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; Joshua Rainbow; Sanjay Sharma Timilsina; Pawan Jolly; Helena de Puig; Mohamed Yafia; Nolan Durr; Hani Sallum; Galit Alter; Jonathan Z Li; Xu G Yu; David R Walt; Joseph A Paradiso; Pedro Estrela; James J Collins; Donald E Ingber

doi:10.1038/s41551-022-00919-w

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

Nat Biomed Eng. 2022 Aug;6(8):968-978. doi: 10.1038/s41551-022-00919-w. Epub 2022 Aug 8.

Authors

Devora Najjar^#^{1

2

3}, Joshua Rainbow^#^{1

4}, Sanjay Sharma Timilsina^#¹, Pawan Jolly^#¹, Helena de Puig^#^{1

2}, Mohamed Yafia¹, Nolan Durr¹, Hani Sallum¹, Galit Alter⁵, Jonathan Z Li⁶, Xu G Yu^{5

6}, David R Walt^{1

7

8}, Joseph A Paradiso³, Pedro Estrela⁴, James J Collins^{9

10

11}, Donald E Ingber^{12

13

14

15}

Affiliations

¹ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
² Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
³ MIT Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Centre for Biosensors, Bioelectronics and Biodevices (C3Bio) and Department of Electronic and Electrical Engineering, University of Bath, Bath, UK.
⁵ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
⁶ Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
⁷ Harvard Medical School, Boston, MA, USA.
⁸ Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
⁹ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. jimjc@mit.edu.
¹⁰ Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. jimjc@mit.edu.
¹¹ Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA. jimjc@mit.edu.
¹² Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.
¹³ Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.
¹⁴ Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. don.ingber@wyss.harvard.edu.
¹⁵ Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Antibodies, Viral
COVID-19* / diagnosis
Humans
Lab-On-A-Chip Devices
Plasma
RNA, Viral
SARS-CoV-2*
Saliva
Spike Glycoprotein, Coronavirus

Substances

Antibodies, Viral
RNA, Viral
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Grants and funding

P30 AI060354/AI/NIAID NIH HHS/United States