Modern biosensors play a critical role in healthcare and have a quickly growing commercial market. Compared to traditional optical-based sensing, electrochemical biosensors are attractive due to superior performance in response time, cost, complexity and potential for miniaturization. To address the shortcomings of traditional benchtop electrochemical instruments, in recent years, many complementary metal oxide semiconductor (CMOS) instrumentation circuits have been reported for electrochemical biosensors. This paper provides a review and analysis of CMOS electrochemical instrumentation circuits. First, important concepts in electrochemical sensing are presented from an instrumentation point of view. Then, electrochemical instrumentation circuits are organized into functional classes, and reported CMOS circuits are reviewed and analyzed to illuminate design options and performance tradeoffs. Finally, recent trends and challenges toward on-CMOS sensor integration that could enable highly miniaturized electrochemical biosensor microsystems are discussed. The information in the paper can guide next generation electrochemical sensor design.

High-density on-chip electrochemical biosensor arrays are advancing toward a crucial role in health monitoring and development of new medicines and medical treatments. Nanopore and ion channel based sensors especially have great potential but present demanding resolution/speed/power/area requirements on instrumentation circuits. This paper presents a pixel-level current readout circuit and new group-cluster architecture to address the circuit challenges in high-performance biosensor arrays. Fabricated in 0.5 μm CMOS, this electrochemical voltammetry circuit achieves 7.2 pArms noise in an 11.5-kHz bandwidth and only consumes 21-μ W power and 0.06 mm ² area per readout channel. Cyclic voltammetry experiments in a potassium ferricyanide solution and patch-clamp whole-cell experiments were performed to validate the circuit's feasibility for electrochemical biosensor applications.

Chronoamperometric gas sensor arrays show great promise for ultra-low power consumption and low cost for wearable gas sensing devices for human safety and health monitoring. This paper presents a novel power efficient instrumentation circuit with high sensitivity and large dynamic range for wearable chronoamperometric gas sensor arrays. This instrumentation combines an input digital modulation technique and a semi-synchronous incremental ΣΔ ADC structure to achieve very high power efficiency over a large dynamic range with high sensitivity. The proposed instrumentation was implemented in 0.5 μm CMOS technology. Measurement results demonstrate that 164dB cross-scale dynamic range and 100 fA sensitivity are achieved with a high power efficiency.