Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors

Keying Guo, Shofarul Wustoni, Anil Koklu, Escarlet Díaz-Galicia, Maximilian Moser, Adel Hama, Ahmed A. Alqahtani, Adeel Nazir Ahmad, Fatimah Saeed Alhamlan, Muhammad Shuaib, Arnab Pain, Iain McCulloch, Stefan T. Arold, Raik Grunberg, Sahika Inal

Research output: Contribution to journalArticlepeer-review

238 Scopus citations


The 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.
Original languageEnglish (US)
JournalNature Biomedical Engineering
StatePublished - May 24 2021

Bibliographical note

KAUST Repository Item: Exported on 2021-05-27
Acknowledged KAUST grant number(s): OSR-2015-CRG4-2572, OSR-2018-CARF/CCF-3079, OSR-2018-CRG7-3709, OSR-4106 CPF2019, REI/1/4204-01, REI/1/4229-01
Acknowledgements: Figure 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.


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