of resource limited environments but do not carry the publicity and unrealistic expectations of “next-gen” promises. There are two well defined directions to create successful programs, but they have different timelines and expectations. Firstly, by engaging innovative manufacturing techniques and state-of-art technologies, small, low cost, effective diagnostic solutions can be developed. With miniaturization and cost reduction of electronic components comes a legitimate opportunity to produce robust tools. When microfluidic devices become manufacturable at low costs, in small quantities, these too bring enhanced utility for resource limited regions. Many of these technologies are not, however capable of providing immediate solutions. Many are 5 or more years away from being useful in the field at affordable costs. Therefore, a secondary solution should be seriously considered. This is an approach driven by minimalist engineering using current technologies and tools, re-engineered for specific and limited tasks.This is a practical solution that can often use mature chemistry and mature engineering and manufacturing approaches but bring low cost tools rapidly to the market. The advantage of this approach is that its impact can be rapid, effective and immediate. The reason it is rarely followed is that there is no driving force by Western needs and thus its economics are heavily dependent upon humanitarian driven objectives rather than high profit business goals. Regarding specific design criteria, there are 7 critical aspects: Test accuracy, Power utilization, physical size, direct result readout, ease of use (low training), robustness, and test cost. In addition to these critical aspects there are many more that it is desirable to consider. Depending on the nature of the test or device issues such as manufacturing complexity, speed of test result, environmental impact (heat, humidity), maintenance, and reliability are all important. Complex devices that can produce multiple types of tests are rarely useful in recourse limited regions where very specific needs frequently demand a compromise that might not be acceptable in other environments.
3:00 PM - **AA1.2
Developing Point-of-Care Diagnostics for Resource-Limited Settings.
William Rodriguez 1 2 Show Abstract
1 , Massachusetts General Hospital, Charlestown, Massachusetts, United States, 2 , Harvard Medical School, Boston, Massachusetts, United States
3:30 PM - AA1.3
Spatially Modulated Emission for Point-of-Care Flow Cytometer.
Noble Johnson 1 , Peter Kiesel 1 , Michael Bassler 1 , Markus Beck 1 Show Abstract
1 , Palo Alto Research Center, Palo Alto, California, United States
Virtually all commercial flow cytometers rely on optical interaction with the bio-particles for characterization, through fluorescence, scattering, or absorption processes. And all use the same basic optical configuration, namely, intense illumination of the bio-particle as it speeds through a highly localized spot, which generally involves a complex arrangement of optics (e.g., lenses, mirrors, apertures, and filters). This highly focused beam of light is required to achieve usable sensitivity since the signal is proportional to the photon flux density. While such instruments are extensively used in research and clinical laboratories, they do not meet the challenging practical requirements for point-of-care (POC) diagnostics in resource-limited settings, such as CD4 monitoring which is required for proper treatment of HIV infected persons.In this presentation we will describe and illustrate a fundamentally new design of the optical detection system that delivers high effective sensitivity (i.e., high signal-to-noise discrimination) without complex optics or bulky, expensive light sources to enable a flow cytometer that combines high performance, robustness, compactness, low cost, and ease of use. The enabling innovation is termed “spatially modulated emission/excitation” and involves relative movement between a fluorescing bio-particle and a patterned environment. This produces a time-modulated signal that is analyzed with real-time correlation techniques. The advantage is high discrimination of the particle signal from background noise. In addition the technique can distinguish signals from closely spaced particles. The cost benefit arises from the ability to replace expensive, bulky components with inexpensive ones that can be readily integrated on a fluidic chip and by eliminating the need for sophisticated optics and critical optical alignment. Potential examples include light emitting diodes for excitation and PIN diodes for photo-detection.The technology will be demonstrated with characterization of individual fluorescent beads (diameters: 6 microns, 2 microns and 0.6 micron), detection of tagged CD4 cells, and CD4 counting in whole blood.
3:45 PM - AA1.4
Biodetection Elements: Innovative Tools for Medical Diagnostics.
Aaron Anderson 1 , Andrew Beveridge 3 , Andrew Dattelbaum 2 , Karen Grace 4 , Wynne Grace 1 , Jennifer Martinez 2 , Harshini Mukundan 1 , Jurgen Schmidt 3 , Hongzhi Xie 1 , Basil Swanson 1 Show Abstract
1 Physical Chemistry & Applied Spectroscopy, Los Alamos National Laboratory, Los Alamos, New Mexico, United States, 3 Advanced Measurement Science, Los Alamos National Laboratory, Los Alamos, New Mexico, United States, 2 Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Los Alamos, New Mexico, United States, 4 Space Instrumentation Systems, Los Alamos National Laboratory, Los Alamos, New Mexico, United States
Much biodetection research, including our own, involves anti- or counter-terror applications, namely the detection of potential biological threat agents such as B. anthracis (anthrax), V. cholerae (cholera), and C. botulinum (botulism). While important, focusing solely on biothreat agents ignores the public health risk that undetected diseases present, especially in undeveloped or developing nations where good medical services are rare and cost prohibitive for much of the population. Realizing this problem, our team is also developing detection methods against a variety of disease targets such as tuberculosis and influenza. To detect these targets, we employ a variety of tools including our waveguide-based optical sensor, robust and flexible thin-films at the bio-inorganic interface, photo-stable reporters that enable multiplex detection, and novel and resilient recognition elements such as peptides and carbohydrates. Finally, we are combining these tools with an innovative signal modulation approach to nucleic acid detection that requires no additional reagents. Taken together, these elements represent a significant step toward a biosensor system that is robust, sensitive, flexible, specific, and autonomous.
4:00 PM - AA1.5
Enhancement of Optical Detection in Composite Hydrogel – Porous Silicon Biosensors.
Lisa Bonanno 1 , Lisa DeLouise 2 1 Show Abstract
1 Biomedical Engineering, University of Rochester, Rochester, New York, United States, 2 Dermatology, University of Rochester, Rochester, New York, United States
The current methods of laboratory-based clinical testing suffer from large operational costs and long turn-around time for results. Innovation of new diagnostic methods is pertinent to improve long-term patient health care. Porous silicon (PSi) possesses many ideal characteristics as a diagnostic biosensor substrate including its inexpensive fabrication, intrinsic optical and filtering properties, and compatibility with array and microfluidic technologies. These properties of PSi offer advantages over current methodologies by its potential for cheap, uncomplicated high-throughput analysis at point-of-care. PSi biosensor development for immunoassays has been widely established in research literature; however, current sensitivity limitations pose restrictions to their potential use in diagnosis of disease and drug screening applications. The focus of this research will utilize innovative material design in sensor format and competitive immunoassay techniques to improve detection sensitivity of the biosensor device while maintaining the advantages of not using any secondary label molecule. Properties of target-responsive hydrogels are taken advantage of to enhance the sensor response (effective optical thickness change) after target capture. Preliminary data supports the feasibility of a composite design which encapsulates the PSi sensor with a polyacrylamide hydrogel. We have been successful in monitoring both dielectric and morphological changes in the composite sensor device. Initial studies have targeted the detection of opiate drugs in urine specimens as a proof of concept small molecule diagnostic test. However, more broadly the rational design criteria for developing PSi optical biosensors and label free signal enhancement methodologies developed here could be extended to detect multiple targets in clinical applications. One could envision future development of this technology into a dermal sweat patch drug screening method with intrinsic optical sensing capability.
AA2: Waveguide Based Sensors
Monday PM, December 01, 2008
Gardner A/B (Sheraton)
4:30 PM - **AA2.1
Optical Fiber Microarrays for Chemical and Biological Measurements.
David Walt 1 , Christopher LaFratta 1 , Michael Webb 1 , Zhaohui Li 1 , Hans-Heiner Gorris 1 , Ryan Hayman 1 Show Abstract
1 Chemistry Department, Tufts University, Medford, Massachusetts, United States
We have used coherent imaging fiber arrays as a platform for preparing chemical sensors and biosensors. Sensors can be made with spatially-discrete sensing sites for multi-analyte determinations. Micrometer sized sensors have been fabricated by etching the cores of an optical imaging fiber to create microwells and loading them with microspheres. These arrays possess both high sensitivity and reproducibility and can be used for making thousands of measurements simultaneously such as for genetic analysis or for the analysis of complex biological fluids. Both optical and optoelectrochemical arrays have been used for multiplexed sensing. In another scheme, the arrays can be used for single molecule detection. In this format, individual molecules, such as enzymes, can be trapped in the microwells by sealing each microwell with a silicone gasket. The enzyme molecules catalyze the formation of a fluorescent product that can be detected readily. The kinetic properties of hundreds to thousands of single enzyme molecules can be monitored simultaneously using this format. By observing the stochastic nature of the single molecule responses, new mechanistic insights into the fundamental nature of the enzymes can be obtained.
5:00 PM - **AA2.2
Silicon-based Planar Optofluidics for Single Particle Analysis.
Holger Schmidt 1 , Sergei Kuehn 1 , Philip Measor 1 , Mikhail Rudenko 1 , Evan Lunt 2 , Brian Phillips 2 , Aaron Hawkins 2 Show Abstract
1 School of Engineering, UC Santa Cruz, Santa Cruz, California, United States, 2 ECEn Department, Brigham Young University, Provo, Utah, United States
Integrated optical waveguides are becoming an essential part of microfluidic devices for biomedical sensing. One promising avenue to such planar optofluidics is the use of antiresonant reflecting optical (ARROW) waveguides. Liquid-core ARROWs allow for optimum light-sample interaction, and combining them with solid-core ARROWs allows for devising two-dimensional waveguide structures in which fluidic and optical access points can be placed independently. We review silicon-based optofluidic ARROW devices for use in biomedical sensing. Waveguide fabrication based on a sacrificial layer technique and issues related to this method will be discussed. Optical waveguide properties for mode areas on the order of ten microns squared will also be reviewed. These interconnected ARROWs have been used for highly sensitive optical detection and analysis of a variety of particles. We will describe the implementation of advanced optical spectroscopy methods such as fluorescence correlation spectroscopy on these optofluidic chips and their use to detect single dye molecules, liposomes, and bacteriophages. The prospects for additional all-optical particle control via optically induced motion and trapping, as well as the addition of nanoscale functionalities via nanopores will be discussed. Different aspects of this work were funded by the National Institutes of Health (grants R21EB003430 and R01EB006097), the National Science Foundation (grant ECS-0528730), the W.M. Keck Foundation (National Academies Keck Futures Initiative Award NAKFI-Nano14), and the California Systemwide Biotechnology Research & Education Program Training Program (grant UC-GREAT 2005-245).
5:30 PM - AA2.3
Miniature Bio-Chemical Surface Plasmon Resonance Sensor on Standard Optical Fibers.
Yanina Shevchenko 1 , David Blair 2 , Nur Ahamad 2 , Anatoli Ianoul 2 , Maria DeRosa 2 , Jacques Albert 1 Show Abstract
1 Electronics, Carleton University, Ottawa, Ontario, Canada, 2 Chemistry, Carleton University, Ottawa, Ontario, Canada
Surface Plasmon Resonance (SPR) enables optical biosensors to be simple and to operate in the label-free regime. In particular, optical fiber-based SPR sensors are interesting due to their compactness; however one of the main drawbacks of the existing SPR fiber sensors is their limited operating range in terms of wavelengths and sensing medium refractive indices. The SPR fiber biosensor presented here can be used in media with a wide range of refractive indices and allows for precise control over the SPR excitation conditions . The sensor consists of an unmodified standard telecommunications single-mode fiber (Corning SMF 28) coated with a nanometer scale thin film of gold. The plasmon wave is excited on the surface of the gold film by fiber cladding modes generated with a tilted grating imprinted in the fiber’s core. The grating couples the light from the core mode to a set of cladding modes in a wavelength selective fashion; each of those cladding modes strikes the cladding-gold interface at a different incidence angle and can be used to excite a SPR. The tilt angle of the grating is used to determine the operating range of the sensor: our experimental results will indicate how the sensor can be used to work in aqueous solutions (with a tilt of 10°) as well as in high refractive index oils (with a tilt of 6°). The metal film supporting the SPR has a strong impact on the SPR properties. Two different theoretical models describing SPR in planar structures indicate that the film’s thickness influences both the SPR wavelength and the strength of the coupling of the cladding modes to the plasmon mode. The roughness of the film affects the width of SPR which in turn determines the precision of the sensor. Theoretical results indicate that the optimal thickness varies from 20 to 60 nm depending on wavelength. This finding will be supported by experimental results obtained at different wavelengths for the cylindrical geometry of our sensors. The proposed sensor configuration can be used in transmission and reflection. Reflection allows the sensor head to be very compact, making it possible to conduct experiments in small volumes with a controlled environment and even remotely (via the optical fiber used to make the sensor). The sensor has been tested to detect the attachment of short DNA sequences consisting of 15 bases , and most recently to detect the presence of alpha-thrombin proteins in solution. Experimental results will be confirmed with AFM imaging to reveal the density of the proteins attached to the gold surface. We will also present results and discuss the effect of the guided light polarization on the sensors performance. References Y. Y. Shevchenko and J. Albert, Opt. Lett. 32, 3, 211(2007). Y. Y. Shevchenko, D. A. D. Blair, M. C. Derosa, and J. Albert., Proc. CLEO/QELS 2008 (CMJ4).
Peter Kiesel Palo Alto Research Center
David Nolte Purdue University
Xudong (Sherman) Fan University of Missouri
George Hong Millipore Corporation
AA3: Interferometric Biosensors
Tuesday AM, December 02, 2008
Gardner A/B (Sheraton)
9:30 AM - AA3.1
Rapid Chemical Vapor Sensing and Micro Gas Chromatography Detection Using Optofluidic Ring Resonators.
Yuze Sun 1 , Siyka Shopova 1 , Ian White 1 , Hongying Zhu 1 , Greg Frye-Mason 2 , Shiou-jyh Ja 3 , Aaron Thompson 3 , Xudong Fan 1 Show Abstract
1 Biological Engineering, University of Missouri, Columbia, Missouri, United States, 2 , ICx Nomadics, Albuquerque, New Mexico, United States, 3 , ICx Nomadics, Stillwater, Oklahoma, United States
We develop rapid chemical vapor sensors based on optofluidic ring resonators (OFRRs). An OFRR is a micro-sized thin-walled glass capillary; the circular cross-section of the capillary acts as an optical ring resonator while the whispering gallery modes or circulating waveguide modes (WGMs) supported by the ring resonator interact with the vapor samples passing through the core. The OFRR interior surface is coated with a vapor-sensitive polymer. The analyte and polymer interaction causes the polymer refractive index (RI) and the thickness to change, which is detected as a WGM spectral shift. Owing to the excellent fluidics, the OFRR exhibits sub-second detection and recovery time with a flow rate of 1 mL/min, a few orders of magnitude lower than that in the existing optical vapor sensors. Ethanol and hexane vapors are used as a model system and two kinds of polymer coatings, Carbowax-400 and OV-17, are used to demonstrate discriminative responses to different vapors. We further demonstrate that the OFRR can be employed as a micro gas chromatography (μGC) with on-column separation and detection of mixtures of different analytes. Carbowax-400 is coated on the interior surface of OFRR as the stationary phase. Ethanol, toluene, decane and DMMP, representative of various polarity and volatility analytes, are used as a model system. All of them have unique retention times when interacting with the Carbowax-400. Compared to the conventional GC system, the OFRR μGC has the advantage of small size, rapid response, and high selectivity over a short length of column. To better understand the OFRR vapor sensing capability, we carry out simulation using a four-layer Mie model. Both OFRR RI sensitivity and thickness sensitivity are studied as a function of polymer thickness and wall thickness. We have found that when the polymer thickness is 1 μm, assuming that vapor molecule doping effect induced RI change is dominant, a detection limit of 2.5x10-7 RIU can be achieved, corresponding to a vapor concentration on the order of 0.1 ppm at room temperature and 1 atm. Also, when the polymer shrinking/swelling effect is dominant, the detection limit for a typical chemical vapor is 3.3 ppm. Theoretical analysis further shows that the OFRR sensitivity generally increases with increased polymer layer thickness. However, a thicker polymer layer can degrade OFRR sensing response time due to the diffusion of vapor molecules into the polymer. Therefore, in practice, it is important to optimize the polymer thickness according to the analyte and polymer properties. The OFRR based vapor sensor can be utilized in many applications such as environmental protection, homeland security, and battlefield sensing for quick chemical vapor analysis. It may also find application for breath analysis in hospitals for disease diagnosis.
9:45 AM - AA3.2
Optical Interferometric Biosensor with PMMA as Functional Layer.
Wenhui Wang 1 , Xiaodong Ma 1 , Lisa-Jo Clarizia 2 , Xingwei Wang 1 , Melisenda J. McDonald 2 Show Abstract
1 Dept. of Electrical and Computer Engineering, UMass Lowell, Lowell, Massachusetts, United States, 2 Dept. of Chemistry, UMass Lowell, Lowell, Massachusetts, United States
An optical interferometer is well known for its simple structure and high sensitivity to “change of optical path difference” (OPD). Thin film interferometric biosensor has the capability of label-free sensing based on the OPD change caused by binding of biomaterial on the surface. Usually, dielectric materials such as silica were used and surface treatment (generally silanization) was necessary to ensure immobilization of the probe biomaterial on the sensor surface. Recently, Clarizia and McDonald have shown that a PMMA substrate used in an immunoassay system can not only immobilize Human IgG antibodies but can place them in the proper orientation. Correct orientation means that more protein immobilized on the fiber will have the capability to bind their specific targets. A multi-layer interferometric biosensor with thin PMMA as functional layer to bind biomaterial was designed, fabricated and tested. The fabrication process is simple without chemical surface treatment. Sensors with 1.5um silicon dioxide and 0.1um PMMA layer were tested based on a wide-band spectrum measurement system. Anti-human IgG and anti-murine IgG were used to verify the capability of specific and nonspecific detection, respectively. Experimental results have revealed a nearly six-fold greater thickness change with specific than with non-specific binding. Further, thermal dependent drift and long time stability tests have demonstrated that the sensor was resistant to environmental fluctuation. By employment of thinner oxide (<0.5um) and polymer (< 0.05um) layers, the sensitivity of the sensor should be further enhanced whilst the thermal dependent drift will be decreased further.
10:00 AM - AA3.3
Reactive WGM Bio-sensing of a Single Influenza A Virion: An Unlabeled Means for Estimating Virion Size and Mass.
Frank Vollmer 1 , Stephen Arnold 2 , David Keng 2 Show Abstract
1 , Rowland Institute at Harvard, Cambridge , Massachusetts, United States, 2 Microparticle Photophysics Lab, Polytechnic University, Brooklyn, New York, United States
10:15 AM - AA3.4
Detection Limits of Captured Protein on the BioCD.
David Nolte 1 , Ming Zhao 1 , Xuefeng Wang 1 Show Abstract
1 Physics, Purdue University, West Lafayette, Indiana, United States
The BioCD is an interferometric biosensor that detects protein captured by antibody arrays. It has two key attributes that separates this technology from other optical or interferometric biosensor technologies. The first is the intrinsic scalability of surface-normal interferometric detection with capacity for hundreds or thousands of assays per disc because the footprint per measurement can be as small as a square micron. The second is the high-speed laser scanning that moves the detection frequency far off 1/f noise allowing repeatable surface height sensitivity to below 50 picometers. These two simple attributes provide the potential for high-speed label-free multi-analyte assays with future applications in diagnostics, prognostics and drug discovery.The sensor readout is performed on a spinning disc using a common-path interferometric configuration that is stable and sensitive to sub-monolayer coverage of captured protein . Protein is detected using phase quadrature that converts phase to intensity modulation using local generation of signal and reference to lock the relative phase of the waves. Several different classes of the BioCD have been developed, differentiated by the means of generating the phase-locked reference. These include the microdiffraction (MD) class, the phase contrast (PC) class , the adaptive optical (AO) class and the in-line (IL) class  of BioCD. Of these different quadrature classes, the in-line BioCD has the highest sensitivity with a detection sensitivity of 0.25 pg/mm. The minimum detectable mass is set by simple scaling relations. The metrology limit is set by surface roughness combined with repositioning offset between pre- and post-incubation scans. Optimal sensitivity is achieved by critical sampling of protein spots in radial arrays. We imaged a single 100 micron wide protein spot with focal spot sizes of 1, 5 and 10 microns and observe a square-root scaling as a function of the number of pixels per protein spot.The current generation of the BioCD is based on silicon. We discuss recent progress in the silicon BioCD that consists of patterned protein on thermal oxide on silicon. The thermal oxide provides the condition for in-line interferometric quadrature for stable common-path interferometry of bound protein on the disc surface.M. Zhao, W. Cho, F. Regnier, and D. Nolte, "Differential phase-contrast BioCD biosensor," Appl. Opt., vol. 46, pp. 6196-6209, 2007.X. Wang, M. Zhao, and D. D. Nolte, "Common-Path Interferometric Detection of Protein on the BioCD," Appl. Opt., vol. 46, pp. 7836-7849, 2007.
10:30 AM - AA3.5
Label-free Optical Detection of Molecular Interactions by Molecular Interferometric Imaging.
Ming Zhao 1 , Xuefeng Wang 1 , Davie Nolte 1 Show Abstract
1 Physics, Purdue University, West Lafayette, Indiana, United States
Direct optical detection of biomolecules relies on virtual optical dipole transitions that are the origin of refractive index in bulk materials. In the single-molecule limit, the molecule causes dipole scattering with an associated phase lag. We have developed molecular interferometric imaging (MI2) biosensor that combines ultra-stable interferometry with shot-noise limited characteristics of a CCD camera to measure this phase lag, and have achieved shot-noise or surface roughness limited detection of immobilized biomolecules, with close to single molecule sensitivity in the metrology limit. We have applied this technique to study kinetic interactions between biomolecules.MI2 is based on common-path in-line quadrature interferometry combined with far-field optical imaging. The substrate is a simple thermal oxide on silicon with a thickness at or near the condition of phase-quadrature that imprints a relative phase of pi/2 on the partial reflections from the oxide layer. The presence of biomolecules on the oxide produces local phase shifts that are converted to far-field intensity shifts and imaged directly by a CCD camera. The interferometry is stable because of the common-path geometry, is simple because of the non-resonant conditions that allow surface-normal incidence with no polarization control, and is sensitive to only tens of picometers average surface height displacement. We have achieved surface roughness limited sensitivity of protein profile at 15 pm within a 0.4 micron diffraction limited pixel. For a protein density of 1.3 g/cm3, this corresponds to a minimum detectable mass of 3 attograms at the metrology limit, which is 12 antibody molecules of size 150 kDa, close to the single-molecule limit.We have applied MI2 to immunoassays applications. With a sandwich immunoassay, we have achieved a concentration detection limit of 50 pg/mL for detection of the cytokine interleukin-5. We have also applied MI2 in the study of real-time kinetics of molecular interactions. We compared the MI2 system under 7x magnification with a commercial SPR system (Reichert S7000) by measuring association of anti-rabbit against immobilized rabbit in real-time. The scaling mass sensitivity of the MI2 system under 7x magnification in real-time binding experiments is 2 pg/mm, comparable to or better than commercial SPR systems. The association of rabbit IgG onto immobilized protein A/G was measured at different concentrations, with an association rate of 2.8e4 M-1sec-1.The extreme simplicity of the substrate and optical read-out, the high molecular surface sensitivity, combined with scalability to high multiplexing, make MI2 a promising analytical assay tool for high-throughput screening and diagnostics, and for the study of protein interaction kinetics.This work was supported by sponsored research from QuadraSpec, Inc. through the Purdue Research Foundation.
10:45 AM - AA3.6
Microfluidic Integrated Glass Optical Resonators for Label-free Biological Detection.
Juejun Hu 1 , Nathan Carlie 2 , Xiaochen Sun 1 , Laeticia Petit 2 , Bogdan Zdyrko 2 , Anu Agarwal 1 , Kathleen Richardson 2 , Igor Luzinov 2 , Lionel Kimerling 1 Show Abstract
1 Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States, 2 School of Materials Science & Engineering, COMSET, Clemson University, Clemson, South Carolina, United States
The use of novel high-index chalcogenide glass materials for optical resonator sensors presents several competitive advantages, including compact photonic integration, robust coupling to planar waveguides, low temperature sensitivity, and low-loss device operation in near-infrared water optical transparency window for sensing molecules in an aqueous environment.We report the design, processing and characterization of high-index-contrast, planar waveguide-coupled chalcogenide glass optical resonators for sensing applications with a cavity Q-factor exceeding 2E5, the highest Q value reported in chalcogenide resonators. We have developed a set of processing techniques and protocols that allow us to fabricate integrated devices in chalcogenide glass materials leveraging on existing standard silicon-CMOS foundry facilities. By incorporating a new pulley-type coupler design, which effectively relieves the fabrication challenge often associated with high-index-contrast resonators, our devices are processed using widely-available CMOS-line UV stepper lithography suitable for low-cost mass production. A low-temperature post-fabrication rapid thermal reflow process is shown to reduce the optical loss induced by sidewall roughness scattering and improve resonator Q-factor. Prototypical sensor device is fabricated by integrating high-Q glass resonators with polymer microfluidic channels for analyte transport, and we measure RI sensitivity as high as 182 nm/RIU, more than twice the value measured in Si resonators, and a refractive index resolution of 1E-6 RIU in aqueous solutions. Numerical simulations employing a Lorentzian peak-fitting algorithm are performed to investigate the RI detection limit of resonator-based refractometry sensors. Based on the simulation results, a new figure of merit, noise-normalized detection limit is introduced to quantitatively evaluate the performance matrices of different refractometry sensor techniques and a cross-technology-platform comparison is presented. We demonstrate that glass optical resonator sensors feature a promising technology for label-free biological detection.
AA4: Defraction Biosensors
Tuesday PM, December 02, 2008
Gardner A/B (Sheraton)
11:30 AM - **AA4.1
Photonic Crystals: A Platform for Label-free and Enhanced Fluorescence Biomolecular and Cellular Assays.
Brian Cunningham 1 Show Abstract
1 Electrical and Computer Engineering, University of Illinois, Urbana, Illinois, United States
Photonic crystal surfaces represent a class of resonant optical structures that are capable of supporting high intensity electromagnetic standing waves with near-field and far-field properties that can be exploited for high sensitivity detection of biomolecules and cells. While modulation of the resonant wavelength of a photonic crystal by the dielectric permittivity of adsorbed biomaterials enables label-free detection, the resonance can also be tuned to coincide with the excitation wavelength of common fluorescent tags - including organic molecules and semiconductor quantum dots. Photonic crystals are also capable of efficiently channeling fluorescent emission into a preferred direction for enhanced extraction efficiency. Photonic crystals can be designed to support multiple resonant modes that can perform label free detection, enhanced fluorescence excitation, and enhanced fluorescence extraction simultaneously on the same device. Because photonic crystal surfaces may be inexpensively produced over large surface areas by nanoreplica molding processes, they can be incorporated into disposable labware for applications such as pharmaceutical high throughput screening. In this talk, the optical properties of surface photonic crystals will be reviewed and several applications will be described, including results from screening a 200,000-member chemical compound library for inhibitors of protein-DNA interactions, gene expression microarrays, and high sensitivity of protein biomarkers.
12:00 PM - AA4.2
Fabrication of Photonic Crystal-based Nanosensors for Tumor Marker Detection.
Ruey-an Doong 1 , Sue-min Chang 2 , Han-Yun Cheng 1 Show Abstract
1 Dept. of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu Taiwan, 2 Institute of Environmental Engineering, National Chiao Tung University, Hsinchu Taiwan
The fabrication of Porous materials such as photonic crystals have attracted much attention over the past decades on account of the advantages of high specific surface area, high volume density and tunable pore sizes. These hierarchically ordered materials can be applied to various fields, such as filters, separation, chromatography, catalytic supports, sensors and photonic band gap structure. In this study, a highly ordered porous material incorporated with flow injection system was fabricated for tumor marker detection. The template concentration, surfactant concentration, drying temperature, the hybrid sol-gel reaction and surface modification reaction were investigate and optimized. Results showed that 2 wt% (w/w) polystyrene can be effectively used as a template to fabricate the highly ordered porous structures in the presence of 1 CMC Tween 20. After drying the opal structure at 60 °C, a hexagonally arranged opal structure by natural gravity was formed. The hybrid sol solution prepared with tetraethoxy silicate (TEOS) and methyltrimethosy silicate (MTMS) at pH 2 was then infiltrated into the interstitial voids between polystyrenes by spin-coating. The samples were aged at room temperature and were calcined at 550 °C for the removal of polystyrene. The amino-modified structures derived from soaking with 5% (3-aminopropyl)trimethoxy silicate (APTS) for 1 hour were incorporated with the flow injection system for biomedical detection. The flow rate of 50 μL/min to 20 min of flow time was used to detect the cancer biomarkers. The detection range of alpha-fetoprotein (AFP) was from 10 to 5000 ng/mL, which locating on the biomedical application range, while the detection of anti-Hepatitis B core antigen (anti-HBcAg) was 1 to 100 ng/mL. The detection limits of AFP and anti-HBcAg are 100 and 10 ng/mL, respectively. In conclusion, the approach developed in this study is simple, convenient, cheap and rapid. Results obtained in this study indicate the high potential application for biomedical detection of cancer biomarker.
12:15 PM - AA4.3
Polymer Vertically Emitting Distributed Feedback Laser for Label-free Biochemical Sensing.
Meng Lu 1 , Brian Cunningham 1 Show Abstract
1 Electrical and Computer Engineering, University of Illinois at Urbana Champaign, Urbana, Illinois, United States
A new type of optical biosensor based upon a vertically-emitting distributed feedback (DFB) laser has been demonstrated. The sensor represents a departure from conventional passive resonant optical sensors to improve sensor detection resolution with a high Q factor spectral output provided by the stimulated emission process while maintaining high sensitivity and wide dynamic range. In contrast to high Q factor passive optical resonators, the DFB laser biosensor actively generates its own narrowband high intensity output, which facilitates coupling of the excitation source and stimulated emission with the collection optics. The DFB laser cavity is comprised of a one-dimensional 2ndorder Bragg grating, fabricated from polymer materials by a nanoreplica molding technique, resulting in inexpensive devices that are single-use disposable. The low-cost large area fabrication method and the robust illumination/detection configuration make the DFB laser sensor a prospective method for high throughput biomolecule screening applications, such as those used in pharmaceutical discovery research. The polymer vertically emitting DFB laser sensor consists of a polyethylene-terephthalate (PET) substrate, a low refractive index polymer grating/cladding, a spin coated laser dye doped SU-8 layer, and a high refractive index titanium dioxide (TiO2) thin film. The light is confined and amplified in the SU-8 and TiO2 double layer. By controlling the thickness of this double layer, single mode laser operation was achieved. Adsorption of biomolecules onto the laser surface alters the emission wavelength of the laser, thereby permitting the kinetic adsorption of a protein polymer monolayer or the specific binding of small molecules to be quantified. The DFB laser biosensor chip is pumped by a frequency-doubled Nd:YAG laser (λ= 532 nm) and the resulting stimulated emission is monitored with a grating-based spectrometer. Optical excitation and DFB emission signals are both coupled to/from a bundled optical fiber. The fabricated laser exhibits stimulated emission within the 585-620 nm wavelength range with a linewidth as small as 0.09 nm. A bulk refractive index sensitivity of 99.4 nm per refractive index unit was found by measuring the laser wavelength shift response to different solvents applied to the surface. The dynamic detection of a monolayer protein polymer poly(Lys, Phe) adsorption and sequential deposition of multiple layers of charged polyelectrolyte were used to characterize the surface sensitivity, dynamic range, and spatial extent of the evanescent field. Furthermore, a protein A-human IgG assay shows the sensor’s capability to sustain stable antibody and to capture a highly affinity antigen. Results for specific capture of small molecule analytes with large immobilized proteins are presented to characterize the detection resolution of the sensor and detection instrument.
12:30 PM - AA4.4
Optical Ellipsometric Probing of Hydrogen Atoms-initiated Reactions of Thiols on Gold Surfaces Modifying Dynamics of SAMs Formation.
Giuseppe Bianco 1 , Giovanni Bruno 1 , Maria Giangregorio 1 , Pio Capezzuto 1 , Maria Losurdo 1 , Alessandra Operamolla 2 , Omar Hassan 2 , Gianluca Farinola 2 , Francesco Babudri 2 , Francesco Naso 2 Show Abstract
1 PlasmaChemistry, IMIP-CNR, Bari Italy, 2 Dept Chemistry, University f bari, Bari Italy
Biorganic functionalization of gold thin films and nano cluster mesoscalar assemblies and their resulting optical properties have immense applications ranging from biosensing to nano medicine. The appealing properties are in the surface plasmon resonance of those bio-metal ensembles that can be tailored not only by the gold nanoclusters geometry but also by the nature of the ligating molecules and by the chemistry of the interface. This characteristic is being exploited for realizing nanoscale optical biosensors based on localized surface plasmon resonance of noble metal nanoparticles. In spite of the fact that a significant level of understanding of the formation, aggregation and properties of self-assembled-monolayers (SAMs) has been gained, the detailed mechanism of their formation and how this depends on the structure of the functionalizing molecule is still not fully understood. Specifically, using thiols SAMs, the charge transferred during the SAM formation dictating its geometry and the fate of hydrogen atoms are unclear.In this contribution we discuss the surface chemistry and kinetics and dynamics of interface phenomena playing a role during functionalization of gold nanoparticles supported on Si(100) substrates with novel synthetised organic dithiols. Specifically, we use the (4”-methoxy-1,1’,4’,1”-terphenyl-3,5-diyl)dimethanethiol (4MeO-TPDMT) as a model system to discern electric-charge transport phenomena from simple geometry-related phenomena, since molecules containing aromatic rings are characterized by a greater ability to transport charge than aliphatic thiols. We present data on the effect of various experimental parameters including Au nanoparticles size and density, Au nanoparticles and thin films treatments (e.g. by H2 plasmas), and temperature of functionalization on the thiol self-assembled-monolayer (SAM) formation dynamic and on the resulting layer morphology, thickness and optical properties. This study not only provides an insight into the collective behavior of the functionalized Au nanoparticles but also give light on the nature of interaction of aromatic and aliphatic thiols with Au surfaces. In particular, the role and fate of hydrogen atoms during functionalization is elucidated by treatments of Au thin films and nanoparticles with atomic hydrogen plasmas and investigating how this interface modification affects the dynamics of the SAM formation. This investigation is performed by exploiting spectroscopic ellipsometry (UVISEL, Jobin Yvon) for the optical monitoring of the modification of the Au surface plasmon resonance during all the various processing. It is demonstrated that a different SAM geometry characterize the aromatic dithiol also depending on the atpomic hydrogen treatments of the Au surface and this has also consequencies on the subsequent anchoring of other molecules active in sensing. The optical data are corroborated by atomic force microscopy.
12:45 PM - AA4.5
Fabrication of Sub-micron Periodic Metallic Structures for Surface Plasmon Resonance Sensing.
Yi Lou 1 , John McGlade 1 , Anuj Dhawan 1 , John Muth 1 Show Abstract
1 Electrical and Computer Engineering, North Carolina State University, Raleigh, North Carolina, United States
The enhanced transmission of light through periodic arrays of sub-micron metallic apertures provides a novel approach for the detection of bio-molecules and other sensing applications. In the transmission spectrum, the light passing though these patterned metallic films is very sensitive to the surface environment since the excitation of the surface plasmon polariton modes is a resonance phenomenon sensitive to the variations in the dielectric constant of the local environment. Traditionally, the surface patterns are made by Focused Ion Beam (FIB) milling; however, the high cost constrains its application in bio-imaging studies. In this study, we have developed a low cost method of fabricating large area, well patterned periodic structures on 180 nm thick gold films. Nanosphere Lithography (NSL) has been used to lay down hexagonally packed colloidal spheres (600 nm in diameter) on the substrate by a directed self-assembly process. The samples undergo a reactive ion etching process to reduce the sphere diameter to the desired size. Subsequently, a layer of metal is deposited followed by chemical solvent removal of the spheres to obtain the periodical surface structure. The transmission spectrum collected from both FIB milled and NSL patterned samples are compared under both differently polarized light and surface environments. In addition, we show that these sensors can be integrated into lab-on-a-chip type systems by incorporating the sensor into a microfluidic channel.
AA5: Fluorescense-based Biosensors
Tuesday PM, December 02, 2008
Gardner A/B (Sheraton)
2:30 PM - **AA5.1
Integrated High Performance Fluorescent Microarray Systems by Controlling Spontaneous Emission.
Claude Weisbuch 1 2 Show Abstract
1 lab pmc, ecole polytechnique CNRS, Palaiseau France, 2 materials department, UCSB, Santa Barbara, California, United States
Although they offer the best sensitivity among biosensing techniques, fluorescent DNA or protein microarrays suffer from a poor luminescence efficiency. Fluorescent spots originate from the spatially selective attachment of fluorescent species on glass surfaces, but they mostly emit into the substrate, and the remaining light is poorly collected for detection. We will describe amplifying substrates, integrated CCD/biochips and evanescent wave excitation systems which lead to greatly enhanced fluorescence collection, translating into economies of biological material, improved detection of genes with low expression, real-time measurements of hybridization, all achieved in high-functionality integrated systems.Amplifying fluorescence from species close to a substrate can be obtained with multilayer dielectric mirrors. For proper design , interferences enhance both fluorescence excitation and collection, each about four fold. The overall increase reaches 10 to 15 fold as compared to a standard glass slide. Such improvements together with directionality of emission allow large area imaging in turn allowing to perform real-time hybridization measurements .The optical signal to noise ratio is still limited by various factors, among which the capture efficiency. Taking advantage of a very high rejection filter directly deposited onto a silicon arrayed detector (CMOS or CCD), it is demonstrated that a highly miniature lens-free assay with photon capture of order unity operates with a 30-fold performance improvement over a conventional imaging scheme. A single molecule per pixel sensitivity is predicted and its impact for useful real-time and end-point assays is discussed.Probing microarray assays in the presence of hybridization mix retrieves precious biological information, especially on hybridization kinetics with immobilized species. However in common fluorescent detection schemes, the hybridization signal is obscured by the high supernatant background. A solution consists in selectively exciting the microarray surface with evanescent fields, using planar optical waveguides. We show that this configuration also presents another advantage: a strong enhancement of the exciting field. Model calculations and experimental measurements on biological species show that this enhancement can exceed 10 000 for optimal waveguides.All these systems rely on designing and fabricating demanding optical structures: wideband reflectors, ultra-high rejection selective filters, wavelength-converting waveguides, etc., often at materials limits which will be discussed.1.H. Choumane et al., Appl. Phys. Lett. 87, 031102 (2005)2. J. C. Avarre et al., BioTechniques, 44, pp 913-920 (June 2008)3. L. Martinelli et al., Appl. Phys. Lett., 91, 083901 (2007)4.G. Sagarzazu, submitted.
3:00 PM - **AA5.2
Optical Modulation of Single Walled Carbon Nanotubes for Life Science and Biomedical Applications.
Michael Strano 1 Show Abstract
1 Department of Chemical Engineering, MIT, Cambridge, Massachusetts, United States
Nanoscale sensing elements offer promise for single molecule analyte detection in physically orbiologically constrained environments. Molecular adsorption can be amplified via modulation of sharp singularities in the electronic density of states that arise from 1D quantum confinement1. Single-walled carbon nanotubes (SWNT), as single molecule optical sensors2,3, offer unique advantages such as photostable near-infrared (n-IR) emission for prolonged detection through biological media, single-molecule sensitivity and, nearly orthogonal optical modes for signal transduction that can be used to identify distinct classes of analytes. Selective binding to the SWNT surface is difficult to engineer4. In this lecture, we will briefly review the immerging field of fluorescent diagnostics using band gap emission from SWNT. In recent work, we demonstrate that even a single pair of SWNT provides at least four optical modes that can be modulated to uniquely fingerprint chemical agents by the degree to which they alter either the emission band intensity or wavelength. We validate this identification method in vitro by demonstrating detection and identification of six genotoxic analytes, including chemotherapeutic drugs and reactive oxygen species (ROS), which are spectroscopically differentiated into four distinct classes. We also demonstrate single-molecule sensitivity in detecting hydrogen peroxide, one of the most common genotoxins and an important cellular signal. Finally, we employ our sensing and fingerprinting method of these analytes in real time within live 3T3 cells, demonstrating the first multiplexed optical detection from a nanoscale biosensor and the first label-free tool to optically discriminate between genotoxins. We will also discuss our recent efforts to fabricate biomedical sensors for real time detection of glucose and other important physiologically relevant analytes in-vivo. The response of embedded SWNT in a swellable hydrogel construct to osmotic pressure gradients will be discussed, as well as its potential as a unique transduction mechanism for a new class of implantable sensors. 1. Saito, R., Dresselhaus, G. & Dresselhaus, M. S. Physical Properties of Carbon Nanotubes (Imperial College Press,London, 1998). 2. Barone, P. W., Baik, S., Heller, D. A. & Strano, M. S. Near-Infrared Optical Sensors Based on Single-Walled CarbonNanotubes. Nature Materials 4, 86-92 (2005).3. Jeng, E. S., Moll, A. E., Roy, A. C., Gastala, J. B. & Strano, M. S. Detection of DNA hybridization using the near infrared band-gap fluorescence of single-walled carbon nanotubes. Nano Letters 6, 371-375 (2006).4. Heller, D. A. et al. Optical detection of DNA conformational polymorphism on single-walled carbon nanotubes.Science 311, 508-511 (2006).
3:30 PM - **AA5.3
High Throughput Optical Mapping of Single DNA Molecules in a Microfluidic Environment.
Jeffrey Krogmeier 1 , Ian Schaefer 1 , Douglas Cameron 1 , Jonathan Larson 1 , Rudolf Gilmanshin 1 Show Abstract
1 , U.S. Genomics, Woburn, Massachusetts, United States
4:00 PM - AA5.4
Self-luminescent Microdisk of Tb3+ Doped Silicon Oxy-nitride for Biosensor Applications.
Hoon Jeong 1 , Jung H. Shin 1 , Gun yong Sung 2 Show Abstract
1 Physics, Korea Advanced Institute of Science and Technology, Daejeon Korea (the Republic of), 2 Bio-photonic devices team (IT Convergence and Component Lab), ETRI, Daejeon Korea (the Republic of)
A great interest lies on bio-sensors based on optical micro-resonators, such as microdisk or microsphere, which have whispering-gallery modes (WGMs) for obtaining high sensitivity and size reduction. A bio-molecule which is adsorbed onto the surface of the resonator can change the effective size and/or the refractive index of the resonator and this change is the foundation for WGM frequency-shift biosensor. In most cases, however, measuring the shift in the resonance frequency requires complex and delicate optical setups including tapered fibers or waveguides to couple light from a highly tuned laser in and out of the microcavity. It not only greatly increases the complexity of the device, making it bulky, but also the cost due to the need to finely control the pump beam in signal coupling. A simpler approach is to use a microdisk made of self-luminescent material. In such a case, the shift in the resonance wavelength can be measured simply by directly observing of the WGM emission. In this paper, we design, and fabricate a green, self-luminescent Tb3+ doped silicon oxy-nitride (SiOxNy) microdisk, and evaluate its performance for biosensor applications. SiOxNy is widely used in CMOS industry, and is compatible with most Si-based processes. Furthermore, it has a high refractive index and good chemical selectivity against silica, making mass-fabrication of compact devices feasible. More importantly, WGM in a Tb3+ doped SiOxNy microdisk can be excited easily by a low-cost external light source such as UV-LED in a top-pumping configuration due to energy transfer from the host matrix to the Tb3+ ions. Another important advantage of Tb-doped SiOxNy is its strong luminescence in the green range due to the Tb3+ ions. As the absorption coefficient of Si in the green region is much larger than the near-IR region which is the typical luminescence range of other Si-based light-emitting devices such as Si nanoclusters, such a green-luminescing microdisk resonator is expected to be more advantageous for realization of a compact, all-Si ‘lab-on-a-chip’ devices. Using finite-difference time domain (FDTD) simulations, we found that a 10 μm diameter Tb3+ doped silicon oxy-nitride microdisk can, in principle, have a Q factor of 1.4×106 and sensitivity of 9.7×10-7 RIU. This value is higher than present commercial biosensors and comparable with the values of the reported sensitivity of biosensors with microsphere, microring, and surface plasmon interferometer. Actual fabrication of microdisks were done using electron beam lithography of Tb-doped SiOxNy film deposited by PECVD, followed by a chemical etching to form a pedestal structure. The Q factor of the disk, measured by observing the WGM emission with the side-PL setup, was 220. The estimated the sensitivity is 7.0×10-3 RIU. Possibility of obtaining a much higher Q-factors and sensitivity with improved fabrication condition will be discussed.
4:15 PM - AA5.5
Carbon Nanotube Biosensors for Multi-modal Detection of Genotoxic Agents.
Daniel Heller 1 , Michael Strano 1 Show Abstract
1 Department of Chemical Engineering, Massachusetts Institiute of Technology, Cambridge, Massachusetts, United States
Complexes of single-walled carbon nanotubes and DNA, formed by individually encapsulating nanotubes with oligonucleotides, detect genotoxic agents in real-time. The sensing occurs via multiple optical modes, giving each analyte a distinct signature. Single-walled carbon nanotubes emit near-infrared fluorescence and exhibit environmental sensitivity. By their encapsulation in short strands of synthetic DNA, we introduce a selective handle for changes in the nanotube emission which responds to agents that react with DNA. The complexes detect DNA-damaging reactive oxygen species (ROS) and chemotherapeutic drugs via red-shifts in emission energy up to 60 meV as well as optical quenching, The nanotube-DNA complexes are internalized into mammalian cells via endocytosis, without exhibiting cytotoxic effects, and emit from within live tissues. Upon introducing alkylating agents and oxidative species, the complexes transduce analyte activity information in situ. This platform is being developed as a research and diagnostic tool for free radical biology, drug discovery, and pharmacodynamics.
AA6: Surface Sensing
Tuesday PM, December 02, 2008
Gardner A/B (Sheraton)
4:30 PM - AA6.1
Direct Write Electron Beam Patterning of DNA Thin Films and Related Applications.
Andrew Steckl 1 , Robert Jones 1 , Weixin Li 1 , Hans Spaeth 1 Show Abstract
1 Nanoelectronics Laboratory, University of Cincinnati, Cincinnati, Ohio, United States
Interest in using the unique properties of DNA has grown rapidly in the areas of bioelectronics and photonic device applications. Several properties and processing characteristics are required in order for DNA materials to be usefully incorporated into devices. These include the formation of functional complexes and thin/thick films, ability to pattern the films, and incorporation of the patterns into device structures. We have previously demonstrated the ability to form well characterized DNA complexes in solution and to form thin films with predictable properties by spin coating. In addition, we have demonstrated the use of DNA thin films in high performance optical waveguides, organic light emitting diode and optically pumped laser applications. To date, several indirect techniques such as charge trapping, molecular lift-off, or surface functionalization have been reported for obtaining DNA nano- and micro-scale features. In these patterning techniques, the DNA thin film is patterned by either the topography or the surface modification of the underlying material. Given the interest in DNA-based devices and material applications at the micro- and nano-scale (such as quantum wires, biosensors, and others) it is important to develop techniques for fine feature patterning of the DNA material.We report on the first use of direct write electron beam lithography (DW-EBL) patterning of DNA-based materials. Water insoluble and organic solvent soluble DNA:CTMA complexes were formed by reaction of DNA polymers with cationic surfactants and other molecular species. Thin films with thicknesses ranging from 85 to 300 nm were prepared by spin coating. DW-EBL was conducted using a Raith 150 system. The resulting exposed areas demonstrated either positive or negative resist properties depending on development solution. The characteristics of DNA:CTMA material as a patternable electron sensitive resist medium are presented for different exposure conditions (10-30kV), development conditions, structure size (100nm-20µm), and structure complexity. Contrast values of ~ 2 have been obtained in both positive and negative resist modes. Both simple (20 µm diameter circle and square) and complex (Fresnel lens) patterns with nanometer scale features (< 100 nm) in DNA films are possible using this method. Device structures utilizing DW-EBL patterning will be described.
4:45 PM - AA6.2
Development of a Self-Cleaning Membrane for Implantable Glucose Biosensors.
Rebecca Gant 1 , Yaping Hou 1 , Gerard Coté 1 , Melissa Grunlan 1 Show Abstract
1 Biomedical Engineering, Texas A&M University, College Station, Texas, United States
Optically based biosensors are advantageous because after initial implantation, they have the potential for continuous, non-invasive detection of an analyte such as glucose. However, glucose diffusion and hence sensing is often compromised by the attachment and accumulation of cells from surrounding tissue as part of the host response. As a result, the sensor must be removed and replaced. The focus of this work is the development of a self-cleaning sensor membrane material which undergoes cyclical, thermally driven removal of adhered cells to improve the efficacy and lifetime of an implanted glucose biosensor. Thus, we prepared novel thermoresponsive nanocomposite hydrogels comprised of a poly(N-isopropylacrylamide) (PNIPAAm) hydrogel matrix and variable levels of polysiloxane colloidal nanoparticles (average diameter = 220 nm). PNIPAAm hydrogels are known to become more hydrophobic when they reversibly switch from a water-swollen to a shrunken (deswollen) state at temperatures above the volume phase transition temperature (VPTT) of ~33 ○C. The resulting temperature-activated physical and surface property changes disrupt the adhesion of adsorbed cells. The VPTT of the nanocomposite hydrogels was unaltered compared to that of pure PNIPAAm hydrogels which is conveniently near physiological temperature. Mechanical analyses revealed that higher nanoparticle content generally produced improved hydrogel mechanical properties. As the amount of hydrophobic polysiloxane nanoparticles was increased, surfaces of nanocomposite hydrogels became increasingly more hydrophobic at all temperatures between 10 and 40 ○C. Temperature-regulated detachment of GFP-H2B 3T3 fibroblast cells from and diffusion of glucose through nanocomposite hydrogels containing 1 wt% nanoparticles, both with and without introduction of additional poration, was compared to that of a non-thermoresponsive poly(ethylene glycol) hydrogel.
5:00 PM - AA6.3
Optical Sensors for Biomolecules Based on Liquid Crystals.
Nicholas Abbott 1 Show Abstract
1 Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, United States
This presentation will describe the use of surface-induced ordering transitions in liquid crystalline materials to report the presence and activity of biomolecules at interfaces. The presentation will focus on two examples, each addressing a class of molecules that is biomedically important. The first example will focus on label-free and multiplexed methods that employ liquid crystals to report proteins captured by surface-immobilized binding groups. The approach is general, and will be demonstrated to be compatible with oligopeptide-, nucleic acid aptamer- and antibody-mediated capture of proteins. A particular focus will be directed to the use of liquid crystals to report the expression levels and phosphorylation status of the membrane protein, the epidermal growth factor receptor (EGFR). Over-expression and mutation of the EGFR has been associated with some of the most aggressive and incurable cancers. Results will be presented to demonstrate that ordering transitions in liquid crystals can be used to identify tyrosine kinase inhibitors of the EGFR. The second example to be presented in the talk will revolve around the capture and identification of glycolipids, including GM1. Dynamic ordering transitions in liquid crystals that are driven by the assembly of glycolipids at aqueous-LC interfaces will be discussed. Potential applications of liquid crystal-based materials for sensors for biomolecules with high medical relevancy will be discussed.
5:15 PM - AA6.4
Direct, Detergent-Free Transfer of Cell Membranes to a Solid Support.
Morgan Mager 1 , Nicholas Melosh 1 Show Abstract
1 Materials Science, Stanford University, Stanford, California, United States
Much of the molecular machinery that controls intercellular signaling is located on or within the lipid bilayer that comprises the cell membrane. These integral membrane proteins could provide valuable functionality to future biosensors, but must first be integrated with an inorganic platform. Traditionally, this process has relied on detergent- or solvent-mediated extraction of membrane components, followed by re-insertion into a supported bilayer. Such procedures are not only time and labor intensive, but also disrupt and denature many of the delicate molecules being transferred. We present a direct and single-step method to transfer lipid membranes from the cellular surface to a solid support. By “inking” these membranes onto an air bubble, we are able to directly deposit them on a surface using bubble collapse deposition (BCD). This process can be used to deposit pure natural membranes, or to mix these cellular components into an artificial planar bilayer. Both the pure and mixed membranes retain lateral fluidity, a key indicator of high quality supported bilayers. We also examine which classes of membrane proteins are transferred along with the membrane lipids and under what conditions these proteins retain their functionality. By transferring membrane components from the 3D cell surface to a 2D inorganic substrate, this technique allows the fabrication of arrayed biosensors based on surface-sensitive characterization methods.
5:30 PM - AA6.5
Llama Derived Single Domain Antibody Templated Gold Nanoparticles for Sensing.
Joseph Slocik 1 , Ellen Goldman 2 , Jinny Liu 2 , Rajesh Naik 1 Show Abstract
1 Materials and Manufacturing Directorate, Wright Patterson AFB, Wright-Patterson AFB, Ohio, United States, 2 Center for Bio/Molecular Science and Engineering, U.S. Naval Research Laboratory, Washington , District of Columbia, United States
5:45 PM - AA6.6
Robust Sensing Films: The Bio-Inorganic Interface.
Aaron Anderson 1 , Andrew Dattelbaum 2 , Gabriel Montano 2 , Victoria Hansen 1 , Dominique Price 1 , Harshini Mukundan 1 , Jurgen Schmidt 3 , Wynne Grace 1 , Jennifer Martinez 2 , Karen Grace 4 , Basil Swanson 1 Show Abstract
1 Physical Chemistry & Applied Spectroscopy, Los Alamos National Laboratory, Los Alamos, New Mexico, United States, 2 Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Los Alamos, New Mexico, United States, 3 Advanced Measurement Science, Los Alamos National Laboratory, Los Alamos, New Mexico, United States, 4 Space Instrumentation Systems, Los Alamos National Laboratory, Los Alamos, New Mexico, United States
In our efforts toward biosensor development, we have relied on phospholipid bilayers as the interface between the analyte and the transducer. Phospholipid bilayers offer superior resistance to non-specific binding, but have several limitations, including instability to air or detergents and degradation upon prolonged storage. To overcome these disadvantages, we have developed covalently-bound, aminopropylsilane-based, polyethylene glycol (PEG)-modified, self-assembled thin-films (SAMs) for biological detection on either planar or spherical substrates. The preparation and characterization of these thin films, as well as their validation against B. anthracis protective antigen (PA), will be shown. This presentation will also discuss the use of these thin films against a variety of other targets including carcinoembryonic antigen (breast cancer), several tuberculosis markers in urine, and influenza. Finally, a brief, albeit general, overview of potential improvements to our thin-films will be discussed, including changes to the length of the alkyl chain, the connecting bond between the PEG- and alkyl chain portions, and the functional terminus of the SAM. Through these modifications, we envision building a set of SAM precursors from which we can design an ideal surface for sensing, depending on the target and its unique requirements.
AA7: Poster Session
Wednesday AM, December 03, 2008
Exhibition Hall D (Hynes)
9:00 PM - AA7.1
Plasmonic Resonance for Improved Spontaneous Emission of a Nano-fluorophore in Metal Nanoshells.
Wallace Choy 1 , X. Chen 1 2 , Sailing He 2 , P. Chui 1 Show Abstract
1 Department of Electrical & Electronic Engineering, the University of Hong Kong, Hong Kong China, 2 Centre for Optical and Electromagnetic Research, Zhejiang University, Hangzhou China
9:00 PM - AA7.11
Near-field Through-Space Förster Resonance Energy Transfer Between CdSe/CdS/ZnS Core/Shell Nanocrystals and Cy5 Dyes.
Wonjung Kim 1 , Sung Jun Lim 1 , Yongwook Kim 1 , Hye-Joo Yoon 1 , Seung Koo Shin 1 Show Abstract
1 Biotechnology Center, Department of Chemistry, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea (the Republic of)
We have studied through-space Förster resonance energy transfer (FRET) between 620-nm emitting CdSe/CdS/Zns nanocrystal donor and Cy5 dye acceptor at near-field. A flat tip end with 400-nm aperture was obtained by focused ion beam milling of a tapered optical fiber used for near-field scanning optical microscopy (NSOM). A monolayer of primary amines was fabricated on the NSOM tip as well as on a glass substrate by aminosilanization. A monolayer of Cy5 dyes was conjugated onto the surface of the NSOM tip and a monolayer of CdSe/CdS/ZnS nanocrystals was conjugated onto the surface of the glass substrate by amide bond coupling. Using NSOM, the Cy5 bound tip was approached to the glass substrate by 1–10 nm steps. The fluorescence spectra from FRET pairs and the fluorescence lifetime decay of energy donor nanocrystals were measured simultaneously as a function of the tip-to-sample distance. When the tip-to-sample distance became less than 10 nm, FRET occurred. The effective Förster radius of the CdSe/CdS/ZnS nanocrystal-Cy5 dye FRET pair was precisely determined from the changes of the fluorescence intensity of FRET pairs and the fluorescence lifetime decay of energy donor as s function of the tip-to-sample distance.
9:00 PM - AA7.13
Interplay Between Surface Chemistry and Optical Behavior of Semiconductor-biomolecule Functionalized Sensing Systems: An Optical Investigation by Spectroscopic Ellipsometry.
April Brown 1 , Maria Losurdo 2 1 , Scott Walter 1 , Michelari Giangregorio 2 , Michael Angelo 1 , William Lampert 3 , Giovanni Bruno 2 Show Abstract
1 ECE Dept, Duke University, Durham, North Carolina, United States, 2 PlasmaChemistry, IMIP-CNR, Bari Italy, 3 , US Army Research Office, Research Triangle Park, North Carolina, United States
Biochemical functionalization of semiconductor –based sensors is of interest for defense, biological and environmental sensing applications. By investigating a number of semiconductor based systems with a gap ranging in the broad interval from 0.4 eV (InAs) to 3.4 eV (GaN), we demonstrate for the first time the correlation existing between the sensing activity and the semiconductor gap. This correlation might be useful to choose the appropriate semiconductor-based platform for a target sensing application.Semiconductors surfaces have been functionalized with bovine and human albumin and with porphyrins.For such semiconductor-biomolecule based sensors, the degree of coverage, the aggregation, the type of binding and orientation of bio-molecules on the semiconductor surface is important for the sensing activity. In this frame, this contribution presents a comparative analysis of the chemistry and kinetics of the functionalization with bio-molecules and proteins of various semiconductors including Si, SiC and various III-V such as InAs, InP, GaAs and GaN. As first step of the investigation we discuss the effect of various experimental parameters such as concentration of functionalizing solutions, dipping time and mainly the impact of the status of semiconductor surfaces and their modification by chemical treatments (e.g. native oxide, chemical wet treatments and passivating processes, whose role is pre-conditioning the surface with –H or –NH terminal groups) on the self-assembling of functionalizing biomolecules. As second step, the optical behavior of those semiconductor/biomolecule systems is investigated exploiting real time spectroscopic ellipsometry(UVISEL-JY operating in the 0.75eV-6.5eV). As final step, implementation by coupling semiconductor with metal (Au, Ga) nanoparticles and functionalizing the nanoparticles by porphyrins and their optical activity exploiting the surface plasmon resonance monitored by spectroscopic ellipsometry is presented.This study makes significant strides in understanding and controlling semiconductors surface functionalization for sensor exploiting optical surface sensitive techniques such as spectroscopic ellipsometry (SE) to determine the interplay existing between surface chemistry, functionalization coverage/thickness and optical behavior.
9:00 PM - AA7.14
MEH-PPV Based Blue-light Dosimeter for Hyperbilirubinemia Treatment.
Pedro Autreto 1 , Claudia Vasconcelos 2 , Marcelo Flores 1 , Douglas Galvao 1 , Rodrigo Bianchi 2 Show Abstract
1 , State University of Campinas, Campinas/SP, São Paulo, Brazil, 2 , Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil
The neonatal hyperbilirubinaemia, or jaundice, is one of the most commonly problem found in practice of the Neonatology, and reaches approximately 80% of newborns. The irradiation using Ultra Violet lamps is the most used treatment to avoid its complications, which can cause irreversible neurological lesions if left untreated. In poor nations this problem is aggravated by the non-existence of appropriated regulations and effective inspection to assure that the visible and UV lamps are providing the proper amount of blue-light radiation. Thus, the construction of low cost and reliable dosimeters can be an effective tool to treat and even save lives of newborns. In this work we report the fabrication and characterization of one of this kind of dosimeter (cost less than US$ 0.50) based on the use of poly(2-metoxy-5(2'-ethylhexyloxy)-p-phenylenevinylene) (MEH-PPV) solutions. We exploited the light induced polymer degradation and associated luminescent properties to design a novel blue-light phototherapy dosimeter. MEH-PPV photoluminescence (PL) measurements were carried out for solutions under the effect of blue LED light source (460 nm focus). All measurements were performed trying to reproduce the clinical environmental conditions for the irradiation treatments. It is observed changes from orange-red to yellow clearly, while its peak position emission shifts from orange-red (lmax = 571 nm) to green (lmax = 450 nm) and decreases in intensity with the radiation exposure time. Experiments performed with oxygen enriched solutions were shown to improve these effects, which are believed to be caused by the replacement of vinyl double bonds by carbonyl groups in the polymer backbone. Analyses of the relationship between the radiation doses and the changes MEH-PPV color solutions can be used to calibrate the indicator-dosimeter. We have also investigated theoretical models for the MEH-PPV photodegradation based on structural models for MEH-PPV oligomers, in vacuum and solvated (chloroform). We investigated as the addition of oxygen and removal of vinyl double bonds affect the absorption and emission spectra . The calculations were carried out using the semi-empirical molecular orbital method PM3 (Parametric Method 3) within COSMO methodology (conductor like screening model) to treat solvent effects. Zerner’s intermediate neglect of differential overlap (ZINDO S1) was used to simulate the absorption/emission spectra. In order to obtain a good description of oligomers structure, all torsions, angles and bond lengths were fully optimized. The theoretical results are in excellent agreement with the experimental data if we assume that the incorporation of carbonyl group is associated with the major photodegradation processes.
9:00 PM - AA7.15
Top-Down Approach to the Fabrication of GaN-Based Photonic Crystal Biosensor.
B. Hamza 1 , R. Tompkins 2 , J. Nightingale 1 , S. Yeldandi 1 , T. Yarber 3 , H. Yalamanchili 1 , H. Andagana 1 , L. Rodak 1 , J. Dawson 1 , X. Cao 1 , L. Hornak 1 , D. Korakakis 1 4 Show Abstract
1 Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, West Virginia, United States, 2 Department of Physics, West Virginia University, Morgantown, West Virginia, United States, 3 Industrial Engineering Department, Albany State University, Albany, Georgia, United States, 4 , National Energy Technology Laboratory, Morgantown, West Virginia, United States
9:00 PM - AA7.16
Optical Discs for Plasmonic Applications: From Plasmon Resonance Biosensors to Doubly Resonant Infrared Sensing.
Ozlem Senlik 1 , Hasan Guner 1 , Kemal Gurel 1 , Burkan Kaplan 1 , Mehmet Bayindir 1 2 , Aykutlu Dana 1 Show Abstract
1 Institute of Materials Science and Nanotechnology, Bilkent University, Ankara Turkey, 2 Department of Physics, Bilkent University, Ankara Turkey
We present a simple method to convert optical discs (CD, DVD and Blu-Ray) into a geometry suitable for studying grating coupled plasmon resonance based effects. Grating coupled plasmon resonance (GCPR) is a simple and powerful way to observe many plasmonic effects, however to observe sharp resonances the depth and period of corrugations must lie within a restricted range of values. The optical discs have a corrugated imprinted surfaces protected by external coatings. By exposing the surfaces, simple chemical procedures can be used to tune the surface corrugation depth to optimal geometries for sharp and deep resonant absoption peaks. Resulting substrates provide a valuable platform for study of plasmon physics. We present topographic profiles on optical discs with different groove depths (due to different processing parameters) and using atomic force microscopy we analyse the fourier components of surface topography, which is important in determination of plasmonic properties. Theoretical analysis of such devices are carried out using analytical approximations and rigirously coupled wave analysis. Using substrates prepared by processing commercially available optical discs, we present experimental data on sharp plasmon resonances in air and in water , with peak wavelengths ranging from 270 nm to 2.9 micrometers. We demonstrate use of optical discs for GCPR biosensors in a simple setup. Another example application is presented where optical discs are used for plasmon enhanced transmission in periodic structures. Such filters based on optical discs are demonstrated to have up to 20% polarized transmission and can be tuned from UV to mid-infrared (IR), with full widths at half maxima of about 5 nm in the visible and about 50 nm around 3 micrometers. The center wavelength can be tuned by simply changing the angle of incidence. The filters provide a simple means of obtaining narrow-band tunable light sources from near UV to mid-IR and are very appropriate for spectroscopic applications. We also discuss the sensitivity enhancement in grating coupled plasmon resonance sensors using Blu-Ray discs at a wavelength around 300 nm for doubly resonant DNA sensors. We show that such doubly resonant sensors, i.e. sensors operating by using plasmon resonances excited at the absorption resonance of molecules to be sensed, provide sensitivity enhancement of about an order of magnitude for DNA sensing. However, using such doubly resonant sensors at near and mid-infrared wavelengths, we predict that higher enhancements are possible. Finally we demonstrate micromechanical angular deflection detection based biosensing simultaneously with plasmon resonance biosensing using optical discs as starting substrates.
9:00 PM - AA7.17
Aperiodic SERS Substrates.
Ashwin Gopinath 1 , Svetlana Boriskina 1 , Bjoern Reinhard 2 , Dal Negro Luca 1 Show Abstract
1 Electrical and Computer Engineering, Boston University, Boston, Massachusetts, United States, 2 Chemistry, Boston University, Boston, Massachusetts, United States
9:00 PM - AA7.18
Investigation of Steady State and Time-dependent Luminescence Properties of Colloidal InGaP Quantum Dots.
Subhasish Chatterjee 1 3 , Nikesh Valappil 3 , Vinod Menon 2 3 Show Abstract
1 Chemistry , The Gradaute Center of CUNY, New York, New York, United States, 3 Physics , Queens College, CUNY, Flushing, New York, United States, 2 Physics , The Graduate Center of CUNY, New York, New York, United States
9:00 PM - AA7.2
Surface-Enhanced-Raman-Scattering on Quartz Substrate and Optical Fiber with Nanostructures Fabricated by Femto-Second Laser.
Wenhui Wang 1 , Haibin Huo 2 , Xiaodong Ma 1 , Xingwei Wang 1 , Mengyan Shen 2 Show Abstract
1 Electrical and Computer Engineering, University of Massachusetts Lowell, Lowell, Massachusetts, United States, 2 Physics Department, University of Massachusetts Lowell, Lowell, Massachusetts, United States
Raman spectrum is a technology that can detect and distinguish materials based on the molecular related Raman Scattering. However, the signal is usually too weak to be detected. The Raman spectrum signal can be enhanced by surface roughing. Many methods have been used to introduce the rough surface to the substrate, including chemical etching, photolithography, chemical synthetic nano-particles and femto-second laser assisted machining, etc. However, these methods are not suitable for all Surface-Enhanced-Raman-Scattering SERS applications and researchers are still engaged in the development of new method and its applications. Femto-second (fs) laser has extremely high peak power. Therefore, it can be used to machine materials that are difficult to handle by traditional methods. Quartz and fused silica have unique optical, chemical and thermal properties and have been widely used in optical communication and sensing field. Femto-second laser has been used in fabrication of optical devices, nanosurgery, material processing, micro-fluidic devices on the transparent materials such as glass and fused silica. We developed a novel method to fabricate nanometer size features on glass, fused silica and quartz substrate. The principle is using fs laser to sputter the transparent materials and deposit them near the laser spot when they are cooled down. Nano-features on optical materials can make the optical sensing system design easier and more flexible. For example, the optical fiber with SERS sensor at the tip can be used in remote sensing as well as applications where space is restricted and the traditional SERS probes can not reach. Scanning Electron Microscope SEM photos of the structures fabricated on quartz substrate and optical fiber show that features of the size less than 100 nm have been fabricated. The substrates were then coated with about 20 nm silver. Rhodamine 6G was tested using these substrates by a Raman spectrometer (R3000, Raman Systems). Raman spectrum signals show that the strength of the Raman scattering was greatly enhanced compared to those substrates without nanofeatures.
9:00 PM - AA7.3
Optical Properties of Rod-like Metallic Nanostructures: Insight from Theory and Experiment.
Jinsong Duan 1 , Kyoungweon Park 1 , Robert MacCuspie 1 , Richard Vaia 1 , Ruth Pachter 1 Show Abstract
1 , AFRL, Wright-Patterson AFB, Dayton, Ohio, United States
In order to understand the parameters that affect the local surface plasmon resonance of complex metal nanostructures, for achieving desired properties for a specific functionality, we have studied theoretically the optical properties of Au and Ag nanorods, as well as core-shell Au-Ag nanorod-like structures, which we carefully characterized experimentally. In our systematic theoretical investigation, we examined the effects of geometrical definition and composition of an Au-Ag core-shell structure, the dielectric function applied, and also the effects of changing the surrounding media. Calculated results agree well with available experimental values, and insight is provided into changes of the optical properties upon core-shell structure formation. For example, it was calculated that the optical extinction is initially red-shifted, and thereafter blue-shifted, as an Au Ag-tipped nanorod is transformed into a well-defined fully coated Au-Ag core-shell structure with a different aspect ratio. Details on the effects of changing the refractive index of the medium and using a realistic dielectric function will be discussed in detail.
9:00 PM - AA7.4
Graphened IR Screens: A New Platform for Bio-Detection.
Amrita Banerjee 1 , Dieter Moeller 1 , Haim Grebel 1 Show Abstract
1 ECE, New Jersey Institute of Technology, Newark, New Jersey, United States
Metallo-dielectric screens have been investigated from the visible to the THz spectral region for astronomy and remote sensing applications. These screens are made of periodic structure, which is at resonance with the IR wavelength of interest. A standing wave of surface charges is formed at resonance conditions, which enables transmission or, reflection of certain IR bands. Graphene is a monolayer thick crystal of carbon. Graphene is chemically inert and exhibits very large mobility values. Recently, we succeeded in fabricating mono and a few-layered graphene into films on solid and perforated substrates. By combining the resonance properties of IR screens and graphene we hope to fabricate new spectroscopic platforms, which enhance IR and Raman signals of molecules and specifically, bio-species.Raman spectroscopy is widely used spectroscopic tool to detect molecular vibrations. Raman signals are typically weak and many attempts have been made to enhance these signals. We hypothesize that Raman signals can be enhanced by the use of IR screens coated with a few layer of graphene and, specifically, by those screens at resonance with the vibration frequency of the molecule. We have made graphenated metal screens with biotinylated lipid bilayers and conjugated streptavidin. We want to study protein binding to the lipid bilayers - a building block of cell membranes. The Raman signals exhibited clear angular dependence upon rotation and tilting of the screens with respect to the incident optical beam. Infrared spectroscopy is a complementary bio-detection detection tool to Raman. The absorption of the biotinylated lipid bilayer has exhibited strong dependence on the screen periodicity pitch as well as on its orientation. In conclusion, we have demonstrated that Raman and IR signals of bio-species are enhanced when the bio-species are placed on graphenated IR screens.
9:00 PM - AA7.5
Surface Enhanced Fluorescence of Bio-species on Nano-perforated Substrate of Anodized Aluminum Oxide (AAO).
Ruiqiong Li 1 , Antonin Marek 2 , Alex Smirnov 2 , Haim Grebel 1 Show Abstract
1 Electric Imaging Center at NJIT and ECE, New Jersey Institute of Tech., Newark, New Jersey, United States, 2 Department of Chemistry, NCSU, Raleigh, North Carolina, United States
9:00 PM - AA7.6
Investigation of the Surface Enhanced Raman Scattering by Confocal Raman Imaging.
Fan-Ching Chien 1 , ChiungWen Kuo 1 , Peilin Chen 1 Show Abstract
1 Research Center for Applied Sciences, Academia Sinica, Taipei Taiwan
It has been shown that the silver film over nanosphere (AgFON) substrates can induce the localized surface plasmon (LSP) to enhance the local electromagnetic field at the interface between the metal and dielectric medium. Such types of substrates could provide reliable surface enhanced Raman scattering (SERS) signals for the target molecules. Therefore, they have been routinely used as the sensors for the detection of biomolecules. It is believed that the strong SERS signal from these substrates can be attributed to the rough silver surfaces. However, there is a lack of direct experimental evidence for such argument. Here we report the study of SERS images of the Rhodamine 6G (R6G) molecules on the AgFON substrates using a confocal Raman microscope. To our surprise, about 50% Raman signals were originated from the defects of the AgFON at R6G concentrations of 10^-4 to 10^-8 M. According to the Raman images and AFM topography measurements, the distribution of active area, which was defined as the area with SERS intensity larger than 10% of the maximum SERS intensity, matched the defects between each domain of close packed nanoparticles. In addition, the defects between each domain were distributed randomly and uniformly on the AgFON substrates, which also explained that such type of substrates could provide a stable and reliable SERS signal of target molecules in bio- or chemical molecules detection applications.
9:00 PM - AA7.7
Shape Tuning from Gold Nanorods.
Enrique Carbo-Argibay 1 , Benito Rodriguez-Gonzalez 1 , Jessica Pacifico 1 , Isabel Pastoriza-Santos 1 , Jorge Perez-Juste 1 , Luis Liz-Marzan 1 Show Abstract
1 Physical Chemistry - Colloid Chemistry Group, University of Vigo, Vigo Spain
9:00 PM - AA7.8
Fabrication and SERS Properties of Shape-controlled Metal Nanodots using Anodic Porous Alumina.
Toshiaki Kondo 2 , Kazuyuki Nishio 1 2 , Hideki Masuda 1 2 Show Abstract
2 , Kanagawa Academy of Science and Technology, Kawasaki Japan, 1 , Tokyo Metropolitan University, Hachioji Japan
The fabrication of functional devices based on the localized surface plasmon (LSP) in small metal particles has attracted increasing attention due to its applicability in various fields, such as chemical or biological sensing. In this report, we show surface-enhanced Raman scattering (SERS) on an ordered array of metal nanodots prepared from a highly ordered anodic porous alumina mask, and the effect of the shape of nanodot on SERS intensity. The shape-controlled metal nanodot was obtained on various substrates by vacuum deposition through anodic porous alumina mask [1-3]. The shape of dot was controlled by changing deposition time and the geometry of porous alumina mask, for example, the period and shape of nanohole. Dependence of SERS intensity on the geometrical structures of dots was examined. SERS signals of pyridine molecules adsorbed on nanodots were detected. The intensities of the signals were dependent on the shape of nanodots. The geometrical structures of dots can be tuned to optimize the enhancement of SERS intensity. The obtained SERS substrates will be used for the Raman spectra measurement with high sensitivity. H. Masuda, and M. Satoh, Jpn. J. Appl. Phys., 35 (1996) L126 H. Masuda, H. Asoh, M. Watanabe, K. Nishio, M. Nakao, T. Tamamura, Adv. Mater., 13 (2001) 189 T. Kondo, F. Matsumoto, K. Nishio, H. Masuda, Chem. Lett., 37 (2008) 466
Peter Kiesel Palo Alto Research Center
David Nolte Purdue University
Xudong (Sherman) Fan University of Missouri
George Hong Millipore Corporation
AA8: Label Free Sensors for Complex Fluid I
Wednesday AM, December 03, 2008
Gardner A/B (Sheraton)
9:30 AM - **AA8.1
Optical Platforms for Label-Free Biosensing.
Robert Lieberman 1 Show Abstract
1 , Intelligent Optical Systems, Inc., Torrance, California, United States
The unique characteristics of biological substances make them excellent targets for optical detection (in "biodetectors"); these same properties can also be used to create highly sensitive and specific sensors for other substances (in "biologically-augmented chemical detectors"). Biosensors of both types have been created using a wide variety of optical techniques. This paper discusses the practical realization of several optical biosensors that can be used to determine chemical parameters in a variety of challenging environments using the inherent optical characteristics of native "unlabelled" biomolecules. // The simplest optical biosensors are biodetectors based on direct measurement of the optical properties of a target molecule. The most familiar example is the pulse oximeter, a device that determines the amount of oxygen carried by the hemoglobin in blood by measuring the absorption of infrared and red LED light transmitted through tissue. Other examples of direct-measurment biodetectors include refractometers that use total internal reflecton to determine sugar content in grape juice, scattering sensors used to determine turbidity in food production, and fluorescence-based fiber optic biofilm detectors. The materials used in these optical platforms must possess durability and biocompatibility, as well as a range of very specific optical characteristics. // In biologically-based sensors, changes in the properties of biological materials are used to sense other substances, which may or may not be biological. The unique ability of certain classes of biomolecules to "recognize" other molecules with a very high degree of specificity is a primary advantage of this type of sensor. DNA oligomers (short single-stranded segments of nucleic acids) chemically bind to their "complementary" strands with a very high affinity. Perhaps even more important as materials for biologically-augmented sensors are antibodies. These proteins are formed by animal immune systems in response to "contamination" by foreign substances -- whether other proteins associated with infectious cells and viruses, or toxic chemicals such as pesticides. Although fluorescent, absorbance-based, and even "mass-loading" labels have been used in biosensors, in many cases changes in the fundamental optical properties of the biomaterials themselves are quite sufficient to enable detection of thebinding of antibodies to their target antigens, or hyhbridization of "split" DNA to its target fragment. // Numerous platforms, ranging from fiber optic surface plasmon resonance probes to near-field optical scanners have been employed to detect biological recognition events. Biosensors that detect target-induced changes in the properties of entire living cells using diffactive optics, a panoply of refractometric techniques for biomolecular recognition, and many other optical biosensors, are now beginning to appear in laboratories and as commercially-available devices.
10:00 AM - **AA8.2
Amplifying Polymers for Ultrasensitive Sensors.
Timothy Swager 1 Show Abstract
1 Chemistry, MIT, Cambridge, Massachusetts, United States
10:30 AM - AA8.3
A Robust Chemometric Model for Determining the Chemical Composition of Human Coronary Artery with Raman Spectroscopy.
Jonathan Nazemi 1 , James Brennan 1 Show Abstract
1 Research and Development, Prescient Medical, Inc., Doylestown, Pennsylvania, United States
Background: The detection of vulnerable atherosclerotic plaques may be aided by classifying and quantifying the amounts of lipids within arterial wall, such as cholesterol and cholesterol esters. Previous researchers noted differing proportions of cholesterol and cholesterol esters between lipid pools and necrotic cores in atherosclerotic plaques. Raman spectroscopy is a rapid nondestructive technique which is capable of assaying these chemicals in human artery tissues and characterizing plaques in vivo. We have conducted a study to find the optimal chemometric model which correlates Raman spectra to the concentrations of cholesterol, cholesterol esters, triglycerides, and protein in human coronary tissue. Three standard chemometric methods – classical least squares (CLS), principal components analysis (PCA), and partial least squares (PLS) – are examined for their ability to produce minimum prediction error as a function of signal-to-noise ratio (SNR), important when utilizing the algorithms in a clinical environment. Methods: Tissue samples are prepared by submerging human coronary artery in liquid nitrogen and homogenizing it in a tissue pulverizer. Samples typically weigh ~80-100 mg. Raman spectra are taken from hundreds of locations throughout a sample volume by illuminating the tissue with ~75 mW of 671 nm light via a 100-um-core optical fiber. The resulting scattered light is collected by the same optical fiber and routed to a Raman spectroscopy system (River Diagnostics HPRM2500). Each mince is then submitted for standard chemical assays to provide relative concentrations of cholesterol, cholesterol esters, triglycerides, and protein. Three different chemometric models are developed utilizing either CLS, PCA, or PLS to correlate spectral measurements to chemical concentrations. Each resulting model is then used to predict the concentrations as Gaussian noise is added to each spectrum. Results: The model developed with PCA exhibited the smallest increase in prediction error with decreasing SNR, proving capable of predicting the concentrations of lipids and protein with a mean accuracy of ~98%. The PLS model was the next most robust model, followed by the CLS model, presumably due to the lack of orthogonality of the basis spectra. Conclusion: A robust chemometric model has been developed with PCA that can calculate concentrations from Raman spectra of cholesterol, cholesterol esters, triglycerides, and proteins in human coronary artery with a mean accuracy of ~98%. Cholesterol and cholesteryl esters can be determined with ≤2 % prediction error.
10:45 AM - AA8.4
Fabrication and Characterization of 2-D Plasmonic Crystals for Label-Free Immunodetection.
Andrea Valsesia 1 , Franco Marabelli 2 , Pascal Colpo 1 , Francois Rossi 1 Show Abstract
1 , European Commission JRC, Ispra Italy, 2 Physics "A. Volta", University of Pavia, Pavia Italy
Nowadays label-free biosensors based on optical detection are widely studied in view of their potential use in diagnostics, drug discovery and environmental monitoring. In particular methods exploiting the Surface Plasmon Polaritons (SPP) of uniform noble metallic films such as gold or silver have been widely studied leading to successful commercialization. Moreover, the development of advanced surface nanostructuring techniques has allowed the fabrication of biosensing surfaces based on the Localized-Surface Plasmon Resonance (L-SPR) effect, e.g. the use of Gold or Silver nanoparticles as local resonators to detect with high sensitivity the presence of immobilized biomolecules. Other advantages also from the technological point of view can be obtained by nanostructuring metallic thin films, because it allows the coupling of the light with SPP modes without the use of expensive quartz prisms. In this paper we propose a new method for the fabrication of highly sensitive biodetectors based on the production of functionalized nanoscale Plasmonic Crystal structure. The functionalized Plasmonic Crystal structure is a nanostructured surface constituted by bioadhesive polymeric nanopillars immersed in gold matrix. The fabrication method is based on the combination of cold-plasma processes and colloidal lithography techniques. The 2D-PlC was optically characterized by Angle Resolved – Micro Reflectometry in the spectral range between 400 nm and 1200 nm, inside a continuous flow liquid cell. The surface showed the typical optical response of a Plasmonic Crystal with an angle-dependent reflectivity spectrum characterized by both localized and delocalized Surface Plasmon Resonances. The spectral position of both the localized and the delocalized plasmonic resonances depends on the refractive index of the material interfacing the PlC surface. By monitoring the time-resolved changes in the spectral position of the peaks it is possible to measure the protein adsorption on the surface of the sensor with a sub-protein monolayer resolution.
11:15 AM - **AA8.5
Suspended Microchannel Resonators for Label-free Biomolecular Detection.
Scott Manalis 1 Show Abstract
1 , MIT, Cambridge, Massachusetts, United States
11:45 AM - **AA8.6
A Microfluidic Approach for Label-free Identification of Single Cells Based on Native Fluorescence.
Markus Beck 1 , Michael Bassler 1 , Peter Kiesel 1 , Noble Johnson 1 Show Abstract
1 , Palo Alto Research Center, Palo Alto, California, United States
The detection and characterization of single cells without the need for sample preparation is highly desirable. One of the approaches we pursue is on-the-flow detection of native fluorescence excited with ultraviolet light. Since the fluorescence spectra of the few fluorescent constituents in a cell are similar and most of them are present in varying amounts in different cells, the distinction between cells requires highly accurate measurements. In a microfluidic quartz channel, we excite the cells with a 266 nm laser and record the fluorescence light as the cells traverse the channel. Collecting the light with a fused silica fiber, we can measure the fluorescence spectra of single Bacillus Thuringiensis, Escherichia coli, and yeast cells in a conventional spectrometer in order to identify the spectral regions which are most suitable for their discrimination. We find that a few intensity ratios (distinguishing features) are sufficient to identify the cells, provided that these ratios can be determined with a maximum error of about 10%-20%. The accuracy required for this analysis was achieved by averaging over many cell spectra. In order to allow for single cell discrimination we have used a more sensitive setup to measure the distinguishing feature directly by simultaneously collecting the fluorescence intensities in two spectral ranges. We are thus able to resolve small differences in the spectra and therefore to identify the different species. A special modulation technique using a predefined pattern in the detection path of the fluorescence light, resulting in a time-modulated signal, allows us to determine the light intensity originating from the cell of interest independent from other light sources, such as other cells, stray light, fluorescence from the channel material, and from other sources of noise. We can thus improve the signal-to-noise ratio significantly. In addition, this technique allows us to precisely determine the particle speed and position. Consequently, closely spaced particles can be distinguished and the fluorescence intensity can be determined accurately even with a strongly non-uniform velocity distribution in our channel. This allows us to determine the intensity ratio of two spectral regions of interest with a statistical error of less than 10% even though the signals are close to the noise level. This work was partially funded under ONR contract N00014-05-C-0430 monitored by Paul Armistead, Jeremy Walker and Susan Rose-Pehrsson
12:45 PM - AA8.8
A Polymer-Based Optical Biosensor for Continuous Glucose Monitoring.
Louis Nemzer 1 , Arthur Epstein 1 2 Show Abstract
1 Physics, The Ohio State University, Columbus, Ohio, United States, 2 Chemistry, The Ohio State University, Columbus, Ohio, United States
AA9: Surface Enhanced Ramen
Wednesday PM, December 03, 2008
Gardner A/B (Sheraton)
2:30 PM - **AA9.1
Molecular Plasmonics: Nanoscale Sensing and Spectroscopy.
Richard Van Duyne 1 Show Abstract
1 Chemistry, Northwestern University, Evanston, Illinois, United States
During the last few years, there has been an explosion of interest and activity in the field of plasmonics. The goal is to control and manipulate light on the nanometer length scale using the properties of the collective electronic excitations in noble metal films or nanoparticles, known colloquially as surface plasmons. An improved understanding of the interactions between adsorbed molecules and plasmonic nanostructures (i.e., molecular plasmonics) is having a significant impact on many applications, including localized surface plasmon resonance (LSPR) spectroscopy  for chemical and biological sensing, sub-wavelength optical microscopy, surface-enhanced Raman spectroscopy (SERS),  and nanolithography.Plasmonics is a materials driven subject. The unifying theme in this lecture will be the fabrication of size and shape-tunable, silver and gold nanoparticles using nanosphere lithography (NSL), electron beam lithography (EBL), and chemical synthetic methods. Size and shape tunability leads to an exquisite degree of control over the magnitude and spatial extent of the surface electromagnetic fields that surround optically excited nanoparticles. In turn, this has enabled fundamental new insights into the electromagnetic (EM) field enhancement mechanism underlying both LSPR and SER spectroscopy. This lecture will cover recent developments in three areas of plasmonics research: (1) localized surface plasmon resonance spectroscopy; (2) surface enhanced Raman spectroscopy; and (3) the development of biosensors  based on both LSPR and SER spectroscopy. “Localized Surface Plasmon Spectroscopy and Sensing,” K. A. Willets and R. P. Van Duyne, Ann. Rev. Phys. Chem., 58, 267-297 (2007) “Surface-Enhanced Raman Spectroscopy,” P. Stiles, J. Dieringer, N. C. Shah, and R. P. Van Duyne, Ann. Rev. Anal. Chem., 1, 601-626 (2008) “Biosensing with plasmonic nanosensors,” J. N. Anker, W. P. Hall, O. Lyandres, J. Zhao, N. C. Shah, and R. P. Van Duyne, Nature Materials, 7, 442-453 (2008)
3:00 PM - AA9.2
Design of a Biocompatible and Optically-Stable Solution-Phase Substrate for SERS Detection.
Maryuri Roca 1 , Prescott Mackie 2 , Amanda Haes 1 Show Abstract
1 Department of Chemistry, The University of Iowa, Iowa City, Iowa, United States, 2 Biomedical Engineering, The University of Iowa, Iowa City, Iowa, United States
Detection of important biological molecules using surface-enhanced Raman scattering (SERS) has become widely used because of the highly sensitive and label free approach offered by SERS as well as the low cytotoxic response from some SERS substrates. Gold nanoparticles are commonly used in SERS studies; however, the inherent instability of these metal nanostructures in solution adversely influences the reproducibility and quantitative nature of these measurements. Furthermore, the metal surface often denatures biomolecules upon their direct interaction. To combat this incompatibility and improve optical stability, gold nanoparticles have been encapsulated in silica shells. These Au@SiO2 nanostructures have been used extensively in cellular studies, but their SERS capabilities are generally limited to uses that include silica-entrapped SERS reporter molecules rather than direct SERS detection. This work focuses on combating these limitations via the fabrication of Au@SiO2 nanoparticles with porous silica membranes for the direct detection of target molecules in solution. Gold nanoparticles have been designed and coated with a variety of silica morphologies and subsequently interrogated using extinction spectroscopy and SERS. It will be revealed that these gold nanoparticles entrapped in silica membranes serve as optically stable substrates for the quantitative and direct detection of target molecules. These advances in nanomaterial fabrication are envisioned to impact both fundamental and applied studies in a variety of research areas including catalysis, separations, and spectroscopy.
3:15 PM - AA9.3
Nanoscale Materials for Surface Enhanced Raman Spectroscopy.
Nathan Mack 1 , Stephen Doorn 1 , Hsing-Lin Wang 1 , Sea-Ho Jeon 1 Show Abstract
1 Chemistry, Los Alamos National Laboratory, Los Alamos, New Mexico, United States
The wealth of molecular information provided by surface enhanced Raman spectroscopy (SERS) makes it ideally suited for advanced sensing and detection applications. Under proper conditions, SERS enhancements can be on the order of 10^15 and in many cases begin to approach sensitivity levels seen in more common fluorescence based techniques. Recent approaches to fabricating SERS active substrates include nanoparticle aggregates, lithographically defined particle arrays, as well as electrochemically roughened electrodes, among others. While the exact mechanism responsible for efficient SERS enhancement is convoluted between several factors (electromagnetic, chemical, etc.), a common trait among these systems is the need for a well defined plasmon response that is associated with their nanoscale metallic surface features. Achieving this level of control over the SERS surface is often a compromise between easily fabricated regular arrays that have marginal enhancements and randomly generated surfaces that have large enhancements but very little synthetic control. For example, aggregated metallic nanoparticles produce extremely large SERS enhancements. However, the reproducibility from aggregate to aggregate is often suspect and the dynamic nature of individual aggregate architectures has limited their applicability in biosensing applications. Our work involves expanding the field of effective SERS substrates through a variety of surface based self assembly and nanoparticle synthetic techniques. This talk will focus on our recent advances in polyaniline based silver substrates which can be used to generate a wide variety of nanostructured silver features that are shown to be highly SERS active. This conducting polymer is capable of reducing aqueous silver ion solutions over large areas and gives a highly reproducible homogeneous SERS signal. Using these nanostructured substrates as a template, we engineer higher order nanoparticle and nanoshell based assemblies to produce 3-D SERS substrates with enhanced and tunable capabilities afforded by the plasmon resonance of the adsorbed particles. These materials are demonstrated in model biosensing applications to have potential for next generation sensor capacities.
3:30 PM - AA9.4
Label-free Cancer Gene Detection Using Surface-enhanced Raman Spectroscopy on Gold Nanohole Arrays.
Qiuming Yu 1 2 , Brian Christin 1 2 , Paul Wallace 1 2 , Scott Braswell 1 2 , Xiaoxia Gao 1 2 Show Abstract
1 Center for Nanotechnology, University of Washington, Seattle, Washington, United States, 2 Department of Chemical Engineering, University of Washington, Seattle, Washington, United States
Surface-enhanced Raman spectroscopy (SERS) has immerged as a powerful analytical and sensing tool for use in biomedical diagnostics and genomics analysis. This is due to its nondestructive nature and structural fingerprint capability with very narrow and highly resolved bands. The ability to detect specific DNA sequences or individual DNA bases within a sequenced genome is a key to the application in monitoring gene expression and evaluation or diagnostics of specific disease states including infectious and hereditary disease. In this work we use gold nanohole arrays as SERS substrates, immobilize cancer gene on the substrates and then detect the SERS signals of cancer gene directly. To make SERS as a robust and label-free sensor with high sensitivity and specificity, the nanostructure of noble metal has to be precisely fabricated in order to tune the local surface plasmon resonance to maximize the SERS, and the surface chemistry to tether ssDNA on nanostructured noble metal surfaces has to be well controlled to ensure that all ssDNA chains stand up on the surface and there are no non-specific bindings. We used electron beam lithography to fabricate gold nanohole arrays with precisely controlled diameter and spacing. The optimal SERS signal with the enhancement factor of 10e5 – 10e6 was obtained on the gold nanohole arrays with the nanohole diameter of ~400 nm and the edge-to-edge distance of 50 – 100 nm. The 5’ thiol-modified breast cancer susceptibility gene BRCA1 mixed with 6-mercapto-1-hexanol (MCH) forms a mixed self-assembled monolayer on the gold nanohole array substrate which serves as a DNA microarray. The SERS signal of cancer gene on the nanostructured surface was detected. The hybridization of complementary and mismatched cancer gene was also detected by SERS. The detection sensitivity was investigated by varying the density of the cancer gene on nanostructured gold surfaces. Combined with microfluidics, we develop an optical biosensor based on SERS platform for rapid, label-free, and real-time detection with high sensitivity and specificity.
3:45 PM - AA9.5
Patterning Surfaces with Enhanced Electromagnetic Fields using Chemical Assembly.
Sarah Adams 1 , Ju Choi 1 , Tyson Friday 2 , Heidi Bednar 2 , Amanda Haes 2 , Regina Ragan 1 Show Abstract
1 Chemical Engineering and Materials Science, University of California, Irvine, Irvine, California, United States, 2 Chemistry, University of Iowa, Iowa City, Iowa, United States
Nanoscale metallic structures have been utilized in the development of field-enhanced chemical and biological detection devices and have the capacity to achieve single-molecule level detection limits resulting from surface enhanced Raman scattering (SERS) due to the strong near field coupling between closely spaced noble metal nanostructures. Detection of the surface binding of biomolecules with localized surface plasmon resonance (LSPR) sensors also benefits from the incorporation of metal nanoparticles on surfaces. These devices would benefit from the development of techniques to pattern ordered arrays of metal nanoparticle clusters with sub 10 nanometer interparticle spacing in a cluster. Results on our development of patterning ordered arrays of noble metal nanoparticles having controlled size and shape on a self-organized polymer template will be presented. Poly(methyl methacrylate) domains in a phase-separated polystyrene-b-poly(methyl methacrylate) diblock copolymer thin film were chemically modified for controlled placement of monodisperse Au nanoparticles. Chemically synthesized gold nanoparticles, measured at 20 nm diameter using dynamic light scattering (DLS) techniques and SEM, were attached to these surface amine regions using 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride linking chemistry and N-hydroxy sulfosuccinimide stabilizer with an organic ligand, thiotic acid, on the nanoparticle surface. Optimization of thiotic acid functionalized particles in aqueous solution was analyzed to increase the electrostatic stability from zeta potential measurements as well as to reduce the presence of aggregate formation as observed in solution with dynamic light scattering (DLS) spectroscopic analysis and on the attached surfaces with SEM analysis. Atomic force microscopy and scanning electron microscopy images demonstrate that Au nanoparticles are preferentially immobilized on poly(methyl methacrylate) domains in polystyrene-b-poly(methyl methacrylate) thin films using this method. Preliminary SERS spectroscopic analysis of a monolayer of pyridine on this surface measured a SERS enhancement factor of the order of 107. The fabrication method of Au nanoparticle array assembly described here can be generalized to fabricate a variety of materials, structure and patterns. Hexagonal arrays of PMMA blocks within a PS matrix were formed on a variety of substrates, including silicon, glass, and gold as observed by SEM. Alternatively, to produce linear arrays of PMMA regions, the diblock copolymer was deposited and annealed on a polyimide layer deposited on the substrates. Thus, linear or hexagonal arrays of metal nanoparticle clusters can be fabricated.
AA10: Label Free Sensors for Complex Fluid II
Wednesday PM, December 03, 2008
Gardner A/B (Sheraton)
4:15 PM - **AA10.1
Biological Separation and Sensing with Electrochemically Programmed Multilayers of Porous Silicon.
Michael Sailor 1 Show Abstract
1 Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, United States
The chemistry and electrochemistry of nanoporous silicon can be manipulated to allow the material to collect, concentrate, and detect biological compounds with high fidelity. The pore dimensions are controlled by the current used in the etch , allowing the construction of stratified “nanoreactors” in which enzyme compartmentalization , reagent delivery , protein separation , and reactant heating  can be performed. The same process allows the fabrication of optical nanostructures that can be used to report on the presence of chemical or biological compounds without the use of labels. In addition, the optical nanostructures can be harnessed to improve the fidelity of a bioassay. As an example, the ability of a double-layer structure to provide compensation for zero point drift will be described. In this approach, two separate layers are etched into a crystalline Si substrate, one on top of the other. The optical reflectivity spectrum from such structures provides an effective means to discriminate analyte from interferents. Shifts in the spectrum from both layers are measured simultaneously. The two stacks provide a differential response, and the effect of zero point drift can be effectively nulled by calculating the weighted difference between the two peak wavelengths. Examples of the use of such structures to detect enzymatic digestion products will be presented. V. Lehmann, R. Stengl and A. Luigart, Mater. Sci. Eng., B, 2000, B69-70, 11-22.J. C. Thomas, C. Pacholski and M. J. Sailor, Lab Chip, 2006, 6, 782 - 787.J. R. Dorvee, A. M. Derfus, S. N. Bhatia and M. J. Sailor, Nature Mater., 2004, 3, 896-899.C. Pacholski, M. Sartor, M. J. Sailor, F. Cunin and G. M. Miskelly, J. Am. Chem. Soc., 2005, 127, 11636-11645.J.-H. Park, A. M. Derfus, E. Segal, K. S. Vecchio, S. N. Bhatia and M. J. Sailor, J. Am. Chem. Soc., 2006, 128 7938-7946.
4:45 PM - **AA10.2
Plasmonic Biosensing At The Single-cell Level.
Molly Gregas 1 2 , Jonathan Scaffidi 1 2 , Hsin-Neng Wang 1 2 , Tuan Vo-Dinh 1 2 3 Show Abstract
1 Biomedical Engineering, Duke University, Durham, North Carolina, United States, 2 Fitzpatrick Institute for Photonics, Duke University, Durham, North Carolina, United States, 3 Department of Chemistry, Duke University, Durham, North Carolina, United States
Plasmonically-active nanoprobes based on surface-enhanced Raman spectroscopy (SERS) combine high sensitivity with chemical and biomolecular specificity, making them ideal for molecularly-specific analysis within the intracellular environment. Through proper choice of molecular targets, our SERS nanosensing platform will allow single-cell examination of biological processes such as fertilization, mitosis and meiosis, DNA replication/damage/mutation, cell development, maturation and division, and programmed cell death (apoptosis). Herein we present proof-of-concept results illustrating critical milestones on the path to applying our nanosensors for in vivo single-cell analysis, including (1) use of molecularly-specific, SERS-based nanosensors for in vitro biochemical sensing, (2) use of SERS-based nanosensors for in vitro optical pH determination, and (3) demonstration that certain cell lines can take up chemically-sensitive silver nanoparticles through common endocytosis pathways. Planned future work will allow us to extend these results from our sensing platform to in vivo biochemical analysis with clinically relevant cell lines and animal models.
5:15 PM - AA10.3
Silicides for Infrared Surface Plasmon Resonance Biosensors.
Robert Peale 1 2 , Justin Cleary 1 , David Shelton 2 , Glenn Boreman 2 , Richard Soref 3 , Walter Buchwald 3 Show Abstract
1 Physics, University of Central Florida, Orlando, Florida, United States, 2 Optics, University of Central Florida, Orlando, Florida, United States, 3 AFRL/RYHC, Air Force Research Lab, Hanscom AFB, Massachusetts, United States
Biomolecules on a conductor strongly affect its surface plasmon modes, providing for real-time label-free sensing and monitoring of biomolecules. Established sensors are based on wavelength and angle dependent resonances in attenuated total reflection (ATR) or grating devices using visible/near-infrared light. Mid-IR operation using silicon-based materials offers a number of potential advantages. Large changes for the refractive index are expected near the characteristic IR vibrational frequencies of biomolecules, giving potentially better specificity. Semiconductor quantum cascade lasers have become available as IR sources with a broad range of design-tunable wavelengths. Silicon is highly transparent in the IR, and silicon-based devices offer benefits of integrated manufacturing and miniaturization. The large index of silicon allows observation in the ATR configuration of larger index values up to ~3.4 than can be observed in the visible with glass prisms (n ~1.5). This paper considers conducting silicides as IR surface plasmon hosts as opposed to the usual noble metals. Silicides may be grown by standard processing procedures directly on the polished surfaces of Si prisms or wafers, and gratings in silicides may be formed lithographically. The lower carrier concentration and plasma frequency of silicides relative to metals pushes surface plasmon dispersion curve farther from the light line in the IR, which is advantageous for observing resonances in the ATR configuration. Surface plasmons on silicides offer tighter mode confinement to increase the sensitivity to near-surface biomolecules. The higher surface impedance of silicides relative to metals gives more efficient coupling by gratings of IR into surface plasmons. Generation of IR surface plasmons by electron beams is more efficient for the silicides than for metals. This paper experimentally determines the IR permittivity for a number of industrially relevant silicides, including Pt-, Pd-, Ni-, Co-, and Ti-silicides. IR surface plasmon properties including mode profiles, propagation lengths, ATR lineshapes, and grating coupling efficiencies are then calculated for these materials. Experimental surface plasmon resonance data at CO2 laser wavelengths are then presented for both ATR and grating configurations.
5:30 PM - AA10.4
Investigation of Self-Assembled Monolayer Ordering on Indium Tin Oxide Surfaces for Surface Plasmon Resonance Sensors.
Mark Losego 1 , Alina Efremenko 2 , Crissy Rhodes 2 , Josh Guske 2 , H. Spalding Craft 1 , Marta Cerruti 2 4 , Daniel Fischer 3 , Cherno Jaye 3 , Stefan Franzen 2 , Jon-Paul Maria 1 Show Abstract
1 Materials Science, North Carolina State University, Raleigh, North Carolina, United States, 2 Chemistry, North Carolina State University, Raleigh, North Carolina, United States, 4 , UC Berkeley, Berkeley, California, United States, 3 , Brookhaven National Laboratory, Brookhaven, New York, United States
Devices utilizing surface plasmon resonance (SPR) to sense chemical / biological species or probe molecular interactions at surfaces are well established. Most devices employ the interface between a thin metal film, such as gold or silver, and a dielectric substrate to generate the necessary surface plasmon wave. However, metal films are limited to specific surface chemistries and their opacity restricts multiplexing with complimentary spectroscopic techniques. To expand the capabilities of SPR systems, transparent conducting oxides are investigated as a possible alternative materials set. We have previously demonstrated that the SPR response of the conductive oxide, indium tin oxide (ITO), can be controlled through an understanding of its electronic transport properties. The current challenge involves functionalizing the ITO surface with a properly structured organic layer that will bind target analytes. Like conventional noble metal SPR sensors, our approach is to use a self-assembled monolayer (SAM) as the inorganic / organic interfacing species. Ordered monolayers are expected to provide higher receptor site density and availability, improving detection limits. However, unlike more traditional platforms, ordering of SAMs on oxide surfaces is not as well understood and the 150 nm thick ITO films necessary for SPR response have nanometer scale roughness. In this work, near edge x-ray absorption fine structure (NEXAFS) spectroscopy is used to probe SAM ordering on ITO surfaces. Alkyl molecules with thiol and phosphonate functional groups are investigated for their assembly on these surfaces. By varying the ITO deposition conditions, the surface roughness of films on silicon substrates can be varied from 7 nm RMS to 0.8 nm RMS and lateral grain dimensions from > 1 micron to < 50 nm. These surfaces act as a test-bed for probing the effects of surface structure on monolayer ordering. Variations in alkyl chain length from 6 carbons to 18 carbons are also considered, and tilt angles are computed from the NEXAFS spectra. Through these experiments it is concluded that the strong binding chemistry of phosphonates to ITO make them suitable for ordered binding to the relatively rough surfaces found for films deposited on glass substrates used in standard SPR setups. However, through advanced material preparation procedures that modify the ITO surface chemistry (increase Sn:In ratio), thiol chemistries are also demonstrated to be viable candidates.
5:45 PM - AA10.5
Combining Chemical and Physical Molecular Recognition Elements for Enhancing Surface Plasmon Resonance Based Biodetecion.
Joseph Sly 1 , Fatemeh Parayandeh 2 , Cecile Bonifacio 2 , Lilian Chang 2 , Pierre Duhamel 1 , Melanie McNeil 2 , C. Jefferson 1 , William Risk 1 , Andre Knoesen 3 , Robert Miller 1 Show Abstract
1 , IBM ARC, San Jose, California, United States, 2 Chemical and Materials Engineering, San Jose State University, San Jose, California, United States, 3 Department of Electrical and Computer Engineering, University of California, Davis, California, United States