title: Towards traceable size determination of extracellular vesicles.
abstract: BACKGROUND
  Extracellular vesicles (EVs) have clinical importance due to their roles in a wide range of biological processes. The detection and characterization of EVs are challenging because of their small size, low refractive index, and heterogeneity.
  
  
  METHODS
  In this manuscript, the size distribution of an erythrocyte-derived EV sample is determined using state-of-the-art techniques such as nanoparticle tracking analysis, resistive pulse sensing, and electron microscopy, and novel techniques in the field, such as small-angle X-ray scattering (SAXS) and size exclusion chromatography coupled with dynamic light scattering detection.
  
  
  RESULTS
  The mode values of the size distributions of the studied erythrocyte EVs reported by the different methods show only small deviations around 130 nm, but there are differences in the widths of the size distributions.
  
  
  CONCLUSIONS
  SAXS is a promising technique with respect to traceability, as this technique was already applied for traceable size determination of solid nanoparticles in suspension. To reach the traceable measurement of EVs, monodisperse and highly concentrated samples are required.
authors: Department of Biological Nanochemistry, Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors: Zoltán
authors: Z
authors: Varga
authors: Department of Clinical Chemistry, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands.
authors: Yuana
authors: Y
authors: Yuana
authors: Department of Clinical Chemistry, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands.
authors: Anita E
authors: AE
authors: Grootemaat
authors: Department of Clinical Chemistry, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands ; Department of Biomedical Engineering and Physics, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands.
authors: Edwin
authors: E
authors: van der Pol
authors: Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany.
authors: Christian
authors: C
authors: Gollwitzer
authors: Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany.
authors: Michael
authors: M
authors: Krumrey
authors: Department of Clinical Chemistry, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands.
authors: Rienk
authors: R
authors: Nieuwland
keywords: dynamic light scattering; erythrocyte; exosome; extracellular vesicles; freeze-fracture transmission electron microscopy; microvesicle; nanoparticle tracking analysis; resistive pulse sensing; size exclusion chromatography; small-angle X-ray scattering