TY - JOUR
T1 - Rapid and Sensitive Detection of Antigen from SARS-CoV-2 Variants of Concern by a Multivalent Minibinder-Functionalized Nanomechanical Sensor
AU - Agarwal, Dilip Kumar
AU - Hunt, Andrew C.
AU - Shekhawat, Gajendra S.
AU - Carter, Lauren
AU - Chan, Sidney
AU - Wu, Kejia
AU - Cao, Longxing
AU - Baker, David
AU - Lorenzo-Redondo, Ramon
AU - Ozer, Egon A.
AU - Simons, Lacy M.
AU - Hultquist, Judd F.
AU - Jewett, Michael C.
AU - Dravid, Vinayak P.
N1 - Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/6/14
Y1 - 2022/6/14
N2 - 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.
AB - 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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U2 - 10.1021/acs.analchem.2c01221
DO - 10.1021/acs.analchem.2c01221
M3 - Article
C2 - 35652578
AN - SCOPUS:85131964569
SN - 0003-2700
VL - 94
SP - 8105
EP - 8109
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 23
ER -