Ultrasensitive Protein Detection Technologies for Extracellular Vesicle Measurements

Extracellular vesicles (EVs) are nanoscopic, heterogenous, lipid-rich particles that carry a multitude of cargo bio-molecules including proteins, nucleic acids, and metabo-lites. Although historically EVs were regarded as cellular debris with no intrinsic value, growing understanding of EV biogenesis has led to the realization that EVs facilitate intercellular communication and are sources of liquid biomarkers. EVs can be isolated and analyzed from a wide variety of accessible biofluids for biomarker discovery and diagnostic applications. There is a diversity of EVs from different biological compartments (e.g., cells and tissues), and some of these EVs are present at extremely low concentrations. Consequently, a challenge in the field is to find appropriate markers that enable selective isolation of these rare EVs. Many conventional protein detection technologies have limited sensitivity to detect low abun-dance biomarkers in EVs, limiting their use in EV research. Advances in ultrasensitive detection technologies are needed to harness the potential of EVs for clinical appli-cation. This Perspective highlights current EV research focusing on ultrasensitive detection technologies, their limitations, and areas of potential growth in the future.

Automated summary

Extracellular vesicles (EVs) are small particles rich in lipids that carry proteins, nucleic acids, and metabolites. They play a crucial role in intercellular communication and can be isolated and analyzed from biofluids for biomarker discovery and diagnostics. However, the challenge lies in detecting and isolating rare EVs, which require ultrasensitive detection technologies.