A 21952-Pixel Multi-Modal CMOS Cellular Sensor Array with 1568-Pixel Parallel Recording and 4-Point Impedance Sensing

A 21952-Pixel Multi-Modal CMOS Cellular Sensor Array with 1568-Pixel Parallel Recording and 4-Point Impedance Sensing
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具有 1568 像素并行记录和 4 点阻抗传感功能的 21952 像素多模式 CMOS 蜂窝传感器阵列

DOI:
10.23919/vlsic.2019.8778043
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发表时间:
2019
期刊:
2019 Symposium on VLSI Circuits
影响因子:
--
通讯作者:
Hua Wang
Hua Wang
中科院分区:
--
文献类型:
--
作者:
Doohwan Jung;Jong Seok Park;Gregory V. Junek;S. Grijalva;Sagar R. Kumashi;Adam Y. Wang;Sensen Li;H. Cho;Hua Wang

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本文提出了一种完全集成的 CMOS 多模态细胞传感器/刺激器阵列,具有 21952 个多模态像素、1568 个同步并行读出通道、单细胞分辨率为 16 μm×16 μm 像素间距和 3.6 mm×1.6 mm 组织级视场 (FoV),实现了高分辨率多参数细胞电位/阻抗/光学成像,用于整体细胞表征和基于细胞的分析。此外,该阵列系统报告了第一个具有 16 个并行阻抗传感通道的片上真正 4 点阻抗传感方案,可通过大幅缩放的电极和大电极-电解质界面阻抗实现精确的细胞阻抗测量。该芯片还支持并发 16 通道 5 位可重构电流模式细胞刺激。该芯片采用 130 nm 低成本标准 CMOS 工艺实现。成功测量了片上培养的新生大鼠心室肌细胞 (NRVM) 的细胞外电位 (700 μV-1.5 mV)。通过芯片上培养的心脏成纤维细胞,全芯片高分辨率光学图像和 4 点阻抗映射可以精确捕获细胞分布、生长、增殖和表面粘附。
This paper presents a fully integrated CMOS multi-modal cellular sensor/stimulator array with 21952 multi-modal pixels, 1568 simultaneous parallel readout channels, 16 μm×16 μm pixel pitch for single cell resolution, and 3.6 mm×1.6 mm tissue-level field-of-view (FoV), achieving high-resolution multi-parametric cellular potential/impedance/optical imaging for holistic cellular characterization and cell-based assays. Moreover, the array system reports the first on-chip true 4-point impedance sensing scheme with 16 parallel impedance sensing channels, which enables precise cellular impedance measurements with aggressively scaled electrodes and large electrode-electrolyte interfacial impedance. The chip also supports concurrent 16-channel 5-bit reconfigurable current-mode cell stimulation. The chip is implemented in a 130 nm low-cost standard CMOS process. Extracellular potentials (700 μV-1.5 mV) from on-chip cultured neonatal rat ventricular myocytes (NRVMs) are successfully measured. With on-chip cultured cardiac fibroblasts, full-chip high-resolution optical images and 4-point impedance mapping precisely capture cell distribution, growth, proliferation, and surface adhesion.