Graphene Electric Double-Layer Transistors for Enhanced-Sensitivity Label-Free Detection of Human Serum Albumin
Accurate detection of human serum albumin (HSA) is essential for the early diagnosis and monitoring of renal and hepatic disorders. We present a graphene-based electrolyte-gated field-effect transistor (EGFET) for label-free, real-time quantification of HSA under non-Faradaic operation. Devices exploit the high interfacial capacitance of the electric double layer (EDL) to transduce electrostatic perturbations induced by albumin adsorption into measurable conductance modulation. Negatively charged HSA molecules induce systematic modulation of the graphene channel, producing a concentration-dependent displacement of the Dirac voltage consistent with p-type doping. To establish a molecular-level interpretation of the sensing response, Brownian Dynamics simulations show that HSA adsorbs onto graphene through multiple adsorption orientations associated with heterogeneous interfacial charge distributions and variable dipole alignments relative to the surface. Adsorption is energetically stabilized by van der Waals interactions. Analysis of transfer characteristics across concentrations ranging from 0.01 to 30mgmL-1 reveals a correlation between surface charge density and carrier transport modulation within the electric double layer. Optimized devices exhibit a limit of detection of 0.0087 mg mL-1 and a linear dynamic range extending to 10 mg mL-1. The response remains non-Faradaic under sub-volt operation with reversible and reproducible behavior. The use of an inverse-mobility analytical metric highlights the role of disorder-enhanced carrier scattering in signal amplification, enabling sensitive electrostatic detection while preserving reversible device operation. These results establish liquid-gated graphene EGFETs as a promising platform for quantitative protein sensing and provide insight into disorder-mediated transport mechanisms in graphene bioelectronic devices.