Multifunctional Detection of Extracellular Vesicles with Surface Plasmon Resonance Microscopy.

Extracellular vesicles (EVs), including exosomes, are promising circulating biomarkers for disease diagnosis. Conventional EVs analysis requires multiple instrumentations to obtain their phenotypic features, which limits its wide applications. Here, we present a plasmonic biosensor technology for multifunctional analysis of EVs. The system is based on a functionalized surface plasmon resonance (SPR) biosensor and an advanced plasmonic microscopy to capture and image EVs at single-particle level. SPR images are processed with a home-developed deep learning algorithm to identify EVs and quantify image intensity automatically. By combining immunosensing and single particle analysis, this approach enables both physical and chemical characterization of EVs. As a proof-of-concept, we applied it to analyze EVs secreted from human lung cancer A549 cell lines. Results show the capabilities in the detection of size, concentration and affinity constant. Due to the single particle imaging and multifunctional analysis capability, we anticipate that this technology will find use in clinical and scientific applications.