Towards defining reference materials for measuring extracellular vesicle refractive index, epitope abundance, size and concentration

Joshua A Welsh; Edwin van der Pol; Britta A Bettin; David R F Carter; An Hendrix; Metka Lenassi; Marc-André Langlois; Alicia Llorente; Arthur S van de Nes; Rienk Nieuwland; Vera Tang; Lili Wang; Kenneth W Witwer; Jennifer C Jones

doi:10.1080/20013078.2020.1816641

Towards defining reference materials for measuring extracellular vesicle refractive index, epitope abundance, size and concentration

J Extracell Vesicles. 2020 Sep 24;9(1):1816641. doi: 10.1080/20013078.2020.1816641.

Authors

Joshua A Welsh¹, Edwin van der Pol^{2

3

4}, Britta A Bettin^{2

4}, David R F Carter⁵, An Hendrix^{6

7}, Metka Lenassi⁸, Marc-André Langlois^{9

10

11}, Alicia Llorente¹², Arthur S van de Nes¹³, Rienk Nieuwland^{2

4}, Vera Tang^{9

10}, Lili Wang¹⁴, Kenneth W Witwer¹⁵, Jennifer C Jones¹

Affiliations

¹ Translational Nanobiology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, USA.
² Vesicle Observation Center, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
³ Biomedical Engineering & Physics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁴ Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.
⁶ Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University Hospital, Ghent, Belgium.
⁷ Cancer Research Institute Ghent, Ghent, Belgium.
⁸ Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁹ University of Ottawa Flow Cytometry and Virometry Core Facility, Ottawa, Canada.
¹⁰ Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
¹¹ Ottawa Center for Infection, Immunity and Inflammation, Ottawa, Canada.
¹² Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Norway.
¹³ VSL Dutch Metrology Institute, Delft, The Netherlands.
¹⁴ National Institute of Standards and Technology (NIST), Gaithersburg, MD, USA.
¹⁵ Departments of Molecular and Comparative Pathobiology and Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Accurate characterization of extracellular vesicles (EVs) is critical to explore their diagnostic and therapeutic applications. As the EV research field has developed, so too have the techniques used to characterize them. The development of reference materials are required for the standardization of these techniques. This work, initiated from the ISEV 2017 Biomarker Workshop in Birmingham, UK, and with further discussion during the ISEV 2019 Standardization Workshop in Ghent, Belgium, sets out to elucidate which reference materials are required and which are currently available to standardize commonly used analysis platforms for characterizing EV refractive index, epitope abundance, size and concentration. Due to their predominant use among EV researchers, a particular focus is placed on the optical methods nanoparticle tracking analysis and flow cytometry.

Keywords: Calibration; exosomes; extracellular vesicles; microvesicles; optical analysis; quality control; reference materials; standardization; validation.

Publication types

Review

Abstract

Publication types

Grants and funding