Optimization of Microfluidic, Point of Care, Flow-Through, Bead-Based Microarrays: Towards Affordable Healthcare
McDevitt, John T.
Doctor of Philosophy
Recently, there has been much interest on the development of affordable, portable diagnostic devices for the detection of a wide range of analytes. Advancements in microfluidics and miniaturization bring promise for their use at the point of care over traditional, and for the most part laboratory-confined approaches. The integration of porous beads with microfluidics has demonstrated potential as highly sensitive sensing elements with the capability to detect multiple biological and chemical agents simultaneously. When used in a flow through microarray platform known as the Programmable Bio-Nano-Chip (p-BNC), these beads have demonstrated opportunities for detection of low volumes of sample under short analysis times. However, limitations in traditional microfluidic materials such as silicon and inefficient fractional capture of analytes by porous beads hinder the translation of the p-BNC into broad global and clinical adoption where tests are single use with short analysis times to detect low concentrations of sample. This dissertation aims to optimize the p-BNC through engineering design choices to enhance the performance and reduce the costs associated with the p-BNC. The development of a computational tool to model the porous bead-based system is described herein and used to lead in the design optimization of the system. This tool provides insights into the transport and capture of analytes within the bead array with capture performance as a function of flow rate, porosity, capture distances, molecular affinities, and binding densities. To transition away from a single use and expensive silicon-based microarray, a thermoplastics-based microarray, fabricated through the hot embossing of polyethylene from replicated molds from silicon, is developed and described. Further, to transition towards point of care conditions where sample volume is low and analysis times are short, the geometry of the bead microwell design is optimized to improve the fractional capture efficiency of analytes by the beads in flow through microcontainers. Finally, to improve the imprecision performance in bead-to-bead signal variation within the microarray, exploration of a split design and use of smaller beads reveal a decrease in imprecision.