Cellular enrichment through microfluidic fractionation based on cell biomechanical properties.

The biomechanical properties of populations of diseased cells are shown to have differences from healthy populations of cells, yet the overlap of these biomechanical properties can limit their use in disease cell enrichment and detection. We report a new microfluidic cell enrichment technology that continuously fractionates cells through differences in biomechanical properties, resulting in highly pure cellular subpopulations. Cell fractionation is achieved in a microfluidic channel with an array of diagonal ridges that are designed to segregate biomechanically distinct cells to different locations in the channel. Due to the imposition of elastic and viscous forces during cellular compression, which are a function of cell biomechanical properties including size and viscoelasticity, larger, stiffer and less viscos cells migrate parallel to the diagonal ridges and exhibit positive lateral displacement. On the other hand, smaller, softer and more viscous cells migrate perpendicular to the diagonal ridges due to circulatory flow induced by the ridges and result in negative lateral displacement. Multiple outlets are then utilized to collect cells with finer gradation of differences in cell biomechanical properties. The result is that cell fractionation dramatically improves cell separation efficiency compared to binary outputs and enables the measurement of subtle biomechanical differences within a single cell type. As a proof-of-concept demonstration, we mix two different leukemia cell lines (K562 and HL60) and utilize cell fractionation to achieve over 45-fold enhancement of cell populations, with high purity cellular enrichment (90% to 99%) of each cell line. In addition, we demonstrate cell fractionation of a single cell type (K562 cells) into subpopulations and characterize the variations of biomechanical properties of the separated cells with atomic force microscopy. These results will be beneficial to obtaining label-free separation of cellular mixtures, or to better investigate the origins of biomechanical differences in a single cell type.