Cells are in a community and live in their microenvironment, which are highly sensitive to their microenvironment. The changing of cell microenvironment has direct or indirect effect on the cell behaviors. Observing the cell behaviors in a well-defined microenvironment is critical in many biological applications. However, most of the conventional approaches have some limitations, such as low throughput, complicated operation, and controlling microenvironment inaccurately. Therefore, developing new platforms to study the cell behaviors under different microenvironment plays a vital role in many areas, especially in cancer immune-therapy, gaining stem-cell-derived cells, and cell signaling. Here, my thesis focused on developing microfluidic platforms for controlling cell microenvironment...[ Read more ]

Cells are in a community and live in their microenvironment, which are highly sensitive to their microenvironment. The changing of cell microenvironment has direct or indirect effect on the cell behaviors. Observing the cell behaviors in a well-defined microenvironment is critical in many biological applications. However, most of the conventional approaches have some limitations, such as low throughput, complicated operation, and controlling microenvironment inaccurately. Therefore, developing new platforms to study the cell behaviors under different microenvironment plays a vital role in many areas, especially in cancer immune-therapy, gaining stem-cell-derived cells, and cell signaling. Here, my thesis focused on developing microfluidic platforms for controlling cell microenvironment and observing the cell behaviors.

A robust and straightforward microfluidic platform for cell-pairing and studying cell interactions at the single-cell level was first developed. It requires only two operational steps-capturing individual cells with hydrodynamic traps and subsequently relocating the capture cells by centrifugation. I paired individual dHL-60 cells and HeLa cells (HeLa-IL8, HeLa-IL10, and wild type HeLa cells). I found that these three HeLa cell lines give very different influences on the migration of dHL-60 cells. Then, a multilayer PMMA-based, reusable microfluidic platform to directly facilitate DOE in the differentiation of stem cells was developed. The chip consists of an inlet layer and multiple disperse layers. Different solutions are injected simultaneously to the chip through the inlet layer. Subsequently, the channels in the disperse layers split and recombine the flow streams to generate solution combinations based on hard-wired DOE designs. I used the chip to identify critical factors for cell differentiation to definitive endoderm. In addition, the DOE chip was also applied to combinational drug screening on tumor spheroids. I found that D-glucose can inhibit the effect of cisplatin on tumor spheroids, and tumor spheroids caused severe autophagy than 2D monoculture cells.