In this dissertation, we studied the biosensing properties of plasmonic nanoparticle in solution and on substrates. We optimized and modify the nanoparticles towards sensitive, multiplexed and portable biosensors and used them for biosensing applications.

In the first chapter, the basis of plasmonic biosensing was summarized including the mechanism, properties and affecting factors. We reviewed the work that have been done to optimized plasmonic nanoparticles towards sensitivity and signal amplification, advances in multiplex and microfluidic device and breakthroughs about novel portable plasmonic substrates. We summarized the advantages and disadvantages of the current work and introduce briefly about our effort to overcome these disadvantages.

In the second chapter, we reported an easy method for making chip, uniform and sensitive multiplexed and microfluidic device by combining photolithography and hole-mask colloidal lithography. The microfluidic device was determined to be ideal for biophysical kinetics measurements while the multiplexed device allowed fast and high throughput screening. These devices are potential for point-of-care diagnostics with relatively low cost.

In the third chapter, we optimized the surface chemistry of gold nanorod and nanostar to increase the ability for biofunctionalization and modification. By chemically treating the nanoparticle surface with NaBH4, we found it was easy to replace the harmful or tightly bound capping agent on nanoparticle surface and replace with other mild chemicals with functional groups. This method not only increased the flexibility of surface chemistry, but also greatly enhanced the sensitivity for biosensing.

The fourth chapter applied and modified the fabrication method on the flexible plastic substrate instead of conventional glass/silica wafer substrates. The active chemical property and thermoplasticity of plastic film allows deep etching and stretching on the substrate. Based on this, we fabricated honeycomb-shaped nanostructures by deep etching and elongated nanoparticles by stretching. These nanostructures show unique optical properties including enhanced SERS (surface enhanced Raman scattering). This method provides an easy way to fabricate asymmetric nanostructures on the surface and increase the portability of substrate. In the fifth chapter, we report applications of the plasmonic substrates made above for sexually transmitted disease (STD) detection and high throughput drug screening. For the STD detection, DNA strand is extracted from pathogen cell and attached to gold nanoparticle array surface for LSPR measurement without amplification. So far we are seeing 10000 cells limit of detection with an easy and fast procedure. For the drug screening, a 96 plasmonic spot plate is used to screen a drug for Human antigen R (HuR). This is realized by a LSPR method by finding the right drug that can block HuR and RNA interaction.