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  • Review Article
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Microfluidic high-throughput 3D cell culture

Abstract

High-throughput 3D microfluidic cell culture systems can be designed to model aspects of human tissues and organs and may thus serve as non-clinical evaluation tools. They benefit from large-scale production, high throughput, compatibility with automated equipment, standardized analysis and the generation of physiologically relevant results. In this Review, we discuss how microfluidic devices can be designed with different biological complexity, cell sources and cell configurations, as well as physiological parameters to mimic human tissues. We examine standardization, scalability and automation strategies, and outline high-throughput data generation and analysis approaches to interpret readouts of microfluidic 3D cell culture models. Finally, we explore the potential of these tools as non-clinical testing systems for drug development and outline key future challenges in device design and application.

Key points

  • High-throughput microfluidic 3D cell culture systems may provide valuable non-clinical testing tools.

  • To apply microfluidic technology in cell culture, physiological relevance and high throughput need to be balanced.

  • Microfluidics-based 3D cell culture models can be designed and optimized for specific applications, depending on the required level of biological complexity and readout.

  • Automation and artificial intelligence may aid in the standardized analysis of 3D microfluidic cell culture devices.

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Fig. 1: Microfluidic high-throughput 3D cell culture.
Fig. 2: Design considerations for microfluidic 3D cell culture platforms.

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Acknowledgements

This work was supported by National Research Foundation of Korea grants funded by the Korean government (MSIT) (no. 2021R1A3B1077481 to N.L.J.; RS-2023-00253722 to J.K.; RS-202300222838 to J.L.).

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N.L.J. conceived, wrote and edited the manuscript. All authors contributed to the writing of the manuscript. K.S. provided insights from a regulatory perspective. K.B. offered an industry viewpoint. J.L. shared clinical insights.

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K.B. discloses a relationship with Qureator, Inc., which encompasses participation on the board, employment, and ownership of equity or stocks. N.L.J. discloses an affiliation with Qureator, Inc., involving board membership and ownership of equity or stocks. The other authors declare no competing interests. The opinions expressed in this article are those of the authors and may not necessarily reflect those of the FDA.

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Ko, J., Park, D., Lee, J. et al. Microfluidic high-throughput 3D cell culture. Nat Rev Bioeng 2, 453–469 (2024). https://doi.org/10.1038/s44222-024-00163-8

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