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.
