Issue 19, 2019

An integrated microfluidic system for on-chip enrichment and quantification of circulating extracellular vesicles from whole blood

Abstract

Circulating extracellular vesicles (EVs), which can contain a wide variety of molecules such as proteins, messenger ribonucleic acids (mRNAs), micro ribonucleic acids (miRNAs) and deoxyribonucleic acids (DNAs) from cells or tissues of origin, have attracted great interest given their potential to serve as biomarkers that can be harvested in body fluids (i.e., relatively non-invasive). Since enrichment and detection of circulating EVs from whole blood have proven challenging, we report herein a fully integrated microfluidic system combining a membrane-based filtration module (i.e. pneumatically-driven microfluidic devices) and a magnetic-bead based immunoassay capable of automating blood treatment, EV enrichment, and EV quantification directly from human whole blood. Three functional modules were implemented; the first, a stirring-enhanced filtration module for separating plasma from blood cells, was characterized by a plasma recovery rate of 65%, a filtrate flow rate of 22 μL min−1, and a vesicle recovery rate of 94% within only 8 min (using 500 μL of blood). The second module, a magnetic bead-based EV enrichment device for immunocapture of circulating EVs from plasma, was characterized by a capture rate of 45%. The final module performed an on-chip enzyme-linked immunosorbent assay for plasma EV quantification in plasma. Given the automated capacity of this system, it could show promise in circulating EV research and clinical point-of-care applications.

Graphical abstract: An integrated microfluidic system for on-chip enrichment and quantification of circulating extracellular vesicles from whole blood

Supplementary files

Article information

Article type
Paper
Submitted
29 Jun 2019
Accepted
26 Aug 2019
First published
28 Aug 2019

Lab Chip, 2019,19, 3305-3315

An integrated microfluidic system for on-chip enrichment and quantification of circulating extracellular vesicles from whole blood

Y. Chen, Y. Ma, C. Chen, S. Shiesh and G. Lee, Lab Chip, 2019, 19, 3305 DOI: 10.1039/C9LC00624A

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