Highly sensitive and ultra-rapid antigen-based detection of SARS-CoV-2 using nanomechanical sensor platform

Dilip Kumar Agarwal; Vikas Nandwana; Stephen E. Henrich; Vara Prasad V.N. Josyula; C. Shad Thaxton; Chao Qi; Lacy M. Simons; Judd F. Hultquist; Egon A. Ozer; Gajendra S. Shekhawat; Vinayak P. Dravid

doi:10.1016/j.bios.2021.113647

Highly sensitive and ultra-rapid antigen-based detection of SARS-CoV-2 using nanomechanical sensor platform

Dilip Kumar Agarwal, Vikas Nandwana, Stephen E. Henrich, Vara Prasad V.N. Josyula, C. Shad Thaxton, Chao Qi, Lacy M. Simons, Judd F. Hultquist, Egon A. Ozer, Gajendra S. Shekhawat^*, Vinayak P. Dravid^*

^*Corresponding author for this work

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

49 Scopus citations

Abstract

The rapid spread of COVID-19 including recent emergence of new variants with its extreme range of pathologies create an urgent need to develop a versatile sensor for a rapid, precise, and highly sensitive detection of SARS-CoV-2. Herein, we report a microcantilever-based optical detection of SARS-CoV-2 antigenic proteins in just few minutes with high specificity by employing fluidic-atomic force microscopy (f-AFM) mediated nanomechanical deflection method. The corresponding antibodies against the target antigens were first grafted on the gold-coated microcantilever surface pre-functionalized with EDC-NHS chemistry for a suitable antibody-antigen interaction. Rapid detection of SARS-CoV-2 nucleocapsid (N) and spike (S1) receptor binding domain (RBD) proteins was first demonstrated at a clinically relevant concentration down to 1 ng/mL (33 pM) by real-time monitoring of nanomechanical signal induced by antibody-antigen interaction. More importantly, we further show high specific detection of antigens with nasopharyngeal swab specimens from patients pre-determined with qRT-PCR. The results take less than 5 min (swab to signal ≤5 min) and exhibit high selectivity and analytical sensitivity (LoD: 100 copies/ ml; 0.71 ng/ml of N protein). These findings demonstrate potential for nanomechanical signal transduction towards rapid antigen detection for early screening of SARS-CoV-2 and its related mutants.

Original language	English (US)
Article number	113647
Journal	Biosensors and Bioelectronics
Volume	195
DOIs	https://doi.org/10.1016/j.bios.2021.113647
State	Published - Jan 1 2022

Funding

Sample collection was supported by a COVID-19 pilot grant from the Northwestern University Clinical and Translational Science Institute (NUCATS, NIH grant UL1 TR001422 ); a Dixon Translational Research Grant made possible by the generous support of the Dixon Family Foundation ; a CTSA supplement to NCATS UL1 TR002389 ; and a supplement to the Northwestern University Cancer Center P30 CA060553 (J.F.H., E.A.O.). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation and National Institutes of Health. Corresponding authors have intellectual property related to the diagnostic platform. This work made use of the SPID facilities of the NUANCE Center at Northwestern University which has received support from Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF-ECCS-1542205), MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. This work was supported by grant from the National Heart, Lung and Blood Institute Award Number 1400-SUB/3U54HL119810-07S1: Rapid Diagnostics of SARS-C0V-2 of Asymptomatic people returning to work and school. Sample collection was supported by a COVID-19 pilot grant from the Northwestern University Clinical and Translational Science Institute (NUCATS, NIH grant UL1 TR001422); a Dixon Translational Research Grant made possible by the generous support of the Dixon Family Foundation; a CTSA supplement to NCATS UL1 TR002389; and a supplement to the Northwestern University Cancer Center P30 CA060553 (J.F.H. E.A.O.). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation and National Institutes of Health. Corresponding authors have intellectual property related to the diagnostic platform. This work made use of the SPID facilities of the NUANCE Center at Northwestern University which has received support from Soft and Hybrid Nanotechnology Experimental (SH y NE) Resource ( NSF-ECCS-1542205 ), MRSEC program ( NSF DMR-1121262 ) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. This work was supported by grant from the National Heart, Lung and Blood Institute Award Number 1400-SUB/3U54HL119810-07S1 : Rapid Diagnostics of SARS-C0V-2 of Asymptomatic people returning to work and school.

Keywords

Antigens
Detection
Microcantilever
SARS-CoV-2
Sensitivity
Sensor

ASJC Scopus subject areas

Biotechnology
Biophysics
Biomedical Engineering
Electrochemistry

UN SDGs

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

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10.1016/j.bios.2021.113647

Cite this

Agarwal, D. K., Nandwana, V., Henrich, S. E., Josyula, V. P. V. N., Thaxton, C. S., Qi, C., Simons, L. M., Hultquist, J. F., Ozer, E. A., Shekhawat, G. S., & Dravid, V. P. (2022). Highly sensitive and ultra-rapid antigen-based detection of SARS-CoV-2 using nanomechanical sensor platform. Biosensors and Bioelectronics, 195, Article 113647. https://doi.org/10.1016/j.bios.2021.113647

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abstract = "The rapid spread of COVID-19 including recent emergence of new variants with its extreme range of pathologies create an urgent need to develop a versatile sensor for a rapid, precise, and highly sensitive detection of SARS-CoV-2. Herein, we report a microcantilever-based optical detection of SARS-CoV-2 antigenic proteins in just few minutes with high specificity by employing fluidic-atomic force microscopy (f-AFM) mediated nanomechanical deflection method. The corresponding antibodies against the target antigens were first grafted on the gold-coated microcantilever surface pre-functionalized with EDC-NHS chemistry for a suitable antibody-antigen interaction. Rapid detection of SARS-CoV-2 nucleocapsid (N) and spike (S1) receptor binding domain (RBD) proteins was first demonstrated at a clinically relevant concentration down to 1 ng/mL (33 pM) by real-time monitoring of nanomechanical signal induced by antibody-antigen interaction. More importantly, we further show high specific detection of antigens with nasopharyngeal swab specimens from patients pre-determined with qRT-PCR. The results take less than 5 min (swab to signal ≤5 min) and exhibit high selectivity and analytical sensitivity (LoD: 100 copies/ ml; 0.71 ng/ml of N protein). These findings demonstrate potential for nanomechanical signal transduction towards rapid antigen detection for early screening of SARS-CoV-2 and its related mutants.",

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doi = "10.1016/j.bios.2021.113647",

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AU - Agarwal, Dilip Kumar

AU - Nandwana, Vikas

AU - Henrich, Stephen E.

AU - Josyula, Vara Prasad V.N.

AU - Thaxton, C. Shad

AU - Qi, Chao

AU - Simons, Lacy M.

AU - Hultquist, Judd F.

AU - Ozer, Egon A.

AU - Shekhawat, Gajendra S.

AU - Dravid, Vinayak P.

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N2 - The rapid spread of COVID-19 including recent emergence of new variants with its extreme range of pathologies create an urgent need to develop a versatile sensor for a rapid, precise, and highly sensitive detection of SARS-CoV-2. Herein, we report a microcantilever-based optical detection of SARS-CoV-2 antigenic proteins in just few minutes with high specificity by employing fluidic-atomic force microscopy (f-AFM) mediated nanomechanical deflection method. The corresponding antibodies against the target antigens were first grafted on the gold-coated microcantilever surface pre-functionalized with EDC-NHS chemistry for a suitable antibody-antigen interaction. Rapid detection of SARS-CoV-2 nucleocapsid (N) and spike (S1) receptor binding domain (RBD) proteins was first demonstrated at a clinically relevant concentration down to 1 ng/mL (33 pM) by real-time monitoring of nanomechanical signal induced by antibody-antigen interaction. More importantly, we further show high specific detection of antigens with nasopharyngeal swab specimens from patients pre-determined with qRT-PCR. The results take less than 5 min (swab to signal ≤5 min) and exhibit high selectivity and analytical sensitivity (LoD: 100 copies/ ml; 0.71 ng/ml of N protein). These findings demonstrate potential for nanomechanical signal transduction towards rapid antigen detection for early screening of SARS-CoV-2 and its related mutants.

AB - The rapid spread of COVID-19 including recent emergence of new variants with its extreme range of pathologies create an urgent need to develop a versatile sensor for a rapid, precise, and highly sensitive detection of SARS-CoV-2. Herein, we report a microcantilever-based optical detection of SARS-CoV-2 antigenic proteins in just few minutes with high specificity by employing fluidic-atomic force microscopy (f-AFM) mediated nanomechanical deflection method. The corresponding antibodies against the target antigens were first grafted on the gold-coated microcantilever surface pre-functionalized with EDC-NHS chemistry for a suitable antibody-antigen interaction. Rapid detection of SARS-CoV-2 nucleocapsid (N) and spike (S1) receptor binding domain (RBD) proteins was first demonstrated at a clinically relevant concentration down to 1 ng/mL (33 pM) by real-time monitoring of nanomechanical signal induced by antibody-antigen interaction. More importantly, we further show high specific detection of antigens with nasopharyngeal swab specimens from patients pre-determined with qRT-PCR. The results take less than 5 min (swab to signal ≤5 min) and exhibit high selectivity and analytical sensitivity (LoD: 100 copies/ ml; 0.71 ng/ml of N protein). These findings demonstrate potential for nanomechanical signal transduction towards rapid antigen detection for early screening of SARS-CoV-2 and its related mutants.

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KW - Sensitivity

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Highly sensitive and ultra-rapid antigen-based detection of SARS-CoV-2 using nanomechanical sensor platform

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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