One of the many applications of organ-on-a-chip (OOC) technology is the study of biological processes in human induced pluripotent stem cells (iPSCs) during pharmacological drug screening. It is of paramount importance to construct OOCs equipped with highly compact in situ sensors that can accurately monitor, in real time, the extracellular fluid environment and anticipate any vital physiological changes of the culture. In this paper, we report the co-fabrication of a CMOS smart sensor on the same substrate as our silicon-based OOC for real-time in situ temperature measurement of the cell culture. The proposed CMOS circuit is developed to provide the first monolithically integrated in situ smart temperature-sensing system on a micromachined silicon-based OOC device. Measurement results on wafer reveal a resolution of less than ±0.2 °C and a nonlinearity error of less than 0.05% across a temperature range from 30 to 40 °C. The sensor's time response is more than 10 times faster than the time constant of the convection-cooling mechanism found for a medium containing 0.4 ml of PBS solution. All in all, this work is the first step towards realizing OOCs with seamless integrated CMOS-based sensors capable to measure, in real time, multiple physical quantities found in cell culture experiments. It is expected that the use of commercial foundry CMOS processes may enable OOCs with very large scale of multi-sensing integration and actuation in a closed-loop system manner.

片上器官（OOC）技术的许多应用之一是在药理药物筛选过程中研究人诱导的多能干细胞（iPSC）中的生物学过程。构建配备有高度紧凑的原位传感器的OOC至关重要，该传感器可以实时准确地监测细胞外液环境并预测培养物中任何重要的生理变化。在本文中，我们报告了在与基于硅的OOC相同的基板上共同制造CMOS智能传感器的功能，用于细胞培养的实时原位温度测量。开发建议的CMOS电路以提供第一个单片原位集成微机械硅基OOC设备上的智能温度传感系统。晶圆上的测量结果表明，在30至40°C的温度范围内，分辨率小于±0.2°C，非线性误差小于0.05％。传感器的时间响应比包含0.4 ml PBS溶液的对流冷却机制的时间常数快10倍以上。总而言之，这项工作是通过无缝集成的基于CMOS的传感器实现OOC的第一步，该传感器能够实时测量细胞培养实验中发现的多个物理量。可以预期，使用商业代工厂CMOS工艺可以使OOC以闭环系统的方式实现非常大规模的多传感器集成和驱动。