Submicron Particle Focusing and Exosome Sorting by Wavy Microchannel Structures within Viscoelastic Fluids.

Exosomes, submicron membrane vesicles (30-200 nm) secreted by almost all cells, containing significant information such as proteins, microRNAs and DNAs, are closely associated with disease diagnostic and prognostic tests for liquid biopsy in clinical practice. However, their inherently small sizes lead to great challenges for isolating them from complex body fluids with high-throughput and high-purity. In this work, a reverse wavy channel structure using viscoelastic fluids with the addition of biocompatible polymer was presented for elasto-inertial focusing and sorting of submicron particles and exosomes. The microfluidic periodically reversed Dean secondary flow generated by repeated wavy channel structures could facilitate particle focusing compared with traditional straight channels. Four differently sized fluorescent submicron spheres (1 μm, 500 nm, 300 and 100 nm) were used to study the focusing behavior under various conditions. We have achieved simple, high-throughput, and label-free sorting of exosomes with purity higher than 92% and recovery higher than 81%. This developed elasto-inertial exosome sorting technique may provide a promising platform in various exosome-related biological research and pharmaceutical applications.