Development of Localized Surface Plasmon Resonance-Based Point-of-Care System

This paper describes our point-of-care system development based on localized surface plasmon resonance (LSPR). Although LSPR has been a hot research area for a few decades, there are several bottlenecks which hampered its application for point-of-care (POC) medical diagnostics. The first is the detection sensitivity shortage when the direct LSPR wavelength shift is used for sensing, the second is the mass fabrication of durable metal nanostructures on the substrate, and the third is the microfluidic chip and the POC system which have to be combined with LSPR chips in a seamless but cost-effective way. To solve the above challenges, several novel technologies are initiated and successfully implemented in this work. To increase the sensitivity of the LSPR detection, we use plasmonic field to excite the fluorescence dyes conjugated to the analyte rather than directly detecting the LSPR wavelength shift upon analyte bonding. This method can enhance the biomarker detection sensitivity 10 to 100 times upon careful design of the metal nanostructures and the location of the fluorescence dyes in the bioassay. To mass fabricate the metal nanostructures, a 4aEuro(3) nickel mold is fabricated by electroplating and employed for UV nanoimprinting lithography. Our technology achieves high yield on wafer-level mass fabrication of the designed metal nanostructures. In terms of the surface modification of the bioassay, the orientation of the capturing antibody is controlled to enhance the sensitivity of biomarker detections, and an antifouling polymer is synthesized inside the gold nanoholes. To accomplish the cost-effective point-of-care system, a plastic multichamber microfluidic chip is fabricated, which contains the metal nanostructures, microfluidic channels, and trenches for controlling the sample flow. The microfluidic chip is inserted into a point-of-care system which consists of micropumps to control the microfluidic flow, a light source for fluorescence excitation, a camera system for fluorescence detection, and software to automate the POC system and to analyze the results. We believe this highly sensitive LSPR point-of-care system has ample applications on medical diagnostics.