Microfluidic approaches for isolation, detection, and characterization of extracellular vesicles

Extracellular vesicles (EVs) are cell-derived vesicles present in body fluids that play an essential role in various cellular processes, such as intercellular communication, inflammation, cellular homeostasis, survival, transport, and regeneration. Their isolation and analysis from body fluids have a great clinical potential to provide information on a variety of disease states such as cancer, cardiovascular complications and inflammatory disorders. Despite increasing scientific and clinical interest in this field, there are still no standardized procedures available for the purification, detection, and characterization of EVs. Advances in microfluidics allow for chemical sampling with increasingly high spatial resolution and under precise manipulation down to single molecule level. Researchers from Utrecht University overview the working principle and examples of the isolation and detection methods with the potential to be used for extracellular vesicles and highlight the integrated on-chip systems for isolation and characterization of EVs.

Heterogeneous EVs populations separated using microfluidic systems
based on their intrinsic (passive) and extrinsic (dynamic) characteristics.


(A) Dielectrophoresis (DEP)-based approach in which EVs are exposed to a non-uniform electric field and EVs are separated based on the difference between the DEP (FDEP) and (Fgrav) gravitational forces. (B) The hydrodynamic-based method that utilizes the competing hydrodynamic wall lift force (FL) and a shear gradient lift force (FS). (C) The immunoaffinitybased technique that depend on the interaction of cell surface molecules (red) with antibodies or other ligands (blue) functionalized on the channel surface. (D) Magnetic-based technique: an applied magnetic field is used to deflect and focus cells labeled with magnetic particles (green).

Gholizadeh S, Shehata Draz M, Zarghooni M, Sanati-Nezhad A, Ghavami S, Shafiee H, Akbari M. (2017) Microfluidic approaches for isolation, detection, and characterization of extracellular vesicles: Current status and future directions. Biosens Bioelectron [Epub ahead of print]. [abstract]

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