In recent decades, three-dimensional (3D) cancer cell models have attracted increasing interest in the field of drug screening due to their significant advantages in more accurate simulations of heterogeneous tumor behavior in vivo compared to two-dimensional models. Furthermore, drug sensitivity testing based on 3D cancer cell models can provide more reliable in vivo efficacy prediction. The gold standard fluorescence staining is hard to achieve real-time and label-free viability monitoring in 3D cancer cell models. In this study, a microgroove impedance sensor (MGIS) was specially developed for the dynamic and noninvasive monitoring of 3D cell viability. 3D cancer cells were trapped in microgrooves with gold electrodes on opposite walls for in situ impedance measurement. The change in the number of live cells caused inversely proportional changes to the impedance magnitude of the entire cell/Matrigel construct and reflected the proliferation and apoptosis of the 3D cells. It was confirmed that the 3D cell viability detected by the MGIS was highly consistent with the standard live/dead staining by confocal microscope characterization. Furthermore, the accuracy of the MGIS was validated quantitatively using a 3D lung cancer model and sophisticated drug sensitivity testing. In addition, the parameters of the MGIS in the measurement experiments were optimized in detail using simulations and experimental validation. The results demonstrated that the MGIS coupled with 3D cell culture would be a promising platform to improve the efficiency and accuracy of cell-based anticancer drug screening in vitro.

近几十年来，由于与二维模型相比，三维 (3D) 癌细胞模型在更准确地模拟体内异质肿瘤行为方面具有显着优势，因此在药物筛选领域引起了越来越多的兴趣。此外，基于 3D 癌细胞模型的药物敏感性测试可以提供更可靠的体内疗效预测。金标准荧光染色很难在 3D 癌细胞模型中实现实时和无标记的生存能力监测。在这项研究中，专门开发了一种微槽阻抗传感器 (MGIS)，用于动态和无创监测 3D 细胞活力。3D 癌细胞被困在微槽中，相对壁上有金电极，用于原位阻抗测量。活细胞数量的变化导致整个细胞/基质胶构建体的阻抗大小成反比变化，并反映了 3D 细胞的增殖和凋亡。经共聚焦显微镜表征证实，MGIS 检测到的 3D 细胞活力与标准活/死染色高度一致。此外，使用 3D 肺癌模型和复杂的药物敏感性测试对 MGIS 的准确性进行了定量验证。此外，MGIS在测量实验中的参数通过模拟和实验验证进行了详细优化。结果表明，MGIS 与 3D 细胞培养相结合，将成为提高体外细胞抗癌药物筛选效率和准确性的有前途的平台。