Large-scale engineered metallic nanstructures for high-throughput surface plasmon resonance biosensing and surface-enhanced Raman spectroscopy

Abstract

Precise measurements of binding kinetics and affinity of receptor-ligand interactions play an important role in pharmaceutical development as well as basic biology. Since a new drug discovery requires tremendous amount of time and cost, the demand for a high-throughput screening as well as precise kinetics measurement has increased dramatically. Although the commercially available BIAcoreTM system has been the gold standard for label-free and real-time biosensing, it is not capable of high-throughput kinetic measurements that are required for large-scale proteomics studies. To address the critical challenges, high-throughput SPR imaging instruments based on plasmonic nanohole arrays is demonstrated in this dissertation. The key advantage of nanohole-based SPR setup is that plasmons can be excited at normal incidence, which enables simple optical alignment and high-resolution imaging. Using template stripping technology, massively parallel and highly homogenous nanohole arrays, which is the prerequisite to perform high-throughput SPR imaging, are obtained over a large area (~cm2). Linewidths of extraordinary transmission (EOT) peaks are optimized by reducing the damping losses of surface plasmon polaritons (SPPs), leading to the improved detection limits of the sensor. By combining the highly parallel microfluidics with periodic nanohole arrays, our SPR imaging spectrometer system enables high-throughput, label-free, real-time SPR biosensing, and its full-spectral imaging capability increases the dynamic range of detection. Additionally, molecular identification via surface-enhanced Raman spectroscopy (SERS) is also presented in the second portion of the dissertation. Two approaches include planar-type nanohole structures aimed for highly reproducible SERS substrates with low-cost and dynamic nanogaps pearlchains via dielectrophoresis (DEP) for the rapid and ultrasensitive molecular detection and identification.