Recent progress in surface-enhanced Raman spectroscopy-based biosensors for the detection of extracellular vesicles.

Extracellular vesicles (EVs) are a type of mediator that enables intercellular communication. Moreover, EVs carry critical molecular information from parental cells, making them ideal biomarkers for clinical screening and diagnosis. Currently, several sensing technologies have been established to sensitively detect EVs. Among them, surface-enhanced Raman spectroscopy (SERS) has become a powerful analytical tool with high sensitivity and low detection limits. In this review, we first cover the biological characteristics of EVs and the principle of SERS amplification. Then, we describe the recent progress in SERS technology applied to detect EVs, including direct label-free methods and indirect labeling strategies, in which substrate fabrication and nanoprobe assembly were emphasized. Furthermore, SERS technology could also be used to characterize or monitor the behavior of programmable EVs. Finally, we discuss the prospects and issues to be addressed for the development of SERS technology for EV analysis.