Multi-parametric functional imaging of cell cultures and tissues with a CMOS microelectrode array.
Multi-parametric functional imaging of cell cultures and tissues with a CMOS microelectrode array.
复制标题
用CMOS微电极阵列对细胞培养物和组织进行多参数功能成像。
DOI：
10.1039/d1lc00878a
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发表时间：
2022-03-29
期刊：
影响因子：
6.1
通讯作者：
Park H
中科院分区：
文献类型：
--
作者：
Abbott J;Mukherjee A;Wu W;Ye T;Jung HS;Cheung KM;Gertner RS;Basan M;Ham D;Park H
基于电极的阻抗和电化学测量可以提供使用光学显微镜技术难以获得的细胞生物学信息。这种电学方法是非侵入性、无标签和连续的，消除了对荧光记者的需要，并克服了光学成像的吞吐量/时间分辨率限制。尽管如此，基于电极的技术还没有得到广泛的应用，因为设备通常每口井包含的电极很少，导致总读数有噪声。互补金属氧化物半导体微电极阵列(MEA)有时被用于亚细胞间距的每孔数千个电极的电生理测量，但在电生理学之外只执行细胞附着的基本阻抗映射。在这里，我们报告了新的场基阻抗映射和电化学映射/图案化技术，以扩大CMOS-MEA细胞生物学的应用。该方法能够以单细胞空间分辨率(20μm电极间距)准确测量细胞附着、生长/伤口愈合、细胞-细胞黏附、代谢状态和氧化还原特性。这些测量可以量化表达癌基因的细胞与野生型对照细胞的粘附性和新陈代谢差异。芯片规模集成设备捕获的多参数、细胞数量统计数据为全电子高通量活细胞分析开辟了新的途径，用于表型筛选和药物发现应用。一种结合了新的阻抗和电化学技术的CMOS-MEA器件，用于测量细胞附着、生长/伤口愈合、细胞-细胞黏附、代谢状态和氧化还原特性，具有单细胞空间分辨率，适用于细胞生物学应用。
Electrode-based impedance and electrochemical measurements can provide cell-biology information that is difficult to obtain using optical-microscopy techniques. Such electrical methods are non-invasive, label-free, and continuous, eliminating the need for fluorescence reporters and overcoming optical imaging's throughput/temporal resolution limitations. Nonetheless, electrode-based techniques have not been heavily employed because devices typically contain few electrodes per well, resulting in noisy aggregate readouts. Complementary metal-oxide-semiconductor (CMOS) microelectrode arrays (MEAs) have sometimes been used for electrophysiological measurements with thousands of electrodes per well at sub-cellular pitches, but only basic impedance mappings of cell attachment have been performed outside of electrophysiology. Here, we report on new field-based impedance mapping and electrochemical mapping/patterning techniques to expand CMOS-MEA cell-biology applications. The methods enable accurate measurement of cell attachment, growth/wound healing, cell–cell adhesion, metabolic state, and redox properties with single-cell spatial resolution (20 μm electrode pitch). These measurements allow the quantification of adhesion and metabolic differences of cells expressing oncogenes versus wild-type controls. The multi-parametric, cell-population statistics captured by the chip-scale integrated device opens up new avenues for fully electronic high-throughput live-cell assays for phenotypic screening and drug discovery applications. A CMOS-MEA device combined with new impedance and electrochemical techniques measures cell attachment, growth/wound healing, cell–cell adhesion, metabolic state, and redox properties with single-cell spatial resolution for cell-biology applications.