Label-free imaging and biomarker analysis of exosomes with plasmonic scattering microscopy

Exosome analysis is a promising tool for clinical and biological research applications. However, detection and biomarker quantification of exosomes is technically challenging because they are small and highly heterogeneous. Researchers at Arizona State University have developed an optical approach for imaging exosomes and quantifying their protein markers without labels using plasmonic scattering microscopy (PSM). PSM can provide improved spatial resolution and distortion free image compared to conventional surface plasmon resonance (SPR) microscopy, with signal-to-noise ratio similar to objective coupled surface plasmon resonance (SPR) microscopy, and millimeter-scale field of view as prism coupled SPR system, thus allowing exosome size distribution analysis with high throughput. In addition, PSM retains the high specificity and surface sensitivity of the SPR sensors, and thus allows selection of exosomes from extracellular vesicles with antibody modified sensor surfaces and in-situ analyzing binding kinetics between antibody and the surface protein biomarkers on the captured exosomes. Finally, the PSM can be easily constructed on a popular prism-coupled SPR system with commercially available components. Thus, it may provide an economical and powerful tool for clinical exosome analysis and exploration of fundamental issues such as exosome biomarker binding properties.


a, and b Simplified sketches of the optical setups for SPR microscopy (a) and PSM (b), and their images of one 93.7 nm polystyrene nanoparticle (PSNP). c, Integrated and differential PSM images monitoring the binding of 93.7 nm PSNP onto the gold surface. The dynamic process is shown in Movie S1. d, PSM image intensity histograms of the PSNP with different diameters, where the solid lines are lognormal fittings and the mean image intensities are marked. e, Mean PSM image intensity versus PSNP diameter. The z-distance dependence of surface plasmonic waves is considered (Note S1). Incident light intensity is 0.1 W/cm2 for SPR microscopy and 4 W/cm2 for PSM.

Zhang P, Jiang J, Zhou X, Kolay J, Wang R, Wan Z, Wang S. (2022) Label-free imaging and biomarker analysis of exosomes with plasmonic scattering microscopy. Chem Sci [Epub ahead of print]. [abstract]

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