Abstract
Because of their structural and functional resemblance to real tissues, multicellular spheroids have been widely used as 3-D tissue models for basic cell biology studies and cell-based drug screenings. Spheroids have also been implicated as a powerful method to maintain or enhance cellular functions in primary cells and regulating the potency of stem cells. Recent advancement of microfluidic technology has provided scientists many capabilities including continuous dynamic perfusion and automatic fluidic control in performing cell culture. These functions are beneficial for growing cells in a long-term culture and their subsequent treatment and analysis. In this thesis, we first designed microfluidic systems to control cell differentiation at a specific site on a single spheroid. These strategies could controllably generate heterospheroids with a desired arrangement of multiple cell types, which meets the demand of a more complex MCS-based model for tissue surrogates for application in tissue engineering and cell-cell interaction studies. Furthermore, for the establishment of a well-manipulated process for spheroid productions and spheroid-based tests, we also generated a microfluidic device integrated with U-shaped PEG hydrogel microstructures that allow cell trapping, spheroid formation through self-assembly, and long-term culture of the spheroids. Heterospheroids generations and tests of anti-cancer drug on tumor spheroids have been accomplished and are potentially for automation through this microfluidic system. To summarize, we believe that applying the microfluidic techniques for establishment of desired 3D cell culture systems is beneficial for fundamental biological studies, drug-screening and other pharmaceutical application in the future.