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

tetano

Editor, Senior Moderator
Anal Chem


. 2022 Jun 2.
doi: 10.1021/acs.analchem.2c01221. Online ahead of print.
Rapid and Sensitive Detection of Antigen from SARS-CoV-2 Variants of Concern by a Multivalent Minibinder-Functionalized Nanomechanical Sensor


Dilip Kumar Agarwal[SUP] 1 [/SUP], Andrew C Hunt[SUP] 2 [/SUP], Gajendra S Shekhawat[SUP] 1 [/SUP], Lauren Carter[SUP] 3 4 [/SUP], Sidney Chan[SUP] 3 4 [/SUP], Kejia Wu[SUP] 3 4 [/SUP], Longxing Cao[SUP] 3 4 [/SUP], David Baker[SUP] 3 4 5 [/SUP], Ramon Lorenzo-Redondo[SUP] 6 7 [/SUP], Egon A Ozer[SUP] 6 7 [/SUP], Lacy M Simons[SUP] 6 7 [/SUP], Judd F Hultquist[SUP] 6 7 [/SUP], Michael C Jewett[SUP] 2 8 9 [/SUP], Vinayak P Dravid[SUP] 1 8 9 [/SUP]



Affiliations

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.
 
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