Development of printed-circuit-board based industry-compatible point-of-care biosensing and bioprocessing technology with applications

摘要

This thesis presents the development of a technology employing printed circuit board (PCB) technology to facilitate the performance and translation of point-of-care (POC) biosensing and bioprocessing devices toward practical products. Key features of the proposed technology are a universal, standardized platform and a set of techniques, featuring integrated functional units, three-dimensional (3D) configurations, convenient device-instrumentation interconnections, and industry-compatible precision manufacturing. The developed technology aims to incorporate and fabricate multiple functional units into a POC device with a compact configuration to perform bio/chemical sensing or processing that requires complex experimental conditions. In this thesis, PCB technology is employed to facilitate the development of three example biosensing and bioprocessing applications for proof of concept. First, the capability of using PCB substrates for complex assembly of functional components is demonstrated to facilitate the development of a chemistry-based enzyme assay. Proof-of-concept glucose-6-phosphate dehydrogenase (G6PD) deficiency assays are developed with integrated pH sensing units and temperature control units on boards. The assay is found to determine the G6PD level of a sample within 2 minutes. PCB technology is demonstrated to not only form an integrated platform but is also utilized in the fabrication of functional elements for biosensing and bioprocessing devices and systems. The second demonstrator is a molecule-based quantitative polymerase chain reaction (qPCR) device. A method is employed in this work to produce arrays of electrochemical biosensors and thermal cyclers using a three-metal PCB technology. The electrochemical performance and surface morphology of the biosensor microelectrodes are characterized and evaluated. The qPCR experiments are performed with 95% PCR efficiency and the detection limit of 59 deoxyribonucleic acid (DNA) copies. The third demonstrator is a cell-based on-board cooling rate controlled cryopreservation device. The possibility of meso-scale integration between the platform, sample storage and instrumentation is demonstrated in this work to facilitate the development of bioprocessing applications. On-board cooling-rate-controlled cryopreservation devices for use in low-temperature (-80°C) environments are developed with disposable, biocompatible polydimethylsiloxane (PDMS) storage chambers on top of localized feedback-controlled heaters on boards. These devices were able to maintain a stable cooling rate as low as 1°C per minute. Based on the work presented in this thesis, the future development plan and possible business models for the proposed technology are envisioned from academic and industrial perspectives to realize POC biosensing and bioprocessing applications toward commercialization.