Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors
Alqahtani, Ahmed A.
Ahmad, Adeel Nazir
Alhamlan, Fatimah Saeed
Arold, Stefan T.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
KAUST Health, Thuwal, Saudi Arabia.
Chemical Science Program
KAUST Solar Center (KSC)
Physical Science and Engineering (PSE) Division
Computational Bioscience Research Center (CBRC)
KAUST Grant NumberOSR-2015-CRG4-2572
Embargo End Date2021-11-24
Permanent link to this recordhttp://hdl.handle.net/10754/669265
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AbstractThe coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid and sensitive protein detection and quantification in simple and robust formats for widespread point-of-care applications. Here, we report on nanobody-functionalized organic electrochemical transistors with a modular architecture for the rapid quantification of single-molecule-to-nanomolar levels of specific antigens in complex bodily fluids. The sensors combine a solution-processable conjugated polymer in the transistor channel and high-density and orientation-controlled bioconjugation of nanobody–SpyCatcher fusion proteins on disposable gate electrodes. The devices provide results after 10 min of exposure to 5 μl of unprocessed samples, maintain high specificity and single-molecule sensitivity in human saliva and serum, and can be reprogrammed to detect any protein antigen if a corresponding specific nanobody is available. We used the sensors to detect green fluorescent protein, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV) spike proteins, and for the COVID-19 screening of unprocessed clinical nasopharyngeal swab and saliva samples with a wide range of viral loads.
CitationGuo, K., Wustoni, S., Koklu, A., Díaz-Galicia, E., Moser, M., Hama, A., … Inal, S. (2021). Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors. Nature Biomedical Engineering. doi:10.1038/s41551-021-00734-9
SponsorsFigure 1 was produced by X. Pita, a scientific illustrator at KAUST. We thank all of the members of the KAUST Rapid Research Response Team (R3T) for COVID-19, especially S. Hamdan, for contributions in this study. We thank S. Mfarrej and A. K. Subudhi for providing access to and assisting with the experiments in the Biosafety Level 2+ experimental room at KAUST. We thank the KAUST Health team (operated by Dr. Soliman Fakeeh Hospital, Jeddah), including D. Buttigieg and M. Habib, for providing clinical samples. We thank staff at the King Faisal Specialist Hospital and Research Center (Riyadh), particularly A. Alzahrani, M. Alsanea and F. Alhadeq, for help with organizing and hosting some of the clinical studies. We thank the KAUST nanofabrication core laboratory team, D. Rosas Villalva and U. Buttner for help with device fabrication and integration. This work was initiated thanks to the KAUST Impact Acceleration Fund (IAF) program. The research reported in this publication was supported by funding from the Office of Sponsored Research (OSR) at KAUST under award numbers REI/1/4204-01, REI/1/4229-01, OSR-2018-CRG7-3709, OSR-2018-CARF/CCF-3079, OSR-2015-CRG4-2572 and OSR-4106 CPF2019. We acknowledge EC FP7 Project SC2 (610115), EC H2020 (643791) and EPSRC Projects EP/G037515/1, EP/M005143/1 and EP/L016702/1.
PublisherSpringer Science and Business Media LLC
JournalNature Biomedical Engineering