Reversible zwitterionic coordination enables rapid, high-yield, and high-purity isolation of extracellular vesicles from biofluids

Extracellular vesicles (EVs) hold great clinical value as promising diagnostic biomarkers and therapeutic agents. This field, however, is hindered by technical challenges in the isolation of EVs from biofluids for downstream purposes. We here report a rapid (<30 min) isolation method for EV extraction from diverse biofluids with yield and purity exceeding 90%. These high performances are ascribed to the reversible zwitterionic coordination between the phosphatidylcholine (PC) on EV membranes and the "PC-inverse" choline phosphate (CP) decorated on magnetic beads. By coupling this isolation method with proteomics, a set of differentially expressed proteins on the EVs were identified as potential colon cancer biomarkers. Last, we demonstrated that the EVs in various clinically relevant biofluids, such as blood serum, urine, and saliva, can also be isolated efficiently, outperforming the conventional approaches in terms of simplicity, speed, yield, and purity.