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A novel three-dimensional microfluidic platform for on chip multicellular tumor spheroid formation and culture

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Abstract

The formation of three-dimensional (3D) multicellular cell spheroids such as microspheres and embryoid bodies has recently gained much attention as a useful cell culture technique, but few studies have investigated the suitability of glass for spheroids formation and culture. In this work, we present a novel three-dimensional microfluidic device made of poly(dimethylsiloxane) (PDMS) and glass for the easy and rapid synthesis and culture of tumor spheroid. The cell culture unit is composed of an array of microwells on the bottom of a glass plate, bigger microwells and elastomeric microchannels on the top of a PDMS plate. Cell suspension can be easily introduced into the cell culture unit and exchange with the external liquid environment by the microfluidic channels. A single tumor spheroid can be formed and cultured in each glass cell culture chamber, the surface of which was modified with poly(vinyl alcohol) to render it to be resistant to cell adhesion. As the cell culture medium could be replaced, spheroids of the human breast cancer (MCF-7) cells were cultured on the chip for 3 days, reaching the diameters of about 150 μm. Furthermore, the MCF-7 cells were successfully cultured on the chip in 2D and 3D culture modes. Results have shown that glass is well suitable for multicellular tumor spheroids culture. The established platform provides a convenient and rapid method for tumor spheroid culture, which is also adaptable for anticancer drug screening and fundamental biomedical research in cell biology.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant Nos. 21375152 and 21075139). The authors thank Dr. Karina Ziolkowska (Warsaw University of Technology, Department of Microbioanalytics, Warsaw, Poland), Dr. Dan Gao (The Key Laboratory of Chemical Biology, Tsinghua University, Shenzhen, China) for valuable discussion and Prof. Peiqing Liu (New Drug Screening Center, Sun Yat-sen University) for the help of cell culture.

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  1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China

    Duanping Sun, Jing Lu, Zuanguang Chen, Yanyan Yu & Yinbao Li

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  1. Duanping Sun
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Correspondence to Zuanguang Chen.

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Sun, D., Lu, J., Chen, Z. et al. A novel three-dimensional microfluidic platform for on chip multicellular tumor spheroid formation and culture. Microfluid Nanofluid 17, 831–842 (2014). https://doi.org/10.1007/s10404-014-1373-3

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  • DOI: https://doi.org/10.1007/s10404-014-1373-3

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