Abstract
Microfluidic techniques have emerged as a promising tool in the field of biomedical and clinical applications, due to their unique properties that allow for single-cell detection and manipulation, rapid chemical reactions, high throughput, minimal sample volume requirements, and integration with other technologies. In recent years, microfluidic electrical-based techniques that screen and classify heterogeneous single cells based on their intrinsic properties have gained significant attention, owing to their label-free nature and favorable biocompatibility. Microfluidic electrical-based cytometry has been the subject of numerous studies and has found practical applications in point-of-care diagnostics, including cell status monitoring, complete blood cell count, and rapid antimicrobial susceptibility testing. Despite these advances, the current state of microfluidic electrical-based cytometry faces unresolved challenges, including inaccuracies in particle characterization due to an inhomogeneous electric field, a lack of non-destructive cell status screening methods, and limited integration with other functionalities in single microfluidic chips, such as sorting, mixing, and emulsion. This dissertation, firstly, is to introduce a novel methodology for monitoring cell viability and other physical properties using microfluidic electrical-based cytometry, and to integrate this technology with focused traveling surface acoustic wave for single-cell manipulation, with the aim of enriching viable human peripheral blood mononuclear cells after cryopreservation. Additionally, the dissertation explores the integration of droplet microfluidics and electrical-based screening techniques to develop a new platform with the capabilities of on-chip droplet emulsion, label-free characterization, and purification of single or paired cells and microbeads within the emulsion. Finally, the dissertation reports on a new electrode configuration that overcomes the challenge of inhomogeneous electric fields, with unique advantages of nanoscale accuracy, cost-effectiveness, and ease of microfabrication. These studies represent a significant step forward in understanding single-cell electrical characterization and offer insights for future research into the expanded applications of microfluidic electrical-based cytometry.