Attomolar detection of hepatitis C virus core protein powered by molecular antenna-like graphene effect

Abstract

Biosensors based on graphene field-effect transistors have become a promising tool for detecting a broad range of analytes. However, they lack the stability and reproducibility required to step into biotechnological and biomedical applications. In this work, we use a controlled in-vacuum physical method for the covalent functionalization of graphene to construct ultrasensitive aptamer-based biosensors (aptasensors) able to detect hepatitis C virus core protein. These devices are highly specific and robust, achieving attomolar detection of the viral protein target in human blood plasma. The improved sensitivity is rationalized by theoretical calculations showing that induced polarization at the graphene interface caused by the proximity of covalently bound probe molecule modulates the charge balance at the graphene/molecule interface. This charge balance causes a net shift of the Dirac cone providing enhanced sensitivity towards the attomolar detection of proteins. Such an unexpected effect paves the way for using this kind of graphene-based platform for real-time diagnostics of different diseases.

Sensitivity-Enhancing Strategies of Graphene Field-Effect Transistor Biosensors for Biomarker Detection

“…This sensor detects hepatitis C virus (HCV) core proteins in human plasma with a LoD (90.9 aM), operating within a detection range from 10 −13 to 10 −18 M, with a sensitivity of 15 mV/decade. 85 The Functionalization of the Gate Electrode Surface. In the gate electrode, functionalization of GFET biosensors, gold gate electrodes are commonly chosen as a substrate for immobilizing biological receptors due to their unique properties, which include high conductivity, biocompatibility, ease of patterning, and inertness.…”

“…Reproduced with permission. 85 Copyright 2023, Biosensors and Bioelectronics. stamping and etching-free mechanical transfers, yielding graphene with minimal contaminants and a near-zero charge neutrality point.…”

“…(f) covalent functionalization strategy based on ion-sputtering in ultrahigh vacuum (UHV) and p-amino thiophenol (pATP) linker molecule. Reproduced with permission 85. Copyright 2023, Biosensors and Bioelectronics.…”