Computational Simulations Of Circulating Tumor Cell Separation Using Microfluidic-based Approaches

As the rapid development of microfluidic chip technology,it has gained more attention in the field of biomedical research.This technology provides a new technological platform for studying cell motion and separation at the multicellular level.However,the flow characteristics and migration patterns of cells in the blood micro-environment are complex and have distinctive features in different types of blood vessels.Herein,we investigated the elongation deformation and shape relaxation dynamics of an isolated red blood cell(RBC)in the microchannel or microtube using dissipative particle dynamics technique.We examined the elastic response and relaxation behavior of the RBC under static tensile stretching and dynamic shear stress.On this basis,we simulated the flow and migration behavior of circulating tumor cell(CTC)in the deterministic lateral displacement(DLD)microfluidic devices.Based on the simulation analysis of the movement of RBC in the microchannel/microtube,we found that the confinement would slow down the cell relaxation process,especially under strong confinement conditions.We then simulated the motion of CTC and RBCs in the DLD-based microfluidic device and probed the effects of various parameters related to the fluid flow and DLD gap distance.We confirmed that the DLD-based microfluidic device had the capability of enhancing the efficient separation of CTC from RBCs,especially at large gap distance and moderate fluid shear stress.Overall,the simulation results reveal the mechanism of cell sorting at the microscale by studying the mechanical properties of RBC and the margination behavior of two types of cells in the DLD-based microfluidic device.These simulation findings could provide theoretical support for the design of new microfluidic chip to better exploit the flow properties of cells and efficient sorting and enrichment of CTCs.