Microfluidic cell separation by deformability

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Fast, efficient isolation of specific phenotypes of cells from heterogeneous mixtures, such as blood and sea water, is important in many areas of biological and health sciences. Frequently, the desired cell types, such as Mesenchymal stem cells and circulating tumor cells, are extremely rare, with fractions ranging from 1:10^5 to 1:10^11 compared to the main population. Traditional cell sorting techniques use a range of physical parameters and chemical interactions to discriminate specific cell types. Physical techniques do not offer sufficient selectivity to isolate rare cells. Chemical techniques are undesirable because the processing steps required may prevent the recovery of cells for further analysis or transplantation into the body. Recent work in label-free cell separations using microfluidics structures has demonstrated size-based separation at low flow rates, but has a tendency to be clogged at higher flow rates. The fundamental limitation of these current mechanisms is their ability to process vast quantities of cells while remaining selective enough to isolate specific rare cell types. Our proposed research program will address these limitations by developing new mechanisms that separate cells by their mechanical deformability, which prior AFM studies have shown to vary significantly across different cell types. Using the approach to actively deform cells in flow, the proposed separation mechanisms are capable of processing vast quantities of cells at high flow rate without clogging. By leveraging microfabrication of structures at the size scale of individual cells, with instrumentation techniques to mechanically deform structures with nanometer precision, as well as, precise control of flow in using the tools of multilayer soft lithography, this research program aims to create a 'deformability spectrometer'.