Ultrasensitive Real-Time Detection of SARS-CoV-2 Proteins with Arrays of Biofunctionalized Graphene Field-Effect Transistors

TL;DR

This paper introduces a novel microfluidic and electronic platform for real-time, multiplexed detection of SARS-CoV-2 proteins using biofunctionalized graphene FETs, achieving ultrasensitive detection limits and broad dynamic range.

Contribution

It presents a new integrated system combining microfluidics, electronics, and biofunctionalized graphene FETs for highly sensitive, multiplexed, real-time biosensing of viral proteins.

Findings

Detection limit of 10 aM for SARS-CoV-2 proteins

Parallel measurement of 15 GFETs on a single chip

Dynamic range spanning four orders of magnitude

Abstract

With the growing interest in graphene field-effect transistors (GFETs) for biosensing applications, there is a strong demand for strategies enabling flexible and multiplexed biofunctionalization, as well as highly parallel, real-time electronic readout integrated with microfluidic control. Here we present a methodology that addresses these challenges by enabling real-time, parallel monitoring of multiple GFETs integrated on a single microfabricated chip within an automated electronic and microfluidic platform. We demonstrate the capabilities of this approach through ultrasensitive detection of the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. GFET chips are functionalized via van der Waals assembly using 1 nm-thick molecular two-dimensional (2D) materials - carbon nanomembranes - which enable multiplexed biofunctionalization. The chips are integrated into a custom-developed microelectronic and microfluidic system that allows parallel, real-time, and automated measurements of 15 GFETs. We present in situ biofunctionalization of the GFETs with antibodies, followed by highly specific detection of the S- and N-proteins with limits of detection down to 10 aM and a dynamic range spanning four orders of magnitude. Owing to its versatility, the presented methodology is readily adaptable for sensing a wide range of biological and chemical targets.