期刊
ANALYTICAL CHEMISTRY
卷 94, 期 23, 页码 8105-8109出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.2c01221
关键词
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资金
- Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource [NSF-ECCS-1542205]
- MRSEC Program at the Materials Research Center [NSF DMR-1121262]
- International Institute for Nanotechnology (IIN)
- Keck Foundation
- State of Illinois, through the IIN
- National Heart, Lung and Blood Institute [1400-SUB/3U54HL119810-07S1]
- National Defense Science and Engineering Graduate (NDSEG) Fellowship Program [NDSEG-36373]
- Packard Foundation
- Defense Threat Reduction Agency [HDTRA-12-01-0004, HDTRA-12-11-0038]
- National Science Foundation Rapid [MCB-2028651]
- Office of the Provost
- Office for Research
- Northwestern University Information Technology
- Dixon Translational Research Grant by Dixon Family Foundation
- Northwestern Center for Advanced Technologies (NUCATS)
- CTSA supplement [NCATS UL1 TR002389]
- Northwestern University Cancer Center [P30 CA060553]
- NIH [U19 AI135964, P30 AI117943, R21 AI163912]
- Walder Foundation Foundation's Chicago Coronavirus Assessment Network (Chicago CAN) Initiative
This study reports the development of a nanomechanical sensor-based platform for rapid and sensitive detection of SARS-CoV-2 variants. The sensor utilizes computationally designed multivalent minibinders immobilized on a microcantilever surface, demonstrating high sensitivity and rapid detection. Clinical validation of the sensor shows detection of antigens from the Omicron (BA-1) variant.
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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