We have previously demonstrated electrochemical circuits for measuring the concentration of various biomolecules and drugs using structure-switching aptamers. Structure-switching aptamers are single-stranded nucleic acids that can be sequenced to exhibit conformational changes when bound to specific biomolecules. By conjugating aptamers with a redox reporter, voltammetry or amperometry-based measurements can be applied and signals in the nano to pico-amp scale can be captured using transimpedance amplifiers (TIA). Because the signals of interest are very small, noise-cancellation techniques are required to minimize the noise produced by the first amplification stage, as it is typically the dominant noise source in cascaded amplifier chains. While the noise from individual amplifiers in the sensing front-end can be characterized, its impact on the closed-loop electrochemical circuit is challenging to quantify because of the parasitic electrical double-layer capacitor (EDLC) present at the TIA’s input terminal. The EDLC is a non-linear capacitance formed by the electrode’s charged surface and ions in the biofluid. Crucially, the EDLC introduces non-linear impedance and phase-shifts that impact subsequent signals in the cascaded amplifier chain. In this work, we propose a mixed-signal noise-cancellation technique to reduce the noise contributed by the amplification chain’s first stage TIA.
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