Studies of microfluidic devices for cell separation and analysis

Microfluidics has been proven to be an important platform for biological and chemical research. This dissertation focuses on affinity cell separation and cell culture in microfluidic devices. Three detailed studies are presented. First, surface ligand patterning is of vital importance for affinity separations. The ability to coat different ligands in separation devices can facilitate multi parameter cell sorting. A multi-region chip was developed with multiple separation zones in a single separation channel. Pneumatic control channels were used to define multiple antibody zones that could be used to compare several ligands for selective cell capture. Four different antibody regions were established in one channel to a cell line for sequential cell capture from a mixture. Many long-term assays require on-chip culturing of cells. The cell seeding step is critical for successful culture. Patterning multiple cell lines in one device will facilitate comparative studies of cell behavior among different cell lines and increase throughput. We proposed a convenient approach to pattern multiple cells in arrays of microfluidic chambers using one-step vacuum actuation. Eight individually addressable regions of culture chambers were integrated in one device, each only requiring one simple vacuum operation to seed cells. Four cell lines were cultured by low shear perfusion in the chip and their individual responses to apoptosis inducing compounds were compared. A 3D chip was recently developed in our group using multiple vertical-horizontal flow interfaces for negative enrichment target cells. Inspired by this design, elongated multiple vertical inlet units were created to deplete background cells for lower ratio target cell enrichment. The flow rate was first optimized for target cell purity. Then, a detailed study of effects of nonspecific bonding and sample mixture concentration was obtained.