Synergistic Distributed Thermal Regulation for On-CMOS High-Throughput Multimodal Amperometric DNA-Array Analysis

Accurate temperature regulation is critical for amperometric DNA analysis to achieve high fidelity, reliability, and throughput. In this work, a $9\times 6$ cell array of mixed-signal CMOS distributed temperature regulators for on-CMOS multimodal amperometric DNA analysis is presented. Three DNA analysis methods are supported, including constant potential amperometry (CPA), cyclic voltammetry (CV), and impedance spectroscopy (IS). In-cell heating and temperature-sensing elements are implemented in standard CMOS technology without post-processing. Using proportional–integral–derivative (PID) control, the local temperature can be regulated to within ±0.5 °C of any desired value between 20 °C and 90 °C. To allow the in-cell integration of independent PID control, a new mixed-signal design is proposed, where the two computationally intensive operations in the PID algorithm, multiplication and subtraction, are performed by an in-cell dual-slope multiplying ADC, resulting in a small area and low power consumption. Over 95% of the circuit blocks are synergistically shared among the four operating modes, including CPA, CV, IS, and the proposed temperature regulation mode. A 3 mm $\times3$ mm CMOS prototype fabricated in a 0.13- $\mu \text{m}$ CMOS technology has been fully experimentally characterized. The proposed distributed temperature regulation design and the mixed-signal PID implementation can be applied to a wide range of sensory and other applications.