A Fast Electrochemical Impedance Spectroscopy with A Square Wave as Excitation Signal for Impedance-based Biomedical Applications.

This paper introduces a fast, high-accuracy methodology for conducting Electrochemical Impedance Spectroscopy (EIS) based on Fast Fourier Transform (FFT), to meet the requirements of portable, real-time biomedical impedance-based detections with Ultra-Microband (UMB) sensor. Instead of using white noise-like wideband signals as in conventional FFT-based EIS, the proposed method uses a square wave as the excitation signal, which achieves a fast, accurate EIS measurement, but no longer requires complex circuits like high-resolution DACs or frequency mixers for the signal generation. This work starts with the theoretical justification for treating the sensor as a Linear Time-Invariant (LTI), then the practical linear region for operating the sensor as an LTI system is experimentally verified and determined, which enables the capacity of employing the harmonics of a square wave for EIS measurements. A dynamic model of the charge-transfer resistance together with an approximated of the Constant Phase Element (CPE) are implemented with Verilog-A for simulations, and a circuit consisting of a control amplifier and a Trans-Impedance Amplifier (TIA) is designed and fabricated with 65 nm CMOS for validating its on-chip feasibility. This work shortens the EIS measurement time by 91.7% in a frequency sweep range from 0.5 Hz to 500 Hz, with only 2.73% average Mean Absolute Percentage Error (MAPE), compared to a commercial electrochemical instrument AutoLab, with five pre-modified electrodes across four different concentrations of Ferrocene Carboxylic Acid (FcCOOH), demonstrating this method is suitable for portable, real-time label-free EIS biomedical detections and applications.