Combining 3D sidewall electrodes and contraction/expansion microstructures in microchip promotes isolation of cancer cells from red blood cells

Abstract

Cell sorting from heterogeneous organisms and tissues composed of multi-type cells is of great importance in biological and clinical applications. As promising cell sorting methods, dielectrophoresis (DEP) and hydrodynamics are attracting much attention in recent years. In this paper, we report a novel strategy by coupling DEP unit (3D sidewall electrodes) and hydrodynamic unit (microchannels with contraction/expansion structures) together in one microfluidic chip. Depending on the relative positions of 3D sidewall electrodes and contraction/expansion structure, three microchips (full-coupling, semi-coupling and non-coupling) are developed and their cell sorting performance are compared by isolating lung cancer cells (PC-9 cells) from red blood cells (RBCs). Both finite element simulation and practical cell sorting prove that high cell sorting efficiency (recovery of PC-9 cells: 90.21%, recovery of RBCs: 94.35%) can be achieved in full-coupling microchip, mainly owing to the synergistic effects between DEP sorting and hydrodynamic sorting. i.e., the positive DEP force generated by 3D sidewall electrodes can simultaneously act as an additional shear gradient lift force and thus trigger secondary flow even at low flow velocity. Live/dead cell staining, hemolysis ratio, fluorescence images and CCK-8 assay prove that RBCs and PC-9 cells show no significance difference in cell viability before and after cell sorting. The proposed coupling platform for cell sorting brings on a new pathway to construct integrated microfluidic chips for effective cell sorting and separation.