Microfluidic Electro-Viscoelastic Separation of Submicron Particles and Extracellular Vesicles

Isolating submicron and nanoparticles in microfluidics is challenging due to weak separation forces and dominance of diffusion at the nanoscale. While the unfavorable scaling of the separation forces can be addressed by nanofluidic systems, the operation of such systems faces several limitations such as low throughput, high pressure requirements, and clogging. To overcome these issues, we present electro-viscoelastic particle separation─a method combining electrophoretic slip-induced lift with viscoelastic microfluidics to enhance lateral forces on nanoparticles. Using a standard microchannel (60 μm height, 20 μm width, and 3 cm length), we demonstrated fractionation of a mixture of submicron polystyrene particles with different sizes in a viscoelastic medium under an applied electric field. This system improved the purity of 50, 200, and 500 nm particles by 39%, 29%, and 50%, respectively. We further applied this technique to purify cancer cell–secreted extracellular vesicles (EVs) from background nanoscale contaminants such as soluble proteins, achieving a 22% increase in EV purity. Notably, our platform operates at blockage ratios as low as 0.002, which is a considerable improvement over its inertial and viscoelastic counterparts. These experimental findings highlight the potential of integrating electric fields with viscoelastic migration for effective nanoparticle separation. A comparison of our results with state-of-the-art theoretical models of electro-viscoelastic migration (EVM) suggests that the current understanding requires further advancement. Nevertheless, the enhanced electro-viscoelastic lift predicted by these models underscores the prospect of this technique for separation of bionanoparticles.