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Microfluidic organs-on-chips

Abstract

An organ-on-a-chip is a microfluidic cell culture device created with microchip manufacturing methods that contains continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology. By recapitulating the multicellular architectures, tissue-tissue interfaces, physicochemical microenvironments and vascular perfusion of the body, these devices produce levels of tissue and organ functionality not possible with conventional 2D or 3D culture systems. They also enable high-resolution, real-time imaging and in vitro analysis of biochemical, genetic and metabolic activities of living cells in a functional tissue and organ context. This technology has great potential to advance the study of tissue development, organ physiology and disease etiology. In the context of drug discovery and development, it should be especially valuable for the study of molecular mechanisms of action, prioritization of lead candidates, toxicity testing and biomarker identification.

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Figure 1: Fabrication methods for microfluidic chips.

Kim Caesar/Nature Publishing Group

Figure 2: Examples of increasingly complex single-channel, organ-on-chip designs.

Katie Vicari/Nature Publishing Group

Figure 3: Microfluidic chip models of angiogenesis and immune cell invasion that incorporate ECM gels.
Figure 4: Examples of increasingly complex organ-on-chip designs.
Figure 5: A multi-organ microfluidic framework used for PK/PD modeling.

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Acknowledgements

We thank H. Fleming, S. Khetani, D. Levner, G. Hamilton and T. Bahinski for their helpful input. This work was supported by grants from the Defense Advanced Research Projects Agency (DARPA) (W911NF-12-2-0036), the FDA (HHSF223201310079C), the US National Institutes of Health (UH3 EB017103, R01 DK85713, R01 EB008396), Bill and Melinda Gates Foundation (OPP1023607, OPP1086223) and the Wyss Institute for Biologically Inspired Engineering at Harvard University. S.N.B. is an investigator of the Howard Hughes Medical Institute; D.E.I. is a recipient of a US Department of Defense (DoD) Breast Cancer Innovator Award (BC074986).

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Correspondence to Donald E Ingber.

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S.N.B. is a co-founder of Hepregen Corporation, and D.E.I. is a founder of Emulate Inc.

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Bhatia, S., Ingber, D. Microfluidic organs-on-chips. Nat Biotechnol 32, 760–772 (2014). https://doi.org/10.1038/nbt.2989

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