4.7 Article

3D microgroove electrical impedance sensing to examine 3D cell cultures for antineoplastic drug assessment

Journal

MICROSYSTEMS & NANOENGINEERING
Volume 6, Issue 1, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41378-020-0130-x

Keywords

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Funding

  1. National Natural Science Foundation of China [81811530116, 31800826, 61901412]
  2. Fundamental Research Funds for the Central Universities [2018QNA5018, 2018FZA5018]

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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. Medical sensors: 3D cancer cell analysisA new micro groove impedance sensor enables the real-time and high-throughput analysis of 3D lung cancer cell models. In-vitro cell-based assays are important for the screening of new cancer drugs. However, many drug screening approaches only work for 2D arrangements of cells, yet it is known that 3D arrangements can behave very differently. Electrochemical impedance spectroscopy is widely used for monitoring the behavior of 2D arrangements of cells, yet attempts to extend it to 3D are limited. Now, a team led by Ping Wang from Zhejiang University demonstrate a micro groove impedance sensor for drug screening of 3D cancer cell models. Substantial differences were seen compared to 2D analysis, demonstrating the importance of tools for assessing 3D cancer models in drug development.

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