Phase-Sensitive Surface Plasmon Resonance Imaging Based Sensor And Its Application

Surface Plasmon Resonance (SPR) sensing is an optical refractive index sensing technology with merits of high sensitivity, label-free and real-time detection. It has been widely applied in proteomics, genomics, drug kinetics analysis, environmental pollutants detection, food safety, etc. Conventional SPR sensors are based on amplitude detection and can be classified as intensity-interrogation, angle-interrogation and wavelength-interrogation. SPR sensors based on phase-interrogation emerge in late1990s. Since their resolution is2to3orders of magnitude lower than amplitude-sensitive ones (10-7-10-8RIU), phase-interrogation SPR sensors have received extensive research and shown great potential in practical applications.This thesis targets on the research of high-sensitivity and high-throughput SPR sensors based on phase detection and microfluidics. The body of this thesis consists of the sensitivity and noise simulation of phase-sensitive SPR sensing, phase extraction based on the prism phase modulator (PPM), fabrication of microfluidic chip and the setup and application of SPR phase imaging (SPR-PI) sensing system.1. Theory and simulation of phase-sensitive SPR sensing. This part will be presented in chapter1,2and3. The propagation equation of the Surface Plasmon wave will be derived based on Maxwell equations and the resonance condition for SPR will be discussed. In chapter3we will introduce the phase retrieval methods and the simulation results of the sensitivity and noise of phase-sensitive SPR sensing.2. Phase modulation and retrieval is the key technique in a phase-sensitive SPR sensor. We will introduce a novel prism phase modulator (PPM) in chapter4. Compared with conventional phase modulator, the PPM holds several advantages such as high modulation stability, high modulation depth and low-cost. The modulation result of the PPM and the phase retrieval methods will also be covered in chapter4.3. SPR microfluidic chip fabrication. High throughput and fast detection is important for biomolecular interaction analysis and drug screening. We have fabricated a SPR microfluidic chip with64sensing units,17flow channels and176gas actuated micro-valves. The highly integrated SPR microfluidic chip can remarkably increase the detection throughput and accelerate the detection speed. The fabrication methods and the performance of the microfluidic chip will be discussed in chapter5.4. Setup and application of the SPR-PI sensing. Combined with the PPM and the microfluidic chip, a SPR-PI sensing system is constructed in chapter6. Experimental result shows the detection resolution for liquid samples is7.61X10-7RIU. which is among the best resolutions for SPR-PI sensor in published literatures. The IgG-anti IgG interaction and Angiogenin-anti Angiogenin interaction are also demonstrated in the SPR-PI sensing system.