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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.

A spectrally integrated response method is proposed for analyzing transmission data from nanohole array sensors. This method increases the sensitivity by reducing noise and taking more information from the spectrum for bulk and surface sensing. Results from both real experiments and idealized simulations are presented. Comparison with two other methods- peak transmission wavelength shift and a normalized difference integrated response method are shown. This method shows improved sensing performance which can be exploited in future. Further improvement in sensing using nanohole arrays is explored by improving the instrumentation of the sensor system. Design parameters of the nanohole arrays for transmission at two different operating wavelengths were examined by using finite difference time domain simulations. Focused ion beam milling was used to fabricate chosen arrays. A microfluidic chip with the embedded nanohole array sensor was used to introduce different solutions for bulk chemical sensing. Intensity measurements were taken with a high speed CMOS camera. Sensing results using this system with possible improvements shows promise for future sensing applications. / Graduate

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.