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 journalArticlepeer-review

33 Scopus citations


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 languageEnglish (US)
Article number113647
JournalBiosensors and Bioelectronics
StatePublished - Jan 1 2022


  • Antigens
  • Detection
  • Microcantilever
  • SARS-CoV-2
  • Sensitivity
  • Sensor

ASJC Scopus subject areas

  • Biophysics
  • Biotechnology
  • Biomedical Engineering
  • Electrochemistry


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