Three-dimensional (3D) cell culture has developed rapidly over the past 5-10 years with the goal of better replicating human physiology and tissue complexity in the laboratory. Quantifying cellular responses is fundamental in understanding how cells and tissues respond during their growth cycle and in response to external stimuli. There is a need to develop and validate tools that can give insight into cell number, viability, and distribution in real-time, nondestructively and without the use of stains or other labelling processes. Impedance spectroscopy can address all of these challenges and is currently used both commercially and in academic laboratories to measure cellular processes in 2D cell culture systems. However, its use in 3D cultures is not straight forward due to the complexity of the electrical circuit model of 3D tissues. In addition, there are challenges in the design and integration of electrodes within 3D cell culture systems. Researchers have used a range of strategies to implement impedance spectroscopy in 3D systems. This review examines electrode design, integration, and outcomes of a range of impedance spectroscopy studies and multiparametric systems relevant to 3D cell cultures. While these systems provide whole culture data, impedance tomography approaches have shown how this technique can be used to achieve spatial resolution. This review demonstrates how impedance spectroscopy and tomography can be used to provide real-time sensing in 3D cell cultures, but challenges remain in integrating electrodes without affecting cell culture functionality. If these challenges can be addressed and more realistic electrical models for 3D tissues developed, the implementation of impedance-based systems will be able to provide real-time, quantitative tracking of 3D cell culture systems.

中文翻译：

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三维（3D）细胞培养监控：阻抗谱的机遇与挑战。

三维（3D）细胞培养在过去5到10年间发展迅速，其目标是在实验室中更好地复制人体生理和组织复杂性。量化细胞反应是了解细胞和组织在其生长周期中如何反应以及对外部刺激反应的基础。需要开发和验证工具，这些工具可以实时，无损地洞察细胞数量，存活力和分布，而无需使用染色剂或其他标记过程。阻抗光谱法可以解决所有这些挑战，目前已在商业和学术实验室中用于测量2D细胞培养系统中的细胞过程。然而，由于3D组织的电路模型的复杂性，其在3D培养物中的使用不是直接的。此外，在3D细胞培养系统中电极的设计和集成方面也存在挑战。研究人员已使用多种策略在3D系统中实施阻抗谱。这篇综述检查了与3D细胞培养相关的一系列阻抗谱研究和多参数系统的电极设计，集成和结果。尽管这些系统提供了完整的培养数据，但阻抗层析成像方法已显示出如何使用此技术来实现空间分辨率。这篇综述展示了如何使用阻抗谱和层析成像技术在3D细胞培养中提供实时感测，但是在不影响细胞培养功能的前提下集成电极仍然存在挑战。如果可以解决这些挑战，并为3D组织开发出更逼真的电子模型，