A CMOS 21 952-Pixel Multi-Modal Cell-Based Biosensor With Four-Point Impedance Sensing for Holistic Cellular Characterization
A CMOS 21 952-Pixel Multi-Modal Cell-Based Biosensor With Four-Point Impedance Sensing for Holistic Cellular Characterization
复制标题
具有四点阻抗传感功能的 CMOS 21 952 像素多模式细胞生物传感器，用于全面细胞表征
DOI：
10.1109/jssc.2021.3085571
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发表时间：
2021
影响因子：
5.4
通讯作者：
Hua Wang
中科院分区：
文献类型：
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作者：
Doohwan Jung;Gregory V. Junek;Jong Seok Park;Sagar R. Kumashi;Adam Y. Wang;Sensen Li;S. Grijalva;Natasha Fernandez;H. Cho;Hua Wang
本文介绍了一种完全集成的多模式CMOS细胞传感器/刺激器阵列芯片，具有21 952个像素和1568个像素的并发读出，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、光点阻抗传感和两相电流刺激。该cmos传感器/刺激器阵列芯片提供3.6 mm；直插式公式=“LaTeX”；$\x$\x；/特式公式1.6 mm有效视场(FOV)。每个像素包含一个8<；内联公式=“LaTeX”&>；$\MU\Text{m}\，\，\次$<；/内联-公式；8<；内联-公式=“LaTeX”>；$\MU\Text{m}$<；/内联-公式>；镀金电极，一个；INLINE-FORMULE；<；TEX-MATH NOTATION=“LaTeX”>；$\MU\Text{m}\，\，\Times$<；/Tex-FORMIC>；6<；INLINE-FORMUMAL>；<；Tex-Math NOTATION=“LaTeX”>；$\mU\Text{m}$<；/Tex-MASH>；；<；/INLINE-FORMULA>；光电二极管和像素内电路纹理数学符号=“LaTeX”>；$\MU\Text{m}\，\，\次$<；/Tex-Math&>；/inline-FORMULA>；11<；inline-FORMULA&><；文本数学符号=“LaTeX”>；$\MU\Text{m}$<；/Tex-FORMAX&>；/行内公式；像素区域，而像素到像素的间距为16；行内公式；Tex-ath notation=“LaTeX”>；$\MU\Text{m}\，\，\Times$<；/Tex-Math&>；<；/INLINE-FORMULA>；16<；INLINE-FORMULA>；<；TEX-MATH NOTATION=“LaTeX”>；$\MU\Text{m}$<；/Tex-MASH&>；<；/Inline-FORMULE>；。作为概念验证，该CMOS阵列是在标准的130 nm BiCMOS工艺中实现的。芯片上大鼠心肌细胞的全面电学测试(电位/光学/四点阻抗/刺激)和生物学测量(电位/光学/四点阻抗)展示了这种多模式细胞阵列的功能和独特优势。这种阵列芯片支持像素级别的高通量多模式细胞传感，能够以单细胞分辨率对芯片上的细胞样本进行整体表征。
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 <inline-formula> <tex-math notation="LaTeX">$\times $ </tex-math></inline-formula> 1.6 mm active field-of-view (FoV). Each pixel contains one 8 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}\,\,\times $ </tex-math></inline-formula> 8 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> gold deposited electrode, one 6 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}\,\,\times $ </tex-math></inline-formula> 6 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> photodiode, and in-pixel circuits within 8 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}\,\,\times $ </tex-math></inline-formula> 11 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> pixel area, while the pixel-to-pixel pitch is 16 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}\,\,\times $ </tex-math></inline-formula> 16 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula>. 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.