Multifunctional Detection of Extracellular Vesicles with Surface Plasmon Resonance Microscopy

Abstract

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.

Emerging methods in biomarker identification for extracellular vesicle‐based liquid biopsy

“…Surface plasmon resonance (SPR) has been reported for the application of determining the EV number concentration (Im et al., 2017; Picciolini et al., 2018; Sina et al., 2019; Wang et al., 2019; Yang et al., 2020). The principles of the SPR technique rely on the excitation of oscillating free electrons occurring at the interface of a metal film and the medium (i.e., analytes) using a polarized light source.…”

Progress in Nanomaterials-Based Optical and Electrochemical Methods for the Assays of Exosomes

“…To date, a series of label-free SPR biosensors for exosome detection have been developed by modifying the sensor surface with antibodies specific to the membrane proteins on exosome. [136][137][138][139][140][141][142][143][144][145] To overcome the slow diffusion-limited mass transfer, magnetic nanoparticles can be utilized to pre-concentrate exosomes on the sensor surface under an external magnetic field gradient. 146 However, the poor sensitivity of the methods limits their further applications for analyzing trace targets in complex samples.…”

Matrix-assisted laser desorption ionization mass spectrometry profiling of plasma exosomes evaluates osteosarcoma metastasis

“…They are shed by almost all types of cells and found in various body fluids, such as plasma, urine, breast milk, saliva, etc . ( Chen et al., 2018 ; Costa-Silva et al., 2015 ; Di et al., 2019 ; Tieu et al., 2020 ; Yang et al., 2020 ). Exosomes play an important role in cellular communication, signal transduction and immune response and serve as potential biomarkers for various diseases ( Jansen et al., 2009 ; Saenz-Pipaon et al., 2020 ).…”