Recent advances in miniaturization have brought a great deal of opportunities in life sciences and clinical research. Transforming conventional experiments into miniaturized platforms offers unprecedented possibilities with such benefits as less sample volume, faster analysis time, more precise control, automation, and massive parallelization. Amongst, the utilization of integrated microcapillaries to emulate conventional glass micropipettes and their crucial role in life sciences aims to revolutionize relevant techniques which are laborious, skill laden and hence extremely low throughput. In this thesis, a comprehensive study was undertaken with emphasis on process technologies for the integration of microcapillaries and their cell-based applications.

Novel process technologies have...[ Read more ]

Recent advances in miniaturization have brought a great deal of opportunities in life sciences and clinical research. Transforming conventional experiments into miniaturized platforms offers unprecedented possibilities with such benefits as less sample volume, faster analysis time, more precise control, automation, and massive parallelization. Amongst, the utilization of integrated microcapillaries to emulate conventional glass micropipettes and their crucial role in life sciences aims to revolutionize relevant techniques which are laborious, skill laden and hence extremely low throughput. In this thesis, a comprehensive study was undertaken with emphasis on process technologies for the integration of microcapillaries and their cell-based applications.

Novel process technologies have been introduced to obtain functional microcapillaries. First, the integration of glass microcapillaries and 3D silicon microelectrodes is demonstrated for active manipulation and positioning of individual cells at specific sites where microcapillaries establish exclusive access to the captured cells. Second, microcapillaries, since processing silicon is fairly well established, are demonstrated entirely in silicon by taking advantage of silicon surface migration, a technique that has been rarely explored in microfluidics. Third, leveraging rapid turnaround time of soft lithography, microcapillaries are introduced into transparent elastomer substrate, polydimethylsiloxane (PDMS). The utility of these platforms has been showcased on probing cells electrically and/or optically in whole-cell impedance spectroscopy and patch clamping as well as on flow-through electroporation of cells.

Precise manipulation and positioning of target cells on these platforms are typically realized through hydrodynamic and/or dielectrophoretic (DEP) forces. Alternative to conventional DEP approach where solid microelectrodes are utilized, a new DEP scheme, namely microcapillary-assisted dielectrophoresis (μC-DEP), is introduced, replacing solid microelectrodes with a liquid electrolyte so as to avoid shortcomings. In this scheme, microcapillaries serve as a “salt bridge” between liquid electrolyte and a stream of cells or particles kept at a lower conductivity to engage positive DEP forces for their effective trapping. More importantly, this platform also leads to an interesting observation of particle trapping in direct contrast with DEP theory, which can be attributed to the unique microenvironment whereby cells or particles exposed to both electric field gradient and conductivity gradient simultaneously. A plausible hypothesis is presented here based on a new type of force, the so-called concentration polarization (CP), and diffusiophoresis. This argument is further supported by comparing the velocity measured by high-speed video microscopy imaging on the particle trapping and that obtained from numerical solutions. Last, DEP experiments are performed on a semiconductor compound (AlGaN/GaN) as a potential substrate to integrate microcapillaries. An interesting discovery concerning the particle response to DEP under UV illumination is noted and further explained through UV-induced electron-hole pair generation and the subsequent charge redistribution in AlGaN/GaN heterostructure.