Graphene-Based Electronic Immunosensor with Femtomolar Detection Limit in Whole Serum

Abstract

Purely electronic diagnostic devices that are sensitive to biomolecules' intrinsic charge present a very attractive platform for point-of-care (PoC) applications, since they can operate under label-free conditions. In this report, a graphene-based electrolyte-gated field-effect transistor is developed as an immunosensor capable of sensitive analyte detection, even in the complex environment of physiological samples. The coimmobilization of an antibody fragment (F(ab′)2) and polyethylene glycol on the graphene surface allows for a highly sensitive and selective detection of a protein analyte, with a limit of detection in the low femtomolar range, both in high ionic strength buffer and undiluted serum. Multiparametric analysis of the device's analyte-dependent electronic response shows that the mechanism behind this very sensitive detection cannot be explained by a commonly reported electrostatic gating effect. Rather, the observed combination of charge neutrality point shifts and asymmetric mobility changes are attributed to the modulation of scattering by charged impurities, which seem to dominate the device's transfer characteristics. Furthermore, the reproducibility of the normalized signal response obtained from several different devices shows that this graphene-based immunosensor is capable of direct and quantitative measurements of protein analytes in untreated serum, imperative for diagnostic tools geared toward PoC applications.