Shi Yimin, Sun Sheng, Liu Hui, Zhao Mingda, Qin Meiyan, Liu Jinlong, Hu Jingfang, Zhao Yang, Li Mingxiao, Zhang Lingqian, Huang Chengjun
Institute of Microelectronics of the Chinese Academy of Sciences, Beijing 100029, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Lab Chip. 2025 Jan 14;25(2):253-262. doi: 10.1039/d4lc00817k.
Transepithelial electrical resistance (TEER) measurement is a label free, rapid and real-time technique, which is commonly used to evaluate the integrity of cell barriers. TEER characterization is important for applications, such as tissue (brain, intestines, lungs) barrier modeling, drug screening, and cell growth monitoring. Traditional TEER methods usually only show the average impedance of the whole cell layer, and lack accuracy and the characterization of internal spatial differences within cell layer regions. Here, we introduce a new spatial TEER strategy that utilizes microelectrode arrays (MEA) integrated in a Transwell to dynamically monitor TEER. A new electrical model which could reveal spatial impedance non-uniformity was proposed to extract accurate resistance from the measured data. Based on our method, the TEER signals from 16 different regions were successfully monitored in real time. The mapped impedance hotspots in different regions closely correlate with both fluorescence cell staining signals and calculated cell coverage, indicating the effectiveness of the developed spatial TEER system in monitoring local cell growth . The real-time spatial TEER responses to ethylene glycol-bis(β-aminoethylether)-,,','-tetraacetic acid (EGTA) and cisplatin were studied, which could either reduce barrier integrity or inhibit cellular growth. The obtained results demonstrated the spatial TEER's applicability for cell barrier function and cell growth monitoring. Our approach provides accurate spatial electrical information of cell barriers and holds potential applications in drug development and screening.
跨上皮电阻（TEER）测量是一种无标记、快速且实时的技术，常用于评估细胞屏障的完整性。TEER表征对于诸如组织（脑、肠、肺）屏障建模、药物筛选和细胞生长监测等应用非常重要。传统的TEER方法通常仅显示整个细胞层的平均阻抗，缺乏准确性以及对细胞层区域内内部空间差异的表征。在此，我们介绍一种新的空间TEER策略，该策略利用集成在Transwell中的微电极阵列（MEA）来动态监测TEER。提出了一种能够揭示空间阻抗不均匀性的新电模型，以便从测量数据中提取准确的电阻。基于我们的方法，成功实时监测了来自16个不同区域的TEER信号。不同区域映射的阻抗热点与荧光细胞染色信号和计算出的细胞覆盖率密切相关，表明所开发的空间TEER系统在监测局部细胞生长方面的有效性。研究了对乙二醇双（β - 氨基乙醚） - N,N,N',N'-四乙酸（EGTA）和顺铂的实时空间TEER响应，它们均可降低屏障完整性或抑制细胞生长。获得的结果证明了空间TEER在细胞屏障功能和细胞生长监测方面的适用性。我们的方法提供了细胞屏障准确的空间电信息，并在药物开发和筛选中具有潜在应用。
