Continuous medium exchange and cell isolation by size-selective passage through slanted micro-obstacles

The ability to isolate cells from contaminant particles such as cellular debris and simultaneously exchange the carrier medium of the cells is important for obtaining experimental integrity and optimal cell health. Although microfluidic manipulation techniques have demonstrated their ability to exchange the carrier medium of cells, they still require large device footprint (typically several cm(2)) that makes it difficult for them to be integrated into microfluidic systems. Here, we report a microfluidic device that overcomes the limitation by utilizing size-selective passage through slanted obstacles. A gap formed underneath the obstacles allows passage of small contaminant particles, while directing larger cells along the periphery of the obstacles. We demonstrated the utility of our device in a small device footprint of 0.05 mm(2) for efficient exchange of the carrier medium of mammalian cells, and achieved isolation of the cells from 1 mu m diameter contaminant particles in 4.4 ms with an enrichment factor of 834, an isolation purity of approximate to 70%, and a throughput of 465 cells min(-1).