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

Authors
  • Agarwal, Dilip Kumar1
  • Nandwana, Vikas1
  • Henrich, Stephen E.2
  • Josyula, Vara Prasad V.N.3
  • Thaxton, C. Shad2
  • Qi, Chao4
  • Simons, Lacy M.5, 6
  • Hultquist, Judd F.5, 6
  • Ozer, Egon A.5, 6
  • Shekhawat, Gajendra S.1
  • Dravid, Vinayak P.1
  • 1 Center, Northwestern University, Evanston, IL, 60208, USA
  • 2 Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
  • 3 Cleveland Clinic, Lerner Research Institute, Cleveland, OH, 44195, USA
  • 4 Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
  • 5 Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
  • 6 Center for Pathogen Genomics and Microbial Evolution, Institute for Global Health, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
Type
Published Article
Journal
Biosensors & Bioelectronics
Publisher
Elsevier B.V.
Publication Date
Sep 17, 2021
Volume
195
Pages
113647–113647
Identifiers
DOI: 10.1016/j.bios.2021.113647
PMID: 34583103
PMCID: PMC8445766
Source
PubMed Central
Keywords
Disciplines
  • Article
License
Unknown

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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