Rapid and Sensitive Detection of Antigen from SARS-CoV-2 Variants of Concern by a Multivalent Minibinder-Functionalized Nanomechanical Sensor

Dilip Kumar Agarwal, Andrew C. Hunt, Gajendra S. Shekhawat, Lauren Carter, Sidney Chan, Kejia Wu, Longxing Cao, David Baker, Ramon Lorenzo-Redondo, Egon A. Ozer, Lacy M. Simons, Judd F. Hultquist, Michael C. Jewett, Vinayak P. Dravid*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

New platforms for the rapid and sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern are urgently needed. Here we report the development of a nanomechanical sensor based on the deflection of a microcantilever capable of detecting the SARS-CoV-2 spike (S) glycoprotein antigen using computationally designed multivalent minibinders immobilized on a microcantilever surface. The sensor exhibits rapid (<5 min) detection of the target antigens down to concentrations of 0.05 ng/mL (362 fM) and is more than an order of magnitude more sensitive than an antibody-based cantilever sensor. Validation of the sensor with clinical samples from 33 patients, including 9 patients infected with the Omicron (BA.1) variant observed detection of antigen from nasopharyngeal swabs with cycle threshold (Ct) values as high as 39, suggesting a limit of detection similar to that of the quantitative reverse transcription polymerase chain reaction (RT-qPCR). Our findings demonstrate the use of minibinders and nanomechanical sensors for the rapid and sensitive detection of SARS-CoV-2 and potentially other disease markers.

Original languageEnglish (US)
Pages (from-to)8105-8109
Number of pages5
JournalAnalytical Chemistry
Volume94
Issue number23
DOIs
StatePublished - Jun 14 2022

ASJC Scopus subject areas

  • Analytical Chemistry

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