IEEE Trans Biomed Circuits Syst. 2018 Feb;12(1):80-94. doi: 10.1109/TBCAS.2017.2759220.
This paper presents a fully integrated CMOS multimodality joint sensor/stimulator array with 1024 pixels for real-time holistic cellular characterization and drug screening. The proposed system consists of four pixel groups and four parallel signal-conditioning blocks. Every pixel group contains 16 × 16 pixels, and each pixel includes one gold-plated electrode, four photodiodes, and in-pixel circuits, within a pixel footprint. Each pixel supports real-time extracellular potential recording, optical detection, charge-balanced biphasic current stimulation, and cellular impedance measurement for the same cellular sample. The proposed system is fabricated in a standard 130-nm CMOS process. Rat cardiomyocytes are successfully cultured on-chip. Measured high-resolution optical opacity images, extracellular potential recordings, biphasic current stimulations, and cellular impedance images demonstrate the unique advantages of the system for holistic cell characterization and drug screening. Furthermore, this paper demonstrates the use of optical detection on the on-chip cultured cardiomyocytes to real-time track their cyclic beating pattern and beating rate.
本文提出了一种完全集成的 CMOS 多模态联合传感器/刺激器阵列,具有 1024 个像素,可用于实时整体细胞特征化和药物筛选。该系统由四个像素组和四个并行信号处理模块组成。每个像素组包含 16×16 个像素,每个像素包括一个镀金电极、四个光电二极管和像素内电路,位于一个像素足迹内。每个像素支持实时细胞外电势记录、光检测、电荷平衡双相电流刺激和细胞阻抗测量,用于同一细胞样本。该系统采用标准的 130nm CMOS 工艺制造。大鼠心肌细胞成功在芯片上培养。测量的高分辨率光学不透明度图像、细胞外电势记录、双相电流刺激和细胞阻抗图像证明了该系统在整体细胞特征化和药物筛选方面的独特优势。此外,本文还展示了在芯片上培养的心肌细胞上使用光学检测实时跟踪其周期性跳动模式和跳动率。