A Verilog-A-Based Redox-Signal Transduction Model for Co-Simulating Surface-Bound Electrochemical Biosensors and Circuits.

Surface-bound electrochemical aptamer-based (E-AB) sensors are a promising approach for continuous in-vivo and in-vitro biomolecular monitoring because they offer high selectivity, sensitivity, and real-time detection. However, accurately co-simulating E-AB sensors with readout circuits remains challenging due to the redox reporter's position-dependent electron-transfer kinetics and the electrical double layer's (EDL) complex behavior at the electrode-electrolyte interface. Here, we present a compact, SPICE-compatible electrochemical cell model that combines a Verilog-A implementation of the Marcus-Hush-based electron-transfer (ET) kinetics with a fractional-order RC-ladder representation of the EDL's non-ideal capacitance. The conventional Butler-Volmer model is replaced by Marcus-Hush kinetics, which features bounded and quantum mechanically derived ET rate constants, improving not only the model's physical interpretability but also numerical stability in circuit simulations. The model was validated with two E-AB sensors using square-wave voltammetry (SWV) across a range of excitation frequencies and target concentrations to confirm that the simulated transient currents accurately capture ET kinetics, thermodynamics, and the Langmuir isotherm's concentration response. When co-simulated with a transimpedance amplifier constructed with the TI OPA4354, the model produced electronic noise spectra that more closely matched experimental data when compared with spectra simulated using the simplified Randles circuit model. These results demonstrate that the proposed model provides a physically grounded framework for simulating surface-bound redox-based electrochemical biosensors and enables accurate co-simulation with readout circuits.