Automated Label‐Free Assay for Viral Detection and Inhibitor Screening via Biomembrane‐Functionalized Microelectrode Arrays
Abstract
Abstract Most virus infection assays have indirect readout such as virus number following entry (e.g., PCR, cell lysis). While effective, these technologies are labor‐intensive, require specialized environments (e.g., sterile or RNA‐free), and detect later‐stage viral events like lysis or cell death, lacking sensitivity to early fusion events. To address these limitations, we present biologically relevant 2D membrane materials, host‐cell‐derived supported lipid bilayers (hcd‐SLBs), integrated with organic microelectrode arrays (OMEAs) for detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) fusion. By overexpressing angiotensin‐converting enzyme 2 (ACE2) receptors on the native membranes, the platform functions as a viral sensor capable of detecting virus pseudo particles (VPPs) through the late pathway. Additionally, hcd‐SLBs extracted from human lung epithelium expressing native ACE2 detect fusion events through the early pathway. The platform's utility as a drug‐screening tool is demonstrated by testing antibodies targeting either the ACE2 on the host membrane or the viral spike (S) proteins. To enhance the throughput, microfluidics are integrated for automation and OMEAs are incorporated within each channel, miniaturizing the testing units. This system supports high‐throughput data generation, automation, and scalability, providing an efficient platform for viral fusion detection that advances the study of pathogen‐host interactions and accelerates antiviral drug discovery.
Article Details
Authors (18)
Zixuan Lu
Jeremy Treiber
Department of Materials Science and Engineering Stanford University Stanford CA 94305 USA
Konstantinos Kallitsis
Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK
Ekaterina Selivanovitch
Robert F. Smith School of Chemical and Biomolecular Engineering Cornell University Ithaca NY 14853 USA
Alexandra Wheeler
Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK
Maria Lopez‐Cavestany
Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK
Zhongmou Chao
Robert F. Smith School of Chemical and Biomolecular Engineering Cornell University Ithaca NY 14853 USA
Sarah L Barron
Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK
Ju An Park
Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK
Darius Hoven
Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK
Anna Scheeder
Department of Chemical Engineering & Biotechnology University of Cambridge Cambridge UK
Aimee Withers
Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK
Becky M. Hess
Pacific Northwest National Laboratory 902 Battelle Boulevard Richland WA 99 354 USA
Clemens F. Kaminski
Department of Chemical Engineering and Biotechnology
Alberto Salleo
Anna‐Maria Pappa
Department of Biomedical Engineering Khalifa University of Science and Technology Abu Dhabi 127788 UAE
Susan Daniel
Róisín M Owens
Department of Chemical Engineering and Biotechnology University of Cambridge Philippa Fawcett Drive Cambridge CB3 0AS UK