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 Grünberg; Sahika Inal

doi:10.1038/s41551-021-00734-9

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 Grünberg^*, Sahika Inal^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

225 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 language	English
Pages (from-to)	666-677
Number of pages	12
Journal	Nature Biomedical Engineering
Volume	5
Issue number	7
DOIs	https://doi.org/10.1038/s41551-021-00734-9
State	Published - Jul 2021
Externally published	Yes

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Guo, K., Wustoni, S., Koklu, A., Díaz-Galicia, E., Moser, M., Hama, A., Alqahtani, A. A., Ahmad, A. N., Alhamlan, F. S., Shuaib, M., Pain, A., McCulloch, I., Arold, S. T., Grünberg, R., & Inal, S. (2021). Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors. Nature Biomedical Engineering, 5(7), 666-677. https://doi.org/10.1038/s41551-021-00734-9

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

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.",

author = "Keying Guo and Shofarul Wustoni and Anil Koklu and Escarlet D{\'i}az-Galicia and Maximilian Moser and Adel Hama and Alqahtani, {Ahmed A.} and Ahmad, {Adeel Nazir} and Alhamlan, {Fatimah Saeed} and Muhammad Shuaib and Arnab Pain and Iain McCulloch and Arold, {Stefan T.} and Raik Gr{\"u}nberg and Sahika Inal",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = jul,

doi = "10.1038/s41551-021-00734-9",

language = "英语",

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Guo, K, Wustoni, S, Koklu, A, Díaz-Galicia, E, Moser, M, Hama, A, Alqahtani, AA, Ahmad, AN, Alhamlan, FS, Shuaib, M, Pain, A, McCulloch, I, Arold, ST, Grünberg, R & Inal, S 2021, 'Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors', Nature Biomedical Engineering, vol. 5, no. 7, pp. 666-677. https://doi.org/10.1038/s41551-021-00734-9

TY - JOUR

T1 - Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors

AU - Guo, Keying

AU - Wustoni, Shofarul

AU - Koklu, Anil

AU - Díaz-Galicia, Escarlet

AU - Moser, Maximilian

AU - Hama, Adel

AU - Alqahtani, Ahmed A.

AU - Ahmad, Adeel Nazir

AU - Alhamlan, Fatimah Saeed

AU - Shuaib, Muhammad

AU - Pain, Arnab

AU - McCulloch, Iain

AU - Arold, Stefan T.

AU - Grünberg, Raik

AU - Inal, Sahika

PY - 2021/7

Y1 - 2021/7

N2 - 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.

AB - 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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AN - SCOPUS:85106221161

SN - 2157-846X

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JO - Nature Biomedical Engineering

JF - Nature Biomedical Engineering

IS - 7

ER -

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

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