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Bionic 3D spheroids biosensor chips for high-throughput and dynamic drug screening

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Abstract

To perform the drug screening, planar cultured cell models are commonly applied to test efficacy and toxicity of drugs. However, planar cultured cells are different from the human 3D organs or tissues in vivo. To simulate the human 3D organs or tissues, 3D spheroids are developed by culturing a small aggregate of cells which reside around the extracellular matrix and interact with other cells in liquid media. Here we apply lung carcinoma cell lines to engineer the 3D lung cancer spheroid-based biosensor using the interdigitated electrodes for drug efficacy evaluation. The results show 3D spheroid had higher drug resistance than the planar cell model. The anticarcinogen inhibition on different 3D lung cancer spheroid models (A549, H1299, H460) can be quantitatively evaluated by electric impedance sensing. Besides, we delivered combination of anticarcinogens treatments to A549 spheroids which is commonly used in clinic treatment, and found the synergistic effect of cisplatin plus etoposide had higher drug response. To simultaneously test the drug efficacy and side effects on multi-organ model with circulatory system, a connected multiwell interdigitated electrode arraywas applied to culture different organoid spheroids. Overall, the organization of 3D cancer spheroids-based biosensor, which has higher predictive value for drug discovery and personalized medicine screening, is expected to be well applied in the area of pharmacy and clinical medicine.

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Acknowledgements

This work was supported by National Natural Science Fund of China (No. 61320106002, 31627801, 31661143030) and National 973 project (No. 2015CB352101).

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Authors and Affiliations

  1. Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027, China

    Qian Wu, Xinwei Wei, Yuxiang Pan, Yingchang Zou, Ning Hu & Ping Wang

  2. State Key Laboratory of Transducer Technology, Chinese Academy of Sciences, Shanghai, 200050, China

    Qian Wu, Ning Hu & Ping Wang

Authors
  1. Qian Wu
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  2. Xinwei Wei
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  3. Yuxiang Pan
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  4. Yingchang Zou
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  5. Ning Hu
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  6. Ping Wang
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Corresponding authors

Correspondence to Ning Hu or Ping Wang.

Electronic supplementary material

ESM 1

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Fig. S1 Long term culture of A549 spheroid form 1 to 5 days (a-e), cells assembled more closely and the surface became smooth. f. Live/dead staining of A549 spheroid. This fluorescent merged images present high viability of spheroid in day 5. Scale bar 300 μm.

ESM 2

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Fig. S2 Determination of cells number for 2D culture control. A group of representative cell growth curves of A549 (a) and H1299 (b) cells at different cell numbers ranging from 1250 to 20000 cells/well. The linear relationship of A549 (c) and H1299 (d) cells between the cell number and the CI value at 12h after cells were seeded.

ESM 3

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Fig. S3 Cisplatin, etoposide and pemetrexed with the concentration of 10 μM, 10 μM and 100 μM, respectively, were used to detect the impedance for 12h as well as the medium control. All anticancirogens were diluted by standard medium as they treat to spheroids.

ESM 4

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Fig. S4 a. The multi-organs-on-a-chip platform linked through silicone tube and cycled byperistaltic pump. b. Fluid with drug traversed to drug well, HL-1, A549 and HepG2 successively.

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Wu, Q., Wei, X., Pan, Y. et al. Bionic 3D spheroids biosensor chips for high-throughput and dynamic drug screening. Biomed Microdevices 20, 82 (2018). https://doi.org/10.1007/s10544-018-0329-x

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  • DOI: https://doi.org/10.1007/s10544-018-0329-x

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