Rapid Enrichment and Detection of Extracellular Vesicles Enabled by CuS-Enclosed Microgels

Extracellular vesicles (EVs) are cell-derived membranous vesicles that exist in nearly all biological fluids, including blood and urine; and carry a great number of cargo molecules such as protein, nucleic acids, and lipid. They may play important roles in cell-cell communication and modulation of pathological processes, which, however, are not yet well understood, calling for highly sensitive, specific, and rapid methods for EV detection and quantification in biological samples. Here, we report the CuS-enclosed microgels that not only help enrich EVs carrying specific protein markers from complex biomatrices, but also produce strong chemiluminescence (CL) to realize sensitive detection of the target EVs. A detection limit of 10⁴ EV particles/mL was achieved with these microgels by targeting EV proteins like CD63 and HER2, with a dynamic range up to 10⁸ particles/mL. Direct detection of EVs in human serum and cell culture medium without tedious sample preparation was demonstrated, consuming much less sample compared to ELISA and Western Blot. We envision that our method will be valuable for quick quantification of EVs in biological samples, benefiting disease monitoring and functional study.