This article presents a fully integrated multi-modal CMOS cellular sensor/stimulator array chip with 21 952 pixels and 1568-pixel concurrent readouts, while each array pixel can be independently reconfigured to support three sensing and one stimulation modalities: cellular potential recording, optical-point impedance sensing, and bi-phasic current stimulation. The CMOS sensor/stimulator array chip provides 3.6 mm $\times $ 1.6 mm active field-of-view (FoV). Each pixel contains one 8 $\mu \text{m}\,\,\times $ 8 $\mu \text{m}$ gold deposited electrode, one 6 $\mu \text{m}\,\,\times $ 6 $\mu \text{m}$ photodiode, and in-pixel circuits within 8 $\mu \text{m}\,\,\times $ 11 $\mu \text{m}$ pixel area, while the pixel-to-pixel pitch is 16 $\mu \text{m}\,\,\times $ 16 $\mu \text{m}$ . As a proof of concept, the CMOS array is implemented in a standard 130-nm BiCMOS process. Comprehensive electrical testing (potential/optical/four-point impedance/stimulation) and biological measurements (potential/optical/four-point impedance) with on-chip rat cardiomyocytes demonstrate the functionalities and unique advantages of this multi-modality cellular array. With high throughput multi-modal cellular sensing supported at the pixel level, this array chip enables holistic characterization of on-chip cellular samples with single-cell resolution.

中文翻译：

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具有四点阻抗传感的 CMOS 21 952 像素多模式细胞生物传感器，用于整体细胞表征

本文介绍了一种完全集成的多模式 CMOS 蜂窝传感器/刺激器阵列芯片，具有 21 952 像素和 1568 像素并发读数，而每个阵列像素可以独立重新配置以支持三种传感和一种刺激模式：细胞电位记录、光学-点阻抗感应和双相电流刺激。CMOS 传感器/刺激器阵列芯片提供 3.6 mm $\times $ 1.6 毫米主动视场 (FoV)。每个像素包含一个 8 $\mu \text{m}\,\,\times $ 8 $\mu \text{m}$ 镀金电极，一个 6 $\mu \text{m}\,\,\times $ 6 $\mu \text{m}$ 光电二极管和 8 以内的像素内电路 $\mu \text{m}\,\,\times $ 11 $\mu \text{m}$ 像素面积，而像素到像素的间距为 16 $\mu \text{m}\,\,\times $ 16 $\mu \text{m}$ . 作为概念证明，CMOS 阵列采用标准 130 纳米 BiCMOS 工艺实现。使用片上大鼠心肌细胞进行的综合电气测试（电位/光学/四点阻抗/刺激）和生物测量（电位/光学/四点阻抗）证明了这种多模态细胞阵列的功能和独特优势。该阵列芯片支持像素级的高吞吐量多模态细胞传感，能够以单细胞分辨率对片上细胞样本进行整体表征。