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Edited by Catherine J. Murphy, University of Illinois at Urbana–Champaign, Urbana, IL, and approved August 29, 2018 (received for review March 15, 2018)
Significance
Exosomes are tiny vesicles secreted by cells that play an important role in cell-to-cell communication. The RNA, DNA, and proteins in exosomes are reported to be critical biomarkers for precision diagnostics and therapeutics. Exosome analysis thus offers an approach to learn health conditions without tissue biopsy. Clinical application and fundamental study of exosomes require analytical tools capable of physical and biochemical characterization. The challenge in developing such tools lies in that conventional optical microscopy is not suitable for exosome analysis due to its limited sensitivity. In this paper, we report a plasmonic microscopy capable of imaging single exosomes and quantitative analysis of physical (size) and biochemical (interaction with antibody) information.
Abstract
Exosomes play an important role in numerous cellular processes. Fundamental study and practical use of exosomes are significantly constrained by the lack of analytical tools capable of physical and biochemical characterization. In this paper, we present an optical approach capable of imaging single exosomes in a label-free manner, using interferometric plasmonic microscopy. We demonstrate monitoring of the real-time adsorption of exosomes onto a chemically modified Au surface, calculating the image intensity, and determining the size distribution. The sizing capability enables us to quantitatively measure the membrane fusion activity between exosomes and liposomes. We also report the recording of the dynamic interaction between exosomes and antibodies at the single-exosome level, and the tracking of hit-stay-run behavior of exosomes on an antibody-coated surface. We anticipate that the proposed method will contribute to clinical exosome analysis and to the exploration of fundamental issues such as the exosome–antibody binding kinetics.
Footnotes
- ↵1To whom correspondence may be addressed. Email: dingxianting{at}sjtu.edu.cn or hui.yu{at}sjtu.edu.cn.
Author contributions: X.D. and H.Y. designed research; Y.Y., G.S., and H.Y. performed research; G.S., H.W., H.L., T.Z., NJ.T., and H.Y. contributed new reagents/analytic tools; Y.Y. and H.Y. analyzed data; and Y.Y. and H.Y. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: Matlab codes for iPM image processing have been deposited on GitHub and are available at https://github.com/laoyxiaoy/iPM.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1804548115/-/DCSupplemental.
Published under the PNAS license.
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Interferometric plasmonic imaging and detection of single exosomes
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