Microfluidics to explore ultrafast cell deformations to deliver large cargo via convective transport

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Project Summary The delivery of molecules and particles to cells is important for increased scientific understanding of molecular processes and networks, detecting intracellular biomarkers in diagnostic targets, and genetic modification of therapeutic cells. The challenges associated with current delivery approaches include limits to the size of molecules that can be delivered (especially plasmid DNA), damage or modification to target cells, and a limit to the cell processing throughput. In studies to develop new methods that can be used to deliver molecules and particles more broadly to many cell types, a novel cellular behavior was discovered that occurs as cells are rapidly compressed at timescales faster than a millisecond. As a result of fast compressions upon cells, cells respond by a temporary change of volume, which results in a pressure driven flow across the cell membrane to restore cell volume, and as a byproduct carries extracellular reagents into a cell through a convective phenomenon. The goal of this study is to understand how to optimize devices exploiting a new biophysical regime of cell compression in which fast timescales (<1 millisecond), high strain (>30%) to impact cells. These physical impacts of cells are increasingly important to understand due to applications in lab on a chip, cell sorting, and cell engineering. Secondly, the microfluidic technology will be optimized and tested for microfluidic delivery of probes and labels, as well as transfection of large transgenes for a variety of important cell types. The understanding of cell mechanical responses in an unexplored region of time and magnitude could enable new approaches to label and reprogram the cell that will be efficient to a broad range of cell types and reagents.