Microfluidic Size Exclusion Chromatography (μSEC) for Extracellular Vesicles and Plasma Protein Separation.

blood extracellular vesicles microfluidic miniaturization size exclusion chromatography

Journal

Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338

Informations de publication

Date de publication:
02 2022
Historique:
revised: 02 12 2021
received: 28 07 2021
pubmed: 6 1 2022
medline: 19 3 2022
entrez: 5 1 2022
Statut: ppublish

Résumé

Extracellular vesicles (EVs) are recognized as next generation diagnostic biomarkers due to their disease-specific biomolecular cargoes and importance in cell-cell communications. A major bottleneck in EV sample preparation is the inefficient and laborious isolation of nanoscale EVs (≈50-200 nm) from endogenous proteins in biological samples. Herein, a unique microfluidic platform is reported for EV-protein fractionation based on the principle of size exclusion chromatography (SEC). Using a novel rapid (≈20 min) replica molding technique, a fritless microfluidic SEC device (μSEC) is fabricated using thiol-ene polymer (UV glue NOA81, Young's modulus ≈1 GPa) for high pressure (up to 6 bar) sample processing. Controlled on-chip nanoliter sample plug injection (600 nL) using a modified T-junction injector is first demonstrated with rapid flow switching response time (<1.5 s). Device performance is validated using fluorescent nanoparticles (50 nm), albumin, and breast cancer cells (MCF-7)-derived EVs. As a proof-of-concept for clinical applications, EVs are directly isolated from undiluted human platelet-poor plasma using μSEC and show distinct elution profiles between EVs and proteins based on nanoparticle particle analysis (NTA), Western blot and flow cytometry analysis. Overall, the optically transparent μSEC can be readily automated and integrated with EV detection assays for EVs manufacturing and clinical diagnostics.

Identifiants

pubmed: 34984816
doi: 10.1002/smll.202104470
doi:

Substances chimiques

Blood Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2104470

Informations de copyright

© 2022 Wiley-VCH GmbH.

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Auteurs

Sheng Yuan Leong (SY)

School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.

Hong Boon Ong (HB)

School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.

Hui Min Tay (HM)

School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.

Fang Kong (F)

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.

Megha Upadya (M)

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.

Lingyan Gong (L)

School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.

Ming Dao (M)

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
Department of Material Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.

Rinkoo Dalan (R)

Endocrine and Diabetes, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Clinical Sciences Building, Singapore, 308232, Singapore.

Han Wei Hou (HW)

School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Clinical Sciences Building, Singapore, 308232, Singapore.

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