Ultrasensitive detection of SARS-CoV-2 spike protein by graphene field-effect transistors

Alessandro Silvestri; Julian Zayas-Arrabal; Mariano Vera-Hidalgo; Desire Di Silvio; Cecilia Wetzl; Marta Martinez-Moro; Amaia Zurutuza; Elias Torres; Alba Centeno; Arantxa Maestre; Juan Manuel Gómez; María Arrastua; Marta Elicegui; Nerea Ontoso; Maurizio Prato; Ivan Coluzza; Alejandro Criado

doi:10.1039/D2NR05103F

Ultrasensitive detection of SARS-CoV-2 spike protein by graphene field-effect transistors†

Alessandro Silvestri,

‡^a Julian Zayas-Arrabal,

‡§^a Mariano Vera-Hidalgo,^a Desire Di Silvio,^a Cecilia Wetzl,

^ab Marta Martinez-Moro,^a Amaia Zurutuza,^c Elias Torres,^c Alba Centeno,^c Arantxa Maestre,^c Juan Manuel Gómez,^c María Arrastua,^c Marta Elicegui,^c Nerea Ontoso,^c Maurizio Prato,

*^ade Ivan Coluzza*^fe and Alejandro Criado

*^ag

Author affiliations

* Corresponding authors

^a Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 194, 20014 Donostia-San Sebastián, Spain
E-mail: mprato@cicbiomagune.es

^b University of the Basque Country UPV-EHU, 20018 Donostia-San Sebastián, Spain

^c Graphenea Semiconductor SLU., Paseo Mikeletegi 83, 20009 San Sebastián, Spain

^d Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 3412 7 Trieste, Italy

^e Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain

^f BCMaterials, Basque Center for Materials, Applications and Nanostructures, Bld. Martina Casiano, UPV/EHU Science Park, Barrio Sarriena s/n, 48940 Leioa, Spain
E-mail: ivan.coluzza@bcmaterials.net

^g Universidade da Coruña, CICA – Centro Interdisciplinar de Química e Bioloxía, Rúa as Carballeiras, 15071 A Coruña, Spain
E-mail: a.criado@udc.es

Abstract

COVID-19, caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), originated a global health crisis, causing over 2 million casualties and altering human daily life all over the world. This pandemic emergency revealed the limitations of current diagnostic tests, highlighting the urgency to develop faster, more precise and sensitive sensors. Graphene field effect transistors (GFET) are analytical platforms that enclose all these requirements. However, the design of a sensitive and robust GFET is not a straightforward objective. In this work, we report a GFET array biosensor for the detection of SARS-CoV-2 spike protein using the human membrane protein involved in the virus internalisation: angiotensin-converting enzyme 2 (ACE2). By finely controlling the graphene functionalisation, by tuning the Debye length, and by deeply characterising the ACE2-spike protein interactions, we have been able to detect the target protein with an extremely low limit of detection (2.94 aM). This work set the basis for a new class of analytical platforms, based on human membrane proteins, with the potential to detect a broad variety of pathogens, even before their isolation, being a powerful tool in the fight against future pandemics.

This article is part of the themed collection: Nanoscale 2023 Emerging Investigators

Nanoscale

Ultrasensitive detection of SARS-CoV-2 spike protein by graphene field-effect transistors†

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Ultrasensitive detection of SARS-CoV-2 spike protein by graphene field-effect transistors

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