Metallic Nanostructures and Plasmonic Devices for Surface Plasmon Resonance Biosensing

Abstract

High-throughput real-time sensing of molecular binding kinetics is important for drug discovery, basic biology, and the emerging field of proteomics. In particular, label-free <italic>surface plasmon resonance</italic> (SPR) sensing, which harnesses electromagnetic surface waves excited on metallic nanostructures, has been widely used in pharmaceutical development. Despite successful commercialization, the reflection-based configuration of traditional SPR instruments suffer from high cost, low sensing throughput, and incompatibility of studying molecules in cell membranes. In this dissertation, a new SPR biosensor based on plasmonic nanohole arrays made in metallic films is demonstrated. These biosensors are used for multiplexed sensing of molecular interactions in a quantitative manner. The nanohole-based SPR devices measure transmission of normally-incident light and the co-linear optical transmission setup offers simple optical setup and high-resolution imaging capability, leading to high-throughput multiplex kinetic assays for protein microarray applications. Additionally, the nanoholes can readily incorporate lipid membranes to study antibody binding to lipids and membrane-bound proteins. Newly developed nanofabrication methods enable production of large-area nanohole- and nanogap arrays in an inexpensive and high-throughput fashion. These methods may facilitate wide dissemination of nanohole SPR sensing as well as chemical sensing <italic>via surface-enhanced Raman spectroscopy</italic? (SERS) for biomedical applications.