IEEE Trans Biomed Circuits Syst. 2020 Jun;14(3):477-489. doi: 10.1109/TBCAS.2020.2978000. Epub 2020 Mar 3.
This paper presents a 32 × 32 ISFET array with in-pixel dual-sensing and programmability targeted for on-chip DNA amplification detection. The pixel architecture provides thermal and chemical sensing by encoding temperature and ion activity in a single output PWM, modulating its frequency and its duty cycle respectively. Each pixel is composed of an ISFET-based differential linear OTA and a 2-stage sawtooth oscillator. The operating point and characteristic response of the pixel can be programmed, enabling trapped charge compensation and enhancing the versatility and adaptability of the architecture. Fabricated in 0.18 μm standard CMOS process, the system demonstrates a quadratic thermal response and a highly linear pH sensitivity, with a trapped charge compensation scheme able to calibrate 99.5% of the pixels in the target range, achieving a homogeneous response across the array. Furthermore, the sensing scheme is robust against process variations and can operate under various supply conditions. Finally, the architecture suitability for on-chip DNA amplification detection is proven by performing Loop-mediated Isothermal Amplification (LAMP) of phage lambda DNA, obtaining a time-to-positive of 7.71 minutes with results comparable to commercial qPCR instruments. This architecture represents the first in-pixel dual thermo-chemical sensing in ISFET arrays for Lab-on-a-Chip diagnostics.
本文提出了一种 32×32 的 ISFET 阵列，具有像素内双传感和可编程性，旨在用于片上 DNA 扩增检测。该像素结构通过在单个输出 PWM 中对温度和离子活度进行编码，分别调制其频率和占空比，从而提供热和化学传感。每个像素由基于 ISFET 的差分线性 OTA 和两级锯齿波振荡器组成。像素的工作点和特性响应可以编程，从而实现俘获电荷补偿，增强架构的多功能性和适应性。该系统采用 0.18μm 标准 CMOS 工艺制造，展示了二次热响应和高度线性的 pH 灵敏度，采用俘获电荷补偿方案能够校准目标范围内 99.5%的像素，实现了阵列的均匀响应。此外，该传感方案对工艺变化具有鲁棒性，可以在各种电源条件下工作。最后，通过对噬菌体 lambda DNA 的环介导等温扩增 (LAMP) 进行证明了该架构在片上 DNA 扩增检测中的适用性，获得了 7.71 分钟的阳性时间，结果可与商业 qPCR 仪器相媲美。该架构代表了用于片上诊断的 ISFET 阵列中首次实现的像素内双热-化学传感。
