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

Yi Sin Chen, Yu Dong Ma, Chihchen Chen, Shu Chu Shiesh, Gwo Bin Lee

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3305-3315
Number of pages11
JournalLab on a Chip
Volume19
Issue number19
DOIs
Publication statusPublished - 2019 Jan 1

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Microfluidics
Blood
Plasmas
RNA
Lab-On-A-Chip Devices
Recovery
Immunosorbents
Body fluids
Biomarkers
Point-of-Care Systems
Assays
DNA
Enzymes
Cells
Flow rate
Extracellular Vesicles
Tissue
Body Fluids
Proteins
Membranes

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

Cite this

Chen, Yi Sin ; Ma, Yu Dong ; Chen, Chihchen ; Shiesh, Shu Chu ; Lee, Gwo Bin. / An integrated microfluidic system for on-chip enrichment and quantification of circulating extracellular vesicles from whole blood. In: Lab on a Chip. 2019 ; Vol. 19, No. 19. pp. 3305-3315.
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An integrated microfluidic system for on-chip enrichment and quantification of circulating extracellular vesicles from whole blood. / Chen, Yi Sin; Ma, Yu Dong; Chen, Chihchen; Shiesh, Shu Chu; Lee, Gwo Bin.

In: Lab on a Chip, Vol. 19, No. 19, 01.01.2019, p. 3305-3315.

Research output: Contribution to journalArticle

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