MP45: A Powerful New High-Throughput Tool for Measuring the Deformability of Single Cells
Daniel R. Gossett, M.S.
Henry T.K. Tse, B.S.
University of California, Los Angeles
Los Angeles, CA U.S.A.
Serena Lee, Amander T. Clark, Dino Di Carlo
There is growing evidence that cell deformability (i.e. the ability to change shape under load) is a useful indicator of cytoskeletal variations and may provide a label-free biomarker for determining cell states or properties such as metastatic potential, cell cycle stage, degree of differentiation, and leukocyte activation. Clinically, a measure of metastatic potential could guide treatment decisions, or a measure of degree of differentiation could prevent transplantation of undifferentiated and tumorigenic stem cells in regenerative therapies. However, in order for deformability measurements to be clinically valuable, given the heterogeneity within a population of single cells, there exists a need for high-throughput automated assays of these mechanical properties. Here, we present a novel microfluidic device for the continuous deformation of cells in flow (~ 2,000 cells/sec, throughputs comparable to traditional flow cytometry and greater than 3 orders of magnitude over the current state-of-the-art methods). We have devised and fabricated a microfluidic system which uses previously reported inertial focusing techniques to precisely position cells in flow where they can be hydrodynamically stretched in an extensional flow. We have applied our system to the problem of screening cancer cells for their metastatic potential, measuring the deformability of normal (MCF10A), benign (MCF7), and malignant (MCF7 with enhanced motility) cell lines. Indeed, measureable differences in whole cell deformability exist in this model. We also explored a potential application in regenerative medicine and stem cell technologies as a tool for rapidly screening differentiation methodologies and identifying residual undifferentiated subpopulations in various embryonic stem cell differentiation protocols. Again, differences exist and preliminary results suggest that whole cell deformability may be an earlier biomarker for differentiation than currently used biochemical markers in some cell lines. Lastly, we have evaluated deformability of cells treated with cytoskeleton-acting drugs. Detectable differences from untreated, control cells suggest a potential application in rapid screening of cancer drug candidates or combinations for personalized medicine.
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