Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies
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s41598-018-22749-0.pdf
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Author(s)
Edington, Collin D
Chen, Wen Li
Geishecker, Emily R
Kassis, Timothy
Soenksen Martinez, Luis Ruben
Bhushan, Brij M
Maass, Christian Alexander
Tsamandouras, Nikolaos
Valdez Macias, Jorge Luis
Cook, Christi Dionne
Date Issued
March 2018
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Edington, Collin D. et al. “Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.” Scientific Reports 8, 1 (March 2018) © 2018 The Author(s)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Research Laboratory of Electronics
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Attribution 4.0 International (CC BY 4.0)
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DOI of Published Version
https://doi.org/10.1038/s41598-018-22749-0
