Deformability based cell margination - A simple microfluidic design for malarial infected red blood cell filtration

摘要

In blood vessels with luminal diameter less than 300μm, red blood cells (RBCs) which are smaller in size and more deformable than leukocytes, tend to migrate to the axial centre of the vessel due to the Poiseuille nature of flow within these small capillaries, thus displacing the larger (and less deformable) leukocytes to the vessel wall; a phenomenon aptly termed as margination. In this work, this physiological event is mimicked in microfluidic systems for the biological separation of malarial infected RBCs (iRBCs) from whole blood. Change in cell stiffness is a characteristic of iRBCs which can act as an intrinsic biomarker for separation. Tests were conducted using early ring stage and late trophozoite/schizont stage iRBCs which vary significantly in their deformability. Filtration efficiency was quantified by analyzing the dispersion of these fluorescently labeled microbeads and iRBCs across the microchannel width at the outlet. Flow cytometry analysis was also conducted on the outlet samples to confirm filtration results. Our results indicate filtration efficiency of -75% for early ring stage iRBCs and >90% for late stage iRBCs. This is the first demonstration applying this unique biomimetic separation technique to iRBCs filtration for disease diagnostic application. The simple and passive operation of the system makes it ideal for on-site testing in resource poor settings and can be readily applied to other blood cell diseases such as sickle cell anemia and leukemia which are also characterized by change in cell stiffness.