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Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.


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.

SUBMITTER: Edington CD 

PROVIDER: S-EPMC5852083 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.

Edington Collin D CD   Chen Wen Li Kelly WLK   Geishecker Emily E   Kassis Timothy T   Soenksen Luis R LR   Bhushan Brij M BM   Freake Duncan D   Kirschner Jared J   Maass Christian C   Tsamandouras Nikolaos N   Valdez Jorge J   Cook Christi D CD   Parent Tom T   Snyder Stephen S   Yu Jiajie J   Suter Emily E   Shockley Michael M   Velazquez Jason J   Velazquez Jeremy J JJ   Stockdale Linda L   Papps Julia P JP   Lee Iris I   Vann Nicholas N   Gamboa Mario M   LaBarge Matthew E ME   Zhong Zhe Z   Wang Xin X   Boyer Laurie A LA   Lauffenburger Douglas A DA   Carrier Rebecca L RL   Communal Catherine C   Tannenbaum Steven R SR   Stokes Cynthia L CL   Hughes David J DJ   Rohatgi Gaurav G   Trumper David L DL   Cirit Murat M   Griffith Linda G LG  

Scientific reports 20180314 1


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",  ...[more]

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