Absolute sizing and label-free identification of extracellular vesicles by flow cytometry

Edwin van der Pol*, Leonie de Rond, Frank A.W. Coumans, Elmar L. Gool, Anita N. Böing, Auguste Sturk, Rienk Nieuwland, Ton G. van Leeuwen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

114 Citations (Scopus)
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Abstract

Blood contains extracellular vesicles (EVs), which are biological nanoparticles with clinical applications. In blood plasma, EVs are outnumbered by similar-sized lipoprotein particles (LPs), leading to controversial data such as non-specific binding of antibodies to LPs. Flow cytometry is a clinically applicable technique to characterize single EVs in body fluids. However, flow cytometry data have arbitrary units, impeding standardization, data comparison, and data interpretation, such as differentiation between EVs and LPs. Here we present a new method, named flow cytometry scatter ratio (Flow-SR), to relate the ambiguous light scattering signals of flow cytometry to the diameter and refractive index (RI) of single nanoparticles between 200-500 nm in diameter. Flow-SR enables label-free differentiation between EVs and LPs and improves data interpretation and comparison. Because Flow-SR is easy to implement, widely applicable, and more accurate and faster than existing techniques to size nanoparticles in suspension, Flow-SR has numerous applications in nanomedicine.

Original languageEnglish
Pages (from-to)801-810
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number3
DOIs
Publication statusPublished - Apr 2018
Externally publishedYes

Keywords

  • Drug delivery
  • exosomes
  • extracellular vesicles
  • flow cytometry
  • nanomedicine
  • nanoparticles

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