(601j) A Microfluidics Platform for High-Throughput Contact-Dependent Cellular Interaction Studies

The contact-dependent cellular interaction is involved in wide variety of cellular phenomena, such as immunological synapse formation during antigen-recognition by T cell on an antigen-presenting cell. The exact mechanism of this event is not clear and is under intense research effort. However, most current experimental methods rely on random pairing between two interacting cell types, which severely limits the throughput of a given experiment. Thus an alternative experimental method with more deterministic mechanism and easy operation is needed.

Microfluidics has emerged as an important tool in biological research, especially in single cell analysis because of its micro-scale dimension. Despite several existing microfluidic platforms, the operability or efficiency is still not satisfactory. We have developed a novel microfluidic tool to facilitate studies of contact-dependent cellular interaction phenomena. By using pressure driven flow to achieve sequential hydrodynamic trapping of individual cells, we have demonstrated the arraying and pairing of two different cell types in a deterministic high-throughput manner. This approach has simple passive operation procedure, and does not rely on any electronic components. This tool only requires small sample size (2000 cells per cell type) and will enable fast observation (from initial contact) of contact-dependent cellular interactions in a high density manner (1 cell pair per 0.004 square millimeters). We found that the relative flow resistance along each flow path and the resulting flow ratio are the critical factors affecting cell loading and pairing efficiency. After optimizing of channel geometry, our technology can achieve initial antigen presenting cell loading efficiency of 90% and final pairing efficiency of 70%.