Scalable Manufacturing of Microfluidics Devices for Emerging Needs in Precision Medicine
Creators: name: Stephens, Andrew
Publisher: name: My University
Year: 2023
Subjects: subject: Microfluidics
subject: Manufacturing
subject: Microfabrication
subject: Precision Medicine
subject: Immunoassay
subject: Biomedical Engineering
subject: FOS: Medical engineering
subject: Mechanical Engineering
subject: FOS: Mechanical engineering
subject: Engineering

description: Precision medicine is transforming healthcare from “one-size-fits-all” diagnosis and treatment, toward individualized therapies based on a person’s genomics, phenomics, and environment. It has been enabled largely by technological improvements in analytical tools used to collect these patient-specific data. As precision medicine expands into more fields of healthcare, demands increase for new technologies to support it. Microfluidics biosensing technologies offer significant potential for this purpose, but there is a lack of scalable manufacturing methods to translate these technologies into clinical use. To address this gap, this thesis has developed methods of converting microfluidics technologies made with conventional materials to materials compatible with high volume manufacturing technologies, specifically, wafer-level batch microfabrication. In the first part of the thesis, a fabrication process for a microfluidic cell sorter and incubator was developed using standard silicon-on-insulator (SOI) microfabrication methods. This work advanced the capabilities of cellular functional immunophenotyping by enabling sufficient device manufacturing throughput to examine a matrix of stimulation conditions that could be used to determine an optimal dose of an immunosuppressive drug in vitro. In the second part, a new method of micro-patterning proteins is developed for coating antibodies within hydrophilic-in-hydrophobic microwells. This bio-compatible fabrication method enabled the scale-down of the sensor area required for the “digital enzyme-linked immunosorbent assay (ELISA)”, capable of single-molecule detection. This enabled the construction of a highly sensitive and sample-sparing “digital protein microarray”, which enabled the longitudinal study of six serum cytokines related to glioma tumor progression in a cohort of mice at two time points without pooling samples or sacrificing animal models. In the third and final part, technical, practical, and economical bottlenecks for clinical translation of microfluidics biosensing technologies are identified through interviewing over 130 potential end users of the technologies developed in thesis. The findings of these interviews serve as case study for other microfluidics researchers developing clinical diagnostic technologies, which will inform critical technical decisions made early in the research process to maximize future societal impact. The technologies developed and findings presented have addressed the long-standing issues of manufacturing and clinical translation in over 30 years of research by the microfluidics community. The thesis will potentially accelerate the lab-to-application pipeline for microfluidics technologies urgently needed for the future of healthcare.