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

11 Scopus citations

Abstract

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
DOIs
StatePublished - May 24 2021

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