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

tetano

Editor, Senior Moderator
Nat Biomed Eng


. 2021 May 24.
doi: 10.1038/s41551-021-00734-9. Online ahead of print.
Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors


Keying Guo[SUP] #[/SUP][SUP] 1 [/SUP], Shofarul Wustoni[SUP] #[/SUP][SUP] 1 [/SUP], Anil Koklu[SUP] #[/SUP][SUP] 1 [/SUP], Escarlet Díaz-Galicia[SUP] 1 2 [/SUP], Maximilian Moser[SUP] 3 [/SUP], Adel Hama[SUP] 1 [/SUP], Ahmed A Alqahtani[SUP] 4 [/SUP], Adeel Nazir Ahmad[SUP] 5 [/SUP], Fatimah Saeed Alhamlan[SUP] 4 [/SUP], Muhammad Shuaib[SUP] 1 [/SUP], Arnab Pain[SUP] 1 [/SUP], Iain McCulloch[SUP] 3 6 [/SUP], Stefan T Arold[SUP] 7 8 9 [/SUP], Raik Grünberg[SUP] 10 11 [/SUP], Sahika Inal[SUP] 12 [/SUP]



Affiliations

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.
 
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