Integrated Nanoplasmonic Optical Microfluidics for Label-free Bioassays

Current cellular assays are limited to multi-well based cell culture samples, and the existing cellular protein detection methods are restricted to labeling the targeting molecules with fluorescent dyes or other reporters. Microfluidic cell culture technology can provide precise and physiologically relevant microenvironment control to improve the quality of cell based assays. Nanoplasmonic optical probes enable the label-free detection of cellular protein with high temporal and spatial resolution. The goal of this dissertation is to develop and integrate real-time label-free nanoplasmonic detection with high-throughput microfluidic cell culture platforms. In this dissertation, several novel nanoplasmonic geometries, such as crescent-shaped nanoholes and nanocorals are developed to provide sensitive, robust and low-cost solutions for biomolecular detection. The sharp tips and large curvature features on the nanostructures are designed to maximize the sensitivity of both localized surface plasmon resonance (LSPR) peak shift and surface enhanced Raman spectroscopy (SERS) sensing applications. Two robust cell culture platforms - long-term single cell culture arrays and self-assembled tumor spheroid arrays - that facilitate monitoring arrayed cells with precise micro-environment control are also demonstrated. The integration of nanoplasmonic biosensors and microfluidic cell culture platforms are demonstrated on both chip-size and at the whole 4" wafer scale. Such integrated systems provide high resolution dynamic information on large array of precisely controlled cell populations. We expect this new tool will have significant impact on both fundamental cellular research and new drug evaluation