Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.

Area of Science:

• Biotechnology
• Pharmacology
• Bioengineering

Background:

• Microphysiological systems (MPSs) mimic in vivo organ function using advanced microenvironments.
• Current MPS models often lack the complexity to study multiple organs or drug interactions comprehensively.

Purpose of the Study:

• To develop and validate novel, re-usable microfluidic platforms for co-culturing multiple MPSs.
• To enable quantitative assessment of compounds, including lipophilic drugs, using interconnected MPSs.

Main Methods:

• Design and implementation of 4-way, 7-way, and 10-way microfluidic platforms with mixing chambers.
• Integration of on-board pneumatically-driven pumps for precise flow control and internal re-circulation.
• Co-culture of multiple MPSs for extended periods (up to 4 weeks) to assess stability and function.

Main Results:

• Demonstrated accurate prediction of secreted liver protein distribution in a 4-MPS system.
• Validated maintenance of MPS phenotypic markers for up to 4 weeks in 7-way and 10-way platforms.
• Successfully performed pharmacokinetic (PK) analysis of diclofenac metabolism in a multi-MPS configuration.

Conclusions:

• The developed microfluidic platforms support robust, long-term co-culture of multiple MPSs.
• This multi-MPS approach provides a generalizable "physiome-on-a-chip" strategy for drug discovery.
• The system facilitates quantitative compound studies and drug metabolism analysis, advancing in vitro modeling capabilities.