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SARS-CoV-2 multi-variant rapid detector based on graphene transistor functionalized with an engineered dimeric ACE2
Alice Romagnoli1,2,3, Mattia D'Agostino1, Eleonora Pavoni4
1Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy.
Nano Today
|December 20, 2022
Summary
A new graphene biosensor detects SARS-CoV-2 variants by targeting the Spike-ACE2 interaction. This rapid, sensitive point-of-care test works on various strains, including Omicron, in clinical samples.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Infectious Disease Diagnostics
Background:
- Reliable point-of-care (POC) rapid tests are essential for controlling Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spread.
- Emerging SARS-CoV-2 variants of concern (VOC) can evade current diagnostic antibody-based tests due to reduced binding affinity.
- The Spike-ACE2 interaction is critical for viral entry, presenting a potential target for robust diagnostics.
Purpose of the Study:
- To develop a highly sensitive and variant-robust biosensor for SARS-CoV-2 detection.
- To exploit the Spike-ACE2 interaction for improved diagnostic efficacy against evolving viral strains.
- To create a miniaturized, reusable point-of-care system for rapid SARS-CoV-2 identification.
Main Methods:
- Computational analysis to design a chimeric ACE2-Fragment crystallizable (ACE2-Fc) construct mimicking the native ACE2 dimeric conformation.
- Functionalization of graphene field-effect transistors (gFETs) with the ACE2-Fc construct.
- In vitro and clinical sample testing of the gFET biosensor against various SARS-CoV-2 variants.
Main Results:
- The ACE2-Fc construct effectively mimics the native ACE2 receptor conformation.
- gFET biosensors functionalized with ACE2-Fc achieved a sensitivity of 20 pg/mL for the trimeric Spike protein.
- The biosensor successfully detected multiple SARS-CoV-2 variants (B.1.610, Alpha, Beta, Gamma, Delta, Omicron sub-lineages) in clinical nasopharyngeal swabs.
- A Limit of Detection (LOD) of 65 cps/mL was achieved for Omicron BA.5 in swab specimens.
Conclusions:
- The developed gFET biosensor offers a sensitive, rapid, and reusable platform for SARS-CoV-2 detection.
- This approach demonstrates robustness against various SARS-CoV-2 variants, addressing limitations of current antibody-based tests.
- The Spike-ACE2 interaction-based biosensor represents a promising advancement for point-of-care diagnostics in managing infectious diseases.
