Exploiting micro-scale magnetic and acoustic phenomena in microfluidic devices for cell sorting applications.

摘要

The capability to sort specific biological targets from complex mixtures is critical for many biomedical applications, ranging from in vitro diagnostics to cell-based therapies. As these applications expand and demands on performance increase, a need has arisen for new technologies that are capable of high-purity, high-throughput separation. The use of microfluidics and micro-systems technology is a compelling approach to meet this demand. In this thesis, we present a series of microfluidic devices that exploit sub-mm-lengthscale phenomena in magnetics and acoustics for high-performance cell and particle separation.;First, we show an architecture to enable separation of multiple magnetic targets in a simultaneous manner. We demonstrate the capability to simultaneously sort multiple multiple bacterial cell types with > 90% purity and > 500-fold enrichment at a throughput of 109 cells/h.;We next report the use of ultrasonic standing waves to achieve cell cycle phase synchronization in mammalian cells in a high-throughput and reagent-free manner. We show that ultrasonic separation allows for gentle, scalable and label-free synchronization with high G1-phase synchrony (≈ 84%) and throughput (3 x 106 cells/h per microchannel).;Third, we discuss the integration of microfluidic acoutic and magnetic separation in a monolithic device for multi-parameter particle separation. Using our integrated device, we demonstrate high-purity separation of a multicomponent particle mixture at a throughput of up to 108 particles/h.;Subsequently, we describe a tunable acoustophoretic separation architecture capable of sorting cells and particles based on a range of sizes, analogous to a band-pass filter. We show that our device is capable of sorting an arbitrary particle size range between 3 and 10 mum in diameter with high efficiency (transfer fraction = 0.98 +/- 0.02) at a throughput of ≈ 10 8 particles/h per microchannel.;Finally, we discuss our ongoing efforts to develop a new device architecture for acoustic separation capable of greatly increased throughput. We demonstrate preliminary results showing separation of blood components at whole blood concentrations at a sample flow rate of about 1 L/h.