Cancer is a leading cause of death and some types of cancer are hard to diagnose at early stages. An accurate method for subtype classification of cancer types is also critical for patients to receive effective treatments. Many cancer biomarkers (e.g., EGFR for lung cancers and CD19/CD20 for leukemia) have been found with potential of being used for cancer diagnosis and subtype cancer classification. A biosensing technique being able to detect biomarkers with a miniaturized system, based on extraordinary light transmission (EOT) through nanohole arrays on metal films, is promising for cancer diagnosis and subtype classifications. In this research, the detection of different biomarkers (EGFR, CD19 and CD20) was demonstrated using a surface plasmon resonance (SPR) setup with EOT. The concentration of EGFR from cell lysate solution was determined using the SPR setup and compared with a current analytical method (ELISA). The SPR setup gave a detection limit concentration of 0.77 g/mL for the EGFR. The EGFR concentration from the cell lysate was determined to be greater than 10 g/mL from SPR experiments; while a lower concentration of 0.604 g/mL was found from ELISA indicating some problems with the calibration curves obtained in the SPR experiments. A whole lung cancer cell capture experiment was also conducted using microscopy imaging and the SPR setup. A number of 11 2 cells/mm2 was captured from a pre-modified metal surface, which was confirmed by SPR. / Graduate / 0752 / 0541

Cancer is a leading cause of death and some types of cancer are hard to diagnose at early stages. An accurate method for subtype classification of cancer types is also critical for patients to receive effective treatments. Many cancer biomarkers (e.g., EGFR for lung cancers and CD19/CD20 for leukemia) have been found with potential of being used for cancer diagnosis and subtype cancer classification. A biosensing technique being able to detect biomarkers with a miniaturized system, based on extraordinary light transmission (EOT) through nanohole arrays on metal films, is promising for cancer diagnosis and subtype classifications. In this research, the detection of different biomarkers (EGFR, CD19 and CD20) was demonstrated using a surface plasmon resonance (SPR) setup with EOT. The concentration of EGFR from cell lysate solution was determined using the SPR setup and compared with a current analytical method (ELISA). The SPR setup gave a detection limit concentration of 0.77 µg/mL for the EGFR. The EGFR concentration from the cell lysate was determined to be greater than 10 µg/mL from SPR experiments; while a lower concentration of 0.604 µg/mL was found from ELISA indicating some problems with the calibration curves obtained in the SPR experiments. A whole lung cancer cell capture experiment was also conducted using microscopy imaging and the SPR setup. A number of 11 ± 2 cells/mm2 was captured from a pre-modified metal surface, which was confirmed by SPR. / Graduate / 0752 / 0541

This dissertation consists of two topics. One is a "Multi-pass Fiber Optic Surface Plasmon Resonance Sensor (SPR)" and the other is a "Nano-metallic Surface Plasmon Lens." Since both topics involved surface plasmon, the title of this dissertation is named "Surface plasmon coupled sensor and nanolens." For a multi-pass fiber optic SPR sensor, a fiber optic 4-pass SPR sensor coupled with a field-assist capability for detecting an extremely low concentration of charged particles is first demonstrated. The multipass feature increases the sensitivity by a factor equal to the number of passes. The field-assist feature forces charged particles/molecules to the SPR surface, increasing the sensitivity by an additional factor of about 100. Overall, the sensitivity exceeds the one-pass SPR device by a factor of about 400. A 10 pM concentration of 47 nm diameter polystyrene (PS) latex beads and 1 ?M concentration of salt dissolved in DI water were detected within a few seconds by the combined system. The equivalent index resolution for atomic size corresponding to ionized chlorine in salt is 10-8. This technique offers the potential for sensitive and fast detection of biomolecules in a solution. Secondly, a 44-pass fiber optic surface plasmon resonance (SPR) sensor coupled with a field-assist capability for measurement of refractive index change due to positive and negative ions is shown. The field-assist feature forces ions to the SPR surface, causing the SPR signal response to change which reflects a decrease or increase in refractive index depending on whether positive or negative ions are being attracted to the surface. This technique offers the potential for the sensitive detection of cations and anions in a solution. For a nano-metallic surface plasmon lens, we analyze the transmission of a normally incident plane wave through an Ag/dielectric layered concentric ring structure using finite difference time domain (FDTD) analysis. The dependency of the transmission efficiency on the refractive index in slit is studied. The numerical analysis indicates that the focusing beyond diffraction limit is found even at the extended focal length comparable to the distance of 7" from the exit plane using a circularly polarized coherent plane wave, ?=405 nm. Especially, compared to an Ag-only structure, the Ag/ LiNbO3 structure amplifies the transmission power by a factor of 6. Therefore, this Ag/dielectric layered lens has the potential for significantly higher resolution imaging and optical data storage.

Surface plasmon waves are TM polarized charge density waves that propagate at the interface of two media with real dielectric constants of opposite sign (i.e. liquid dielectric and certain metals). Surface plasmon resonance (SPR) sensors use these waves to detect refractive index changes adjacent to the metal layer. Refractive index changes arise from the binding of an analyte (e.g. a target molecule, protein, or bacterium) to the functionalized metal layer or from interfering effects such as changes in solution index. Standard, single channel SPR sensors cannot differentiate these two effects as their design allows only one mode to be coupled. This novel self-referencing technique employs two surface plasmon modes to simultaneously measure surface binding and solution refractive index. Dual surface plasmon modes are achieved by matching the refractive indices on either side of the metal film. The two modes generated - symmetric, long-range surface plasmon (LRSP) and anti-symmetric, short-range surface plasmon (SRSP) - have different field profiles and hence assist in differentiating solution refractive index changes from surface layer formation. Amorphous Teflon, with a refractive index close to water, is chosen as the buffer layer and gold is chosen as the metal layer. Magnesium fluoride, with a higher index than Teflon, is used as the buffer layer when using ethanol as the base solution. The sensor operation was optimized through simulations to yield higher sensitivity, lower reflectivity and resonances within the spectrometers range. Optimization results showed good performance over a wide range for Teflon, MgF2 and gold thicknesses which helped in the fabrication of the sensor. Demonstration of self-referencing operation was done through two different sets of experiments: (1) formation of an alkanethiol self-assembled monolayer on gold in the presence of ethanol and methanol solutions having different refractive indices and (2) streptavidin-biotin binding with solutions of different NaCl concentration and thus different refractive indices. In both these experiments, the resonance wavelengths were accurately predicted, reflectivity varied by 10-15% and sensitivity by 25% from that of the simulated values.

Surface-plasmon-resonance (SPR) sensors are widely used in biological, chemical, medical, and environmental sensing. This dissertation describes the design and development of dual-mode, self-referencing SPR sensors supporting two surface-plasmon modes (long- and short-range) which can differentiate surface binding interactions from bulk index changes at a single sensing location. Dual-mode SPR sensors have been optimized for surface limit of detection (LOD). In a wavelength interrogated optical setup, both surface plasmons are simultaneously excited at the same location and incident angle but at different wavelengths. To improve the sensor performance, a new approach to dual-mode SPR sensing is presented that offers improved differentiation between surface and bulk effects. By using an angular interrogation, both surface plasmons are simultaneously excited at the same location and wavelength but at different angles. Angular interrogation offers at least a factor of 3.6 improvement in surface and bulk cross-sensitivity compared to wavelength-interrogated dual-mode SPR sensors. Multi-mode SPR sensors supporting at least three surface-plasmon modes can differentiate a target surface effect from interfering surface effects and bulk index changes. This dissertation describes a tri-mode SPR sensor which supports three surface plasmon resonance modes at one single sensing position, where each mode is excited at a different wavelength. The tri-mode SPR sensor can successfully differentiate specific binding from the non-specific binding and bulk index changes.

A novel localized surface plasmon resonance (LSPR) sensor that differentiates between background refractive index changes and surface-binding of a target analyte (e.g. a target molecule, protein, or bacterium) is presented. Standard, single channel LSPR sensors cannot differentiate these two effects as their design allows only one mode to be coupled. This novel technique uses two surface plasmon modes to simultaneously measure surface binding and solution refractive index changes. This increases the sensitivity of the sensor. Different channels or modes can be created in sensors with the introduction of gold nanospheres or gold nanorods that act as receptor mechanisms. Once immobilization was achieved on gold nanospheres, the technique was optimized to achieve the same immobilization for gold nanorods to get the expected dual mode spectrum. Intricate fabrication methods are illustrated with using chemically terminated self assembled monolayers. Then the fabrication process advances from chemically silanized nanoparticles, on to specific and systematic patterns generated with the use of Electron Beam Lithography. Comparisons are made within the different methods used, and guidelines are set to create possible room for improvement. Some methods implemented failed, but there was a lot to learn from these unsuccessful outcomes. Finally, the applications of the dual mode sensor are introduced, and current venues where the sensors can be used in chemical and biological settings are discussed.