High-throughput cell migration assay under combinatorial chemical environments by a novel 24-well-plate based device

Abstract

The quantitative studies of cell proliferation and migration under different chemical environments are important for both scientists and clinicians searching for new therapeutics. In this study, we developed a new device to pattern several types of cells in 24-well-plate and demonstrated its’ application in cancer cell proliferation and migration assay. The new device combined 3D-printed-silica-part for multi cell types loading with PDMS-through-hole-layer-part for cell micro-patterning which was matched with commercial 24-well-plate. This 24-well-plate based device is flexible and feasible in many applications and can be used in one piece or multi pieces. Besides the application for two types of cells proliferation and migration assay in one chemical condition, as a demonstration, the migration behaviors of four types of cells under 24 types of EGF + bFGF combinatorial conditions were studied. We believed this device could be widely used in clinical searching for new anti-cancer therapeutics and other related studies.

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References

  1. S. Cosson, M.P. Lutolf, Hydrogel microfluidics for the patterning of pluripotent stem cells. Sci. Rep. 4, 4462 (2014)

    Article  Google Scholar 

  2. P. Gheibi, K.J. Son, G. Stybayeva, A. Revzin, Harnessing endogenous signals from hepatocytes using a low volume multi-well plate. Integrative biology : quantitative biosciences from nano to macr 9, 427–435 (2017)

    Article  Google Scholar 

  3. Y.Y. Jun, K.Y. Hye, N. Kyuhwan, M.S. Yun, H.O. Kyung, P.D. Kyeong, et al., Hydrogel-incorporating unit in a well: 3D cell culture for high-throughput analysis. Lab Chip 18, 2604–2613 (2018)

    Article  Google Scholar 

  4. T.C. Kuo, C.T. Tan, Y.W. Chang, C.C. Hong, M.L. Kuo, Angiopoietin-like protein 1 suppresses slug to inhibit cancer cell motility. J. Clin. Invest. 123, 1082–1095 (2013)

    Article  Google Scholar 

  5. A. Kwon, H.L. Lee, K.M. Woo, et al., SMURF1 plays a role in EGF-induced breast cancer cell migration and invasion[J]. Mol. Cells 36(6), 548–555 (2013)

    Article  Google Scholar 

  6. T. Li, S. Jiang, Effect of bFGF on invasion of ovarian cancer cells through the regulation of Ets-1 and urokinase-type plasminogen activator[J]. Pharm. Biol. 48(2), 161–165 (2010)

    Article  Google Scholar 

  7. Z.J. Li, Q.X. Cai, X.Q. Zhang, G.W. Si, Q. Ouyang, C.X. Luo, Y.H. Tu, Barrier crossing in Escherichia coli Chemotaxis. Phys. Rev. Lett. 118, 098101 (2017)

    Article  Google Scholar 

  8. C.C. Liang, A.Y. Park, J.L. Guan, In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nat. Protoc. 2, 329–333 (2007)

    Article  Google Scholar 

  9. N.V. Menon, Y.J. Chuah, S. Phey, Y. Zhang, Y. Wu, V. Chan, et al., Microfluidic assay to study the combinatorial impact of substrate properties on mesenchymal stem cell migration. ACS Appl. Mater. Interfaces 7, 17095–17103 (2015)

    Article  Google Scholar 

  10. Q.H. Quan, S.W. Zhang, X.D. Wang, Q. Ouyang, Y.G. Wang, G. Yang, et al., A parallel and quantitative cell migration assay using a novel multi-well-based device. Biomed. Microdevices 18, 99 (2016)

    Article  Google Scholar 

  11. K.I. Saito, T. Oku, N. Ata, H. Miyashiro, M. Hattori, I. Saiki, A modified and convenient method for assessing tumor cell invasion and migration and its application to screening for inhibitors. Biol. Pharm. Bull. 20, 345–348 (1997)

    Article  Google Scholar 

  12. B. Shao, H.Y. Yuan, R. Zhang, X. Wang, S.W. Zhang, Q. Ouyang, et al., Reconstructing the regulatory circuit of cell fate determination in yeast mating response. PLoS Comput. Biol. 13, e1005671 (2017)

    Article  Google Scholar 

  13. C.H. Stuelten, C.A. Parent, D.J. Montell, Cell motility in cancer invasion and metastasis: Insights from simple model organisms. Nat. Rev. Cancer 18, 296–312 (2018)

    Article  Google Scholar 

  14. A. Valster, N.L. Tran, M. Nakada, M.E. Berens, A.Y. Chan, M. Symons, Cell migration and invasion assays. Methods 37, 208–215 (2005)

    Article  Google Scholar 

  15. Y. Wang, X. Tang, X. Feng, C. Liu, P. Chen, D. Chen, et al., A microfluidic digital single-cell assay for the evaluation of anticancer drugs. Anal. Bioanal. Chem. 407, 1139–1148 (2015)

    Article  Google Scholar 

  16. X. Yan, et al., bFGF promotes migration and induces cancer-associated fibroblasts differentiation of mouse bone mesenchymal stem cells to promote tumor growth. Stem Cells Dev. (2016). https://doi.org/10.1089/scd.2016.0217

  17. W. Yang, Z.J. Li, W.L. Zhang, C.X. Luo, Q. Ouyang, G. Yang, Y.G. Wang, A novel density control device for the study of cancer cell autocrine effect. Biomed. Microdevices 15, 683–689 (2013)

    Article  Google Scholar 

Download references

Acknowledgments

We would like to thank Yugang Wang, Qi Ouyang, Feng Liu for helpful discussions. This study was supported by the NSFC of China (11974002, 11674010) and the National Key Research and Development Project (SQ2018YFA090070-03).

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Correspondence to Gen Yang or Chunxiong Luo.

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Jian Xu and Xudong Wang are co-first authors.

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Xu, J., Wang, X., Li, X. et al. High-throughput cell migration assay under combinatorial chemical environments by a novel 24-well-plate based device. Biomed Microdevices 22, 40 (2020). https://doi.org/10.1007/s10544-020-00491-7

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Keywords

  • Migration assay
  • Cancer cells
  • Flexible devices
  • Scratch test
  • High-throughput screening