Open AccessRapid and Sensitive Detection of Antigen from SARS-CoV-2 Variants of Concern by a Multivalent Minibinder-Functionalized Nanomechanical Sensor
Author(s) -
Deepti Agarwal,
Andrew C. Hunt,
Gajendra S. Shekhawat,
Lauren Carter,
Sidney Chan,
KeJia Wu,
Longxing Cao,
David Baker,
Ramón Lorenzo-Redondo,
Egon A. Ozer,
Lacy M. Simons,
Judd F. Hultquist,
Michael C. Jewett,
Vinayak P. Dravid
Publication year - 2022
Publication title -
analytical chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.117
H-Index - 332
eISSN - 1520-6882
pISSN - 0003-2700
DOI - 10.1021/acs.analchem.2c01221
Subject(s) - chemistry , detection limit , antigen , covid-19 , coronavirus , virology , nanotechnology , chromatography , immunology , disease , infectious disease (medical specialty) , pathology , biology , medicine , materials science
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.