A Cheap Little Chip: Simplifying Cell Therapies

Abstract

Efficient intracellular delivery of target macromolecules remains a major obstacle in cell engineering, cell labeling, and other biomedical applications. Our lab has discovered the unique cell biophysical phenomenon of convective intracellular macromolecule delivery using mechanically induced, transient cell volume exchange. Ultrafast microfluidic cell compressions are used to cause brief, deformation-induced cell volume loss followed by volume recovery through uptake of surrounding fluid. Macromolecules suspended in the surrounding fluid enter the cell on convective fluid currents. We harness this cell volume exchange behavior for high-throughput, convective intracellular delivery of large macromolecules, including plasmids (>10 kb) and particles (>30 nm), while maintaining high cell viability (>95%). Successful experiments in transfection and intracellular labeling demonstrate potential to overcome the most prohibitive challenges in intracellular delivery for cell engineering.