Porous PDMS‐Based Microsystem (ExoSponge) for Rapid Cost‐Effective Tumor Extracellular Vesicle Isolation and Mass Spectrometry‐Based Metabolic Biomarker Screening

Author:

Marvar Joseph1,Kumari Abha1,Onukwugha Nna‐Emeka1,Achreja Abhinav2,Meurs Noah2,Animasahun Olamide2,Roy Jyotirmoy2,Paserba Miya2,Raju Kruthi Srinivasa1,Fortna Shawn3,Ramnath Nithya4,Nagrath Deepak12,Kang Yoon‐Tae1ORCID,Nagrath Sunitha15ORCID

Affiliation:

1. Department of Chemical Engineering and Biointerfaces Institute University of Michigan 2800 Plymouth Road, NCRC B10‐A184 Ann Arbor MI 48109 USA

2. Department of Biomedical Engineering University of Michigan Carl A. Gerstacker Building, 2200 Bonisteel Blvd Ann Arbor MI 48109 USA

3. Department of Mechanical Engineering University of Michigan G.G. Brown Laboratory 2350 Hayward Ann Arbor MI 48109 USA

4. Department of Internal Medicine University of Michigan Ann Arbor MI 48109 USA

5. Rogel Cancer Center University of Michigan 1500 E Medical Center Dr. Ann Arbor MI 48109 USA

Abstract

AbstractPolydimethylsiloxane (PDMS) is an inexpensive robust polymer that is commonly used as the fundamental fabrication material for soft‐lithography‐based microfluidic devices. Owing to its versatile material properties, there are some attempts to use PDMS as a porous 3D structure for sensing. However, reliable and easy fabrication has been challenging along with the inherent hydrophobic nature of PDMS hindering its use in biomedical sensing applications. Herein, a cleanroom‐free inexpensive method to create 3D porous PDMS structures, “ExoSponge” and the effective surface modification to functionalize its 3D porous structure is reported. The ability of ExoSponge to recover cancer‐associated extracellular vesicles (EVs) from complex biological samples of up to 10 mL in volume is demonstrated. When compared to ultracentrifugation, the ExoSponge showes a significant increase in cancer EV isolation of more than 210%. Targeted ultra‐high pressure liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) is further employed to profile 70 metabolites in the EVs recovered from the lung cancer patient's plasma. The resulting profiles reveal the potential intraexosomal metabolite biomarker, phenylacetylglutamine (PAG), in non‐small cell lung cancer. The high sensitivity, simple usage, and cost‐effectiveness of the ExoSponge platform creates huge potential for rapid, economical and yet specific isolation of exosomes enabling future diagnostic applications of EVs in cancers.

Funder

National Science Foundation

Publisher

Wiley

Subject

Industrial and Manufacturing Engineering,Mechanics of Materials,General Materials Science

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