SUMMARY

Cell biophysical properties are a new class of biomarkers that can be used to distinguish cells into subgroups. Microfluidic cell sorters are platforms that utilize these newly developed biomarkers to expand biomedical capabilities. Cell biophysical properties are attributed to cell structures which are important indicators for cell fate and functions. In particular, diseases such as cancer and malaria cause significant changes in cell biophysical properties. Therefore, cell biophysical properties have the potential to be used for disease diagnostics. Microfluidic channels are miniature systems designed to probe the cell structure transformation and exploit changes in biophysical properties to separate cells into subpopulations. In this combined theoretical and experimental investigation, we explore a new class of cell biomarkers and sort cells in microfluidic channels. The biomarkers are cell biophysical properties which include cell size, elasticity and viscosity. Atomic force microscopy and high-speed optical microscopy were used to directly characterize cells. We invented a microfluidic cell sorter for continuous, label-free cell separation utilizing variations in cell biophysical properties. The microfluidic channel is decorated by periodic diagonal ridges that compress the flowing cells in rapid succession. The compression in combination with secondary flows in the ridged microfluidic channel translates each cell perpendicular to the channel axis in relation to its biophysical properties. We found that the cell trajectories in the microfluidic cell sorter correlated to biophysical properties. We explain the physical principles of the cell sorting mechanisms and show that our microfluidic approach can be effectively used to separate a variety of cell types. Furthermore, we examine the effect of channel geometry, and flow rate under various experimental conditions to derive cell separation models that can be used to qualitatively predict cell sorting outcome. The major contribution is the invention and development of a novel microfluidic cell sorting platform that utilizes cell biophysical properties to sort and enrich cells. This innovative approach opens new ways for conducting rapid and low-cost cell analysis and disease diagnostics through biophysical markers.