Microsystems technology for high-throughput single-cell sorting

Abstract The past 20 years have witnessed an explosive growth of microfluidic and microwell-based systems for biomedical research including high-throughput single-cell sorting and engineered microphysiological tissue chip systems. By and large, the development of polydimethylsiloxane (PDMS) soft molding has catalyzed this growth, and PDMS today remains the material of choice of the microsystems field. PDMS soft molding allows for the rapid and economical design of sophisticated microfluidic and microwell devices for a diversity of biomedical applications including the emerging frontier of testing the effects of micro/zero gravity (e.g., in space) on tissue homeostasis. The diversification of biomedical applications has, however, uncovered limitations of PDMS that are driving a need to explore new materials as well as the design of innovative architectures beyond shallow cuboid or cylindrical microwell structure for tissue chip and high-throughput cell-sorting application. Of particular interest are concave to spherical microwells that allow for spatial localization of cells but also provide for cell proliferation and concentration of cell-secreted factors. In this chapter, we discuss factors driving the development of high-throughput cell-screening technologies, the current state-of-the-art approaches, and the challenges that motivate emerging efforts to develop new material and device architectures.