Microfluidic control of cell pairing and fusion

A device that traps cells in micrometer-sized capture cups efficiently achieves cell pairing and subsequent chemically or electrically induced fusion. The authors show that fused NIH 3T3 cells continue to be viable and morphologically normal off the chip, and they also show reprogramming of mouse embryonic fibroblasts after fusion with embryonic stem cells. Cell fusion has been used for many different purposes, including generation of hybridomas and reprogramming of somatic cells. The fusion step is the key event in initiation of these procedures. Standard fusion techniques, however, provide poor and random cell contact, leading to low yields. We present here a microfluidic device to trap and properly pair thousands of cells. Using this device, we paired different cell types, including fibroblasts, mouse embryonic stem cells and myeloma cells, achieving pairing efficiencies up to 70%. The device is compatible with both chemical and electrical fusion protocols. We observed that electrical fusion was more efficient than chemical fusion, with membrane reorganization efficiencies of up to 89%. We achieved greater than 50% properly paired and fused cells over the entire device, fivefold greater than with a commercial electrofusion chamber and observed reprogramming in hybrids between mouse embryonic stem cells and mouse embryonic fibroblasts.