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  • Review Article
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Clamping strategies for organ-on-a-chip devices

Abstract

Organ-on-a-chip devices have enabled major breakthroughs in biomedical research, but they have yet to be successfully translated to the pharmaceutical industry. Traditional microfluidic devices rely on irreversible bonding techniques to seal fluidic channels, which limit their accessibility and automation and can be labour-intensive to operate. New and more versatile chip designs are urgently needed to enable industrial applications and to support complex, 3D cell cultures. Clamps allow microdevices to be opened and closed before, after and during operation, such that cells can be directly accessed whenever needed. This versatility facilitates the incorporation of more physiologically relevant 3D in vitro models, including organoids, and allows a wider range of on-chip and off-chip biochemical assays. This Review describes the current trend from irreversible chip bonding to innovative, reversible fastening techniques. We introduce the concept of Lock-and-Play devices as emerging tools that can provide a leak-tight seal in a single step for high-throughput applications. Finally, we analyse the applications in which Lock-and-Play devices are likely to have the biggest impact for the drug development industry.

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Fig. 1: Irreversible and reversible sealing strategies for organ-on-a-chip design.
Fig. 2: Clamping strategies to create reversibly sealed organ-on-a-chip devices.
Fig. 3: Examples of Lock-and-Play strategies.
Fig. 4: Culture of 3D biological models using clamping devices.
Fig. 5: Clamping strategies to decrease the use of elastomer-based gaskets.
Fig. 6: A roadmap towards the development of next-generation clamping devices.

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Acknowledgements

This study was financially supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement number 825745.

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D.J.T.C. wrote and edited the manuscript. L.M. supervised the manuscript and S.G. supervised and edited the manuscript.

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Correspondence to Stefan Giselbrecht.

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S.G. is founder and shareholder of 300MICRONS GmbH. D.J.T.C. and L.M. declare no competing interests.

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Teixeira Carvalho, D.J., Moroni, L. & Giselbrecht, S. Clamping strategies for organ-on-a-chip devices. Nat Rev Mater 8, 147–164 (2023). https://doi.org/10.1038/s41578-022-00523-z

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