A novel micro-groove impedance sensor for 3D cell viability monitoring and high-throughput drug screening

Yuxiang Pan, Yonglian Qiu, Deming Jiang, Xin Liu, Chenlei Gu, H. Wan, Ping Wang
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Abstract

Drug screening is traditionally based on the pharmacodynamic models from 2D cell culture or animal experiments. Recently, three-dimensional (3D) tumor cell models have attracted increasing interest due to their great advantages in simulating more accurately the heterogeneous tumor behavior in vivo. Drug screening based on 3D cells can provide more accurate efficacy results. However, it is difficult to realize real-time and label-free monitoring of 3D cell viability by common imaging techniques. To solve this technical difficulty, a novel micro-groove impedance sensor (MGIS) was specially developed for 3D cell viability real-time monitoring. Precultured 3D spheroids cells are trapped in the micro-cavity with opposite gold electrodes for the in-situ impedance measurement. The presence of 3D spheroid cells will lead to the change of electron transfer efficiency on the electrode surface, which will lead to the change of impedance. When antitumor drugs act on the spheroid cells, the spheroids will cleave and the impedance will decrease. In order to verify the accuracy of MGIS chip, we adopted standard live/dead fluorescence staining to validate the activity of 3D cells. Furthermore, anti-tumor drug sensitivity tests were conducted to validate the drug screening ability of MGIS plat-form. All the results demonstrate that the MGIS is able to monitoring 3D cell viability and drug screening.
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一种用于三维细胞活力监测和高通量药物筛选的新型微槽阻抗传感器
药物筛选传统上是基于二维细胞培养或动物实验的药效学模型。近年来,三维(3D)肿瘤细胞模型因其在更准确地模拟体内异质性肿瘤行为方面的巨大优势而引起了越来越多的关注。基于3D细胞的药物筛选可以提供更准确的疗效结果。然而,常规成像技术难以实现对三维细胞活力的实时、无标记监测。为了解决这一技术难题,研制了一种新型的微槽阻抗传感器(MGIS),用于三维细胞活力实时监测。预培养的三维球体细胞被捕获在具有相对金电极的微腔中,用于原位阻抗测量。三维球体电池的存在会导致电极表面电子传递效率的变化,从而导致阻抗的变化。当抗肿瘤药物作用于球状细胞时,球状细胞分裂,阻抗降低。为了验证MGIS芯片的准确性,我们采用标准的活/死荧光染色来验证3D细胞的活性。通过抗肿瘤药敏试验验证MGIS平台的药物筛选能力。所有结果表明,MGIS能够监测三维细胞活力和药物筛选。
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