Electrochemical live monitoring of tumor cell migration out of micro-tumors on an innovative multiwell high-dense microelectrode array
Electrochemical live monitoring of tumor cell migration out of micro-tumors on an innovative multiwell high-dense microelectrode array
复制标题
DOI：
10.1038/s41598-019-50326-6
复制
发表时间：
2019-09-25
影响因子：
4.6
通讯作者：
Robitzki, Andrea A.
中科院分区：
文献类型：
--
作者：
Jahnke, Heinz-Georg;Mewes, Agneta;Robitzki, Andrea A.
了解细胞在肿瘤组织外的迁移和扩散对于研究肿瘤恶性和转移的机制和原因具有重要意义。尽管已经有了研究单层细胞培养上细胞迁移的方法，如Transwell分析，但监测细胞从3D有机物或肿瘤组织样本中扩散的新技术是非常必要的。在此背景下，我们开发了一种创新的高密度微电极阵列，用于阻抗监测来自3D肿瘤培养的细胞迁移。作为概念的验证，一个强迁移的乳腺癌细胞系(MDA-MB-231)和两个恶性黑色素瘤细胞系(T30.6.9，T12.8.10ZII)被用于建立存活的微肿瘤模型。迁移倾向通过144小时的阻抗监测来确定，通过显微镜进行关联，并通过Transwell分析进行验证。复盖电极的阻抗分析和相对阻抗最大值揭示了有关增殖效应贡献的更多信息。更引人注目的是，使用丝裂霉素C的参考群体处理增殖受到抑制的球体，可以区分增殖和迁移。因此，我们基于高密度微电极阵列的阻抗迁移监测具有自动化定量分析系统的能力，该系统可以轻松扩大规模并集成到芯片设备实验室中。
Understanding of cell migration and spreading out of tumor tissue is of great interest concerning the mechanism and causes of tumor malignancy and metastases. Although there are methods available for studying cell migration on monolayer cell cultures like transwell assays, novel techniques for monitoring cell spreading out of 3D organoids or tumor tissue samples are highly required. In this context, we developed an innovative high-dense microelectrode array for impedimetric monitoring of cell migration from 3D tumor cultures. For a proof of concept, a strongly migrating breast cancer cell line (MDA-MB-231) and two malignant melanoma cell lines (T30.6.9, T12.8.10ZII) were used for generating viable micro-tumor models. The migration propensity was determined by impedimetric monitoring over 144 hours, correlated by microscopy and validated by transwell assays. The impedimetric analysis of covered electrodes and the relative impedance maximum values revealed extended information regarding the contribution of proliferative effects. More strikingly, using reference populations of mitomycin C treated spheroids where proliferation was suppressed, distinction of proliferation and migration was possible. Therefore, our high-dense microelectrode array based impedimetric migration monitoring has the capability for an automated quantitative analysis system that can be easily scaled up as well as integrated in lab on chip devices.