Field-Free Isolation of Exosomes from Extracellular Vesicles by Microfluidic Viscoelastic Flows

TLDR

Exosomes, secreted by nearly all mammalian cells, are promising disease biomarkers, but their small 30–200 nm size makes isolation from complex extracellular vesicle mixtures difficult, especially in limited sample volumes. The study introduces a viscoelasticity‑based microfluidic system designed to directly separate exosomes from cell culture media or serum in a continuous, size‑dependent, label‑free manner. The device employs a small amount of biocompatible polymer to generate viscoelastic forces that drive size‑dependent separation of extracellular vesicles within the microchannel. Using this approach, the authors achieved over 90 % purity and more than 80 % recovery of exosomes, demonstrating a versatile platform for diverse biochemical applications.

Abstract

Exosomes, molecular cargos secreted by almost all mammalian cells, are considered as promising biomarkers to identify many diseases including cancers. However, the small size of exosomes (30-200 nm) poses serious challenges in their isolation from complex media containing a variety of extracellular vesicles (EVs) of different sizes, especially in small sample volumes. Here we present a viscoelasticity-based microfluidic system to directly separate exosomes from cell culture media or serum in a continuous, size-dependent, and label-free manner. Using a small amount of biocompatible polymer as the additive in the media to control the viscoelastic forces exerted on EVs, we are able to achieve a high separation purity (>90%) and recovery (>80%) of exosomes. The proposed technique may serve as a versatile platform to facilitate exosome analyses in diverse biochemical applications.