Advances and Challenges in Integrated Circuits for Electrochemical Sensing: Enabling Next-Generation Biomedical and Molecular Applications

This manuscript provides a comprehensive review of the design, implementation, and advancements in integrated circuits (ICs) for electrochemical sensing, with a focus on biomedical and molecular applications. It begins by discussing the fundamental principles of electrochemical sensing and core modalities, including potentiometry, amperometry, impedimetry, and ISFET-based sensing, highlighting their unique requirements and challenges. A detailed analysis of state-of-the-art readout circuit architectures is presented, emphasizing strategies for achieving high dynamic range (DR), low noise, and enhanced stability while minimizing leakage currents. Both resistive and capacitive transimpedance amplifiers (TIAs) and current conveyor (CC)-based circuits are examined, exploring critical trade-offs between speed, power consumption, and noise performance. This review also discusses emerging applications such as DNA sequencing and molecular sensing, covering both ISFET and nanopore-based approaches, to showcase recent advancements in high-throughput, high-speed, and low-power interface circuit designs. By highlighting the challenges of the readout-circuit miniaturization, integration, and scalability, as well as the current limitations in existing approaches, this review provides a comprehensive synthesis of advancements in high-performance electrochemical readout architectures and their potential to address the evolving demands of modern biomedical applications.