A Ring-Oscillator-Based Graphene Platform for Kinetic Discrimination at the Inner Helmholtz Layer

Abstract

Graphene-based field-effect biosensors offer label-free detection of biomolecular binding, but sensitivity is fundamentally constrained by Debye screening at physiological ionic strength, and existing workarounds typically require bulky benchtop instrumentation such as impedance spectrometers. This paper proposes a fully electronic alternative: a differential ring oscillator in which graphene's quantum capacitance is placed in series with the Helmholtz and diffuse-layer capacitances of the sensing interface, converting interfacial capacitance dynamics directly into a continuously sampled oscillator frequency. Specific binding at the inner Helmholtz layer and bulk ionic screening proceed on very different timescales, and the platform discriminates between them from the time-domain shape of the frequency transient rather than its equilibrium value. A computational digital-twin framework, incorporating Langmuir binding kinetics and a combined shot/drift noise model, validated this principle on a synthetic dataset of specific-binding and bulk-screening events under 10-fold cross-validation. Rise time alone separates the two classes with 98.0% accuracy (AUC = 1.000), well ahead of the initial rate of frequency change considered on its own, while the complete feature set reaches 99.5% (SVM) and 99.3% (LDA) accuracy. These findings support timescale-resolved, frequency-domain readout as a route toward chip-scale, spectrometer-free biosensing, pending experimental validation on a fabricated device.