A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma

Devora Najjar; Josh Rainbow; Sanjay Timilsina; Pawan Jolly; Helena De Puig; Mohamed Yafia; Nolan Durr; Galit Alter; Jonathan Li; Xu Yu; David Walt; Joseph Paradiso; Pedro Estrela; James Collins; Donald E. Ingber

doi:10.1101/2021.09.01.21262387

A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma

Devora Najjar, Josh Rainbow, Sanjay Timilsina, Pawan Jolly, Helena De Puig, Mohamed Yafia, Nolan Durr, Galit Alter, Jonathan Li, Xu Yu, David Walt, Joseph Paradiso, Pedro Estrela, James Collins, Donald E. Ingber

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Abstract

Rapid, accurate and frequent detection of the RNA of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and of serological host antibodies to the virus would facilitate the determination of the immune status of individuals who have Coronavirus disease 2019 (COVID-19), were previously infected by the virus, or were vaccinated against the disease. Here we describe the development and application of a 3D-printed lab-on-a-chip that concurrently detects, via multiplexed electrochemical outputs and within 2 h, SARS-CoV-2 RNA in saliva as well as anti-SARS-CoV-2 immunoglobulins in saliva spiked with blood plasma. The device automatedly extracts, concentrates and amplifies SARS-CoV-2 RNA from unprocessed saliva, and integrates the Cas12a-based enzymatic detection of SARS-CoV-2 RNA via isothermal nucleic acid amplification with a sandwich-based enzyme-linked immunosorbent assay on electrodes functionalized with the Spike S1, nucleocapsid and receptor-binding-domain antigens of SARS-CoV-2. Inexpensive microfluidic electrochemical sensors for performing multiplexed diagnostics at the point of care may facilitate the widespread monitoring of COVID-19 infection and immunity.

Original language	English
Pages (from-to)	968-978
Number of pages	11
Journal	Nature Biomedical Engineering
Volume	6
Early online date	8 Aug 2022
DOIs	https://doi.org/10.1101/2021.09.01.21262387 https://doi.org/10.1038/s41551-022-00919-w
Publication status	Published - 31 Aug 2022

Bibliographical note

Funding: NERC GW4 FRESH CDT.

Funding

We thank T. G. Hitron, R. A. Lee and N. Weckman for helpful discussions and advice. This work was supported by the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Paul G. Allen Frontiers Group. J.R. was funded through the UK Natural Environment Research Council (NERC) GW4 FRESH CDT. H.d.P. was supported by the Harvard University Center for AIDS Research (CFAR), an NIH-funded programme (P30 AI060354), which is supported by the following NIH co-funding and participating Institutes and Centers: NIAID, NCI, NICHD, NIDCR, NHLBI, NIDA, NIMH, NIA, NIDDK, NINR, NIMHD, FIC and OAR. M.Y. acknowledges Fonds de recherche du Québec nature et technologie (FRQNT) postdoctoral fellowship no. 260284. The MGH/MassCPR COVID biorepository was supported by a gift from E. Schwartz, by the Mark and Lisa Schwartz Foundation, the Massachusetts Consortium for Pathogen Readiness, and the Ragon Institute of MGH, MIT and Harvard.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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This is a post-peer-review, pre-copyedit version of an article published in Nature Biomedical Engineering. The final authenticated version is available online at: https://doi.org/10.1038/s41551-022-00919-w
Accepted author manuscript, 8.61 MB

Cite this

Najjar, D., Rainbow, J., Timilsina, S., Jolly, P., De Puig, H., Yafia, M., Durr, N., Alter, G., Li, J., Yu, X., Walt, D., Paradiso, J., Estrela, P., Collins, J., & Ingber, D. E. (2022). A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma. Nature Biomedical Engineering, 6, 968-978. https://doi.org/10.1101/2021.09.01.21262387, https://doi.org/10.1038/s41551-022-00919-w

Najjar, D, Rainbow, J, Timilsina, S, Jolly, P, De Puig, H, Yafia, M, Durr, N, Alter, G, Li, J, Yu, X, Walt, D, Paradiso, J, Estrela, P, Collins, J & Ingber, DE 2022, 'A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma', Nature Biomedical Engineering, vol. 6, pp. 968-978. https://doi.org/10.1101/2021.09.01.21262387, https://doi.org/10.1038/s41551-022-00919-w

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abstract = "Rapid, accurate and frequent detection of the RNA of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and of serological host antibodies to the virus would facilitate the determination of the immune status of individuals who have Coronavirus disease 2019 (COVID-19), were previously infected by the virus, or were vaccinated against the disease. Here we describe the development and application of a 3D-printed lab-on-a-chip that concurrently detects, via multiplexed electrochemical outputs and within 2 h, SARS-CoV-2 RNA in saliva as well as anti-SARS-CoV-2 immunoglobulins in saliva spiked with blood plasma. The device automatedly extracts, concentrates and amplifies SARS-CoV-2 RNA from unprocessed saliva, and integrates the Cas12a-based enzymatic detection of SARS-CoV-2 RNA via isothermal nucleic acid amplification with a sandwich-based enzyme-linked immunosorbent assay on electrodes functionalized with the Spike S1, nucleocapsid and receptor-binding-domain antigens of SARS-CoV-2. Inexpensive microfluidic electrochemical sensors for performing multiplexed diagnostics at the point of care may facilitate the widespread monitoring of COVID-19 infection and immunity.",

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A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma

Abstract

Bibliographical note

Funding

UN SDGs

Access to Document

Other files and links

Fingerprint

Autolab Potentiostat & FRA32M module

Cite this

A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma

Abstract

Bibliographical note

Funding

UN SDGs

Access to Document

Other files and links

Fingerprint

Equipment

Autolab Potentiostat & FRA32M module

Cite this