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Thesis (Ph. D.)--University of Washington, 2008. / Vita. Includes bibliographical references (leaves 125-136).

Thesis (Ph. D.) -- California Institute of Technology, 2010. / Title from home page (viewed 2/25/2010). Advisor and committee chair names found in the thesis' metadata record in the digital repository. Includes bibliographical references.

Label-free detection techniques have an important role in many applications, such as situations where few molecules -- rather than low molarity -- need to be detected, such as in single-cell screening. While surface plasmon resonance (SPR) scattering from metal nanoparticles has been shown to achieve significantly higher sensitivity in gene arrays, such an approach has not been demonstrated for protein arrays. SPR-based sensors could either use simple absorption measurement in a UV-Vis spectrometer or possibly surfaceenhanced Raman spectroscopy as the detection mechanism for molecules of interest. However, non-spherical particles are needed to achieve high sensitivity and field enhancement that is a requirement in both techniques, but these shapes are not easy toproduce reproducibly and preserve for extended periods of time. Here I present a carbonbased template-stripping method combined with nanosphere lithography (NSL). This fabrication allows to preserve the sharp features in atomically flat surfaces which are a composite of a non-spherical metal nano-particle (gold or silver) and a transparent embedding material such as glass. The stripping process is residue-free due to the introduction of a sacrificial carbon layer. The nanometer scale flat surface of our template stripping process is also precious for general protein absorption studies, because an inherent material contrast can resolve binding of layers on the 2 nm scale. These nanocomposite surfaces also allow us to tailor well-defined SPR extinction peaks with locations in the visible or infrared spectrum depending on the metal and the particle size and the degree of non-symmetry. As the particle thickness is reduced and the particle bisector length is increased, the peak position of the resonance shifts to the red. Not only the peak position shifts, but also the sensitivity to environmental changes increases. Therefore, the peak position of the resonance spectrum is dependent on the dielectric environmental changes of each particle, and the particle geometries. The resulting silver or gold nanoparticles in the surface of a glass slide are capable of detecting thiol surface modification, and biotin-streptavidin protein binding events. Since each gold or silver particle principally acts as an independent sensor, on the order of a few thousand molecules can be detected, and the sensor can be miniaturized without loss of sensitivity. UNSL-Au metal nanoparticle (MNP) sensors achieve the sensitivity of close to 300 nm/RIU which is higher than any other report of localized surface plasmon resonance (LSPR) sensors except gold nanocrescents. Finite-difference-time-domain (FDTD) and finite-element-method (FEM) numerical calculations display the influence of the sharp features on the resonance peak position. The maximum near-field intensity is dependent on the polarization direction, the sharpness of the feature, and the near-field confinement from the substrate. 3D FDTD simulation shows the local refractive index sensitivity of the gold truncated tetrahedron, which is in agreement with our experimental result. Both experimental and numerical calculations show that each particle can act as its own sensor.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (M. Eng.). / Written for the Dept. of Electrical and Computer Engineering. Title from title page of PDF (viewed 2008/01/14). Includes bibliographical references.

Thesis (M. S.)--Bioengineering, Georgia Institute of Technology, 2004. / William D. Hunt, Committee Chair ; Allen M. Orville, Committee Member ; Cheng Zhu, Committee Member ; Doug Armstrong, Committee Member ; Lawrence A. Bottomley, Committee Member. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 396-405).

Law Wing Cheung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references. / Abstracts in English and Chinese. / Abstract --- p.I / Acknowledgements --- p.V / List of Publications related to this project --- p.VI / Contents --- p.VII / Chapter Chapter 1 --- Introduction --- p.1-1 / Chapter Chapter 2 --- Literature Review / Chapter 2.1 --- Surface Plasmon Waves --- p.2-2 / Chapter 2.2 --- Excitation of Surface Plasmon --- p.2-4 / Chapter 2.2.1 --- Surface Plasmon Coupling Schemes --- p.2-6 / Chapter 2.3 --- Detection Techniques used in SPR sensors --- p.2-13 / Chapter 2.3.1 --- Angular Interrogation --- p.2-14 / Chapter 2.3.2 --- Wavelength Interrogation --- p.2-15 / Chapter 2.3.3 --- Intensity Interrogation --- p.2-16 / Chapter 2.3.4 --- Phase Interrogation --- p.2-16 / Chapter 2.3.5 --- Commercial SPR biosensors --- p.2-18 / Chapter 2.3.6 --- Comparison between Detection Techniques --- p.2-19 / Chapter 2.4 --- Applications of SPR biosensors --- p.2-21 / Chapter Chapter 3 --- Principle of Surface Plasmon Resonance Sensing Technology / Chapter 3.1 --- SPR Phenomenon --- p.3-1 / Chapter 3.2 --- Conditions for Surface Plasmon Resonance --- p.3-5 / Chapter 3.3 --- Wave-vectors --- p.3-7 / Chapter 3.4 --- Surface Plasmon Resonance described by Fresnel's Theory --- p.3-8 / Chapter 3.5 --- Concept of Surface Plasmon Resonance Biosensing --- p.3-10 / Chapter Chapter 4 --- Experiments / Chapter 4.1 --- Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on Mach-Zehnder configuration --- p.4-1 / Chapter 4.1.1 --- Materials required --- p.4-1 / Chapter 4.1.2 --- Experimental Setup --- p.4-2 / Chapter 4.1.3 --- Principle of Differential Phase Measurement --- p.4-3 / Chapter 4.1.4 --- Photodetector Circuitry --- p.4-6 / Chapter 4.1.5 --- Digital Signal Processing --- p.4-7 / Chapter 4.1.6 --- Polymer based Micro-fluidic System Integrated with SPR Biosensor --- p.4-9 / Chapter 4.2 --- Phase-sensitive Surface Plasmon Resonance Biosensor using the Photoelastic Modulation Technique --- p.4-12 / Chapter 4.2.1 --- Materials required --- p.4-12 / Chapter 4.2.2 --- Experimental Setup --- p.4-13 / Chapter 4.2.3 --- Principle of Photoelastic Modulation Technique and Signal Processing --- p.4-14 / Chapter 4.2.4 --- Operation Principle of Photoelastic Modulator --- p.4-17 / Chapter 4.3 --- Sample Preparations --- p.4-18 / Chapter 4.3.1 --- Glycerin-water Mixtures --- p.4-18 / Chapter 4.3.2 --- "PBS, BSA and BSA antibody" --- p.4-19 / Chapter 4.3.3 --- "RPMI, Trypsin, Cells and SDS" --- p.4-20 / Chapter Chapter5 --- Results amd Discussions / Chapter 5.1 --- Experimental setup I: Highly sensitive differential phase-sensitive surface plasmon resonance biosensor based on Mach-Zehnder configuration --- p.5-1 / Chapter 5.1.1 --- Measuring various glycerin-water concentration mixture with silver-gold sensing layer --- p.5-1 / Chapter 5.1.2 --- Comparison between the sensitivity of our setup and reported setup based on phase detection --- p.5-4 / Chapter 5.1.3 --- Discussion on 0.01° system resolution --- p.5-7 / Chapter 5.1.4 --- Experiment on monitoring BSA-BSA antibody binding reaction --- p.5-9 / Chapter 5.1.5 --- Matching oil and glass slide --- p.5-11 / Chapter 5.1.6 --- Experiments on monitoring BSA-BSA antibody binding reaction with integrated microfluidic system --- p.5-12 / Chapter 5.1.7 --- Experiment on observing cell adhesion properties on gold surface under the influence of trypsin --- p.5-14 / Chapter 5.1.8 --- Discussion on the non-specific binding between trypsin and gold surface --- p.5-16 / Chapter 5.1.9 --- Modifying the gold surface with BSA layer --- p.5-17 / Chapter 5.1.10 --- Experiment on observing cell adhesion properties on the gold surface under the influence Sodium Dodecyl Sulfate (SDS) --- p.5-18 / Chapter 5.2 --- Experimental setup II: Phase-sensitive surface plasmon resonance biosensor using the photoelastic modulation technique --- p.5-21 / Chapter 5.2.1 --- Measurement on difference glycerin-water concentration mixture --- p.5-21 / Chapter 5.2.2 --- Experiment on monitoring BSA-BSA antibody binding reaction --- p.5-23 / Chapter Chapter 6 --- Conclusions and Future Works / Chapter 6.1 --- Conclusions --- p.6-1 / Chapter 6.2 --- Future Works --- p.6-2 / References --- p.R-1 / Appendix / Chapter A. --- Phase Extraction Routine written by Matlab --- p.A-1 / Chapter B. --- Mathematical expressions for calculating the phase angle in the experiment of SPR biosensor using the Photoelastic Modulation Technique --- p.A-6 / Chapter C. --- Relationship between Concentration and Refractive Index of Glycerin-Water Mixture --- p.A-11 / Chapter D. --- Physical Properties of Bovine Serum Albumin --- p.A-12 / Chapter E. --- Simulation Curve written by Matlab --- p.A-13