PhysioMimix - Organ-on-a-chip Platform
Cell Culture
PhysioMimix™ for single-organ and multi-organ experiments with real-time control over cell culture condition to mimic in vivo physiology.
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Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.
Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs.
We describe three different platform designs – “4- way”, “7-way”, and “10-way” – each accommodating a mixing chamber and up to 4, 7, or 10 MPSs.Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution.
We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS “physiome-on-a-chip” approaches in drug discovery…
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Microphysiological systems for studying interactions between the liver, gut and immune system.
Microphysiological systems (MPS), also known as organ-on -chips, are small scale in vitro cell cultures which mimic facets of tissue or organ function. MPS frequently utilise primary human cells, cultured in scaffolds, to obtain highly functional, physiologically relevant models…
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Peer-reviewed Scientific Articles
- Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies AAPS J, 2017; 19: 1499. doi: 10.1208/s12248-017-0122-4
- Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies Scientific Reports, 2018; 8(1):8015. doi: 10.1038/s41598-018-25971-y.
- Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies Nature Scientific Reports, 2018; 4;8(1):4530. doi: 10.1038/s41598-018-22749-0.
- Integrated Gut/Liver Microphysiological Systems Elucidates Inflammatory Inter-Tissue Crosstalk Biotechnology and Bioengineering, 2017; 114(11):2648-2659. doi: 10.1002/bit.26370.
- Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS) Integr. Biol., 2017; 9(4):290-302. doi: 10.1039/c6ib00243a.
- Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration CPT: pharmacometrics & systems pharmacology, 2015; 4, 585-594. doi: 10.1002/psp4.12010.
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- Cell Culture