Design and demonstration of a pumpless 14 compartment microphysiological system

Area of Science:

• Biotechnology
• Bioengineering
• Physiological Modeling

Background:

• Current drug development faces challenges in predicting in vivo pharmacokinetics and pharmacodynamics.
• Microphysiological systems offer a promising alternative to traditional animal models for studying human physiology and drug responses.
• Existing models often lack the complexity to fully replicate multi-organ interactions and barrier functions.

Purpose of the Study:

• To describe the design and operation of a 14-chamber microfluidic "Body-on-a-chip" device.
• To emulate drug distribution, metabolism, and action by mimicking multi-organ interactions.
• To assess the viability and functionality of diverse cell lines within the system over time.

Main Methods:

• Development of a pumpless, gravity-driven microfluidic device with 14 chambers representing 13 human organs.
• Incorporation of barrier (skin, GI, lung) and non-barrier (fat, kidney, liver, etc.) tissue chambers.
• Utilized specific cell lines (A549, Caco2, HepG2 C3A, Meg01, HK2) and hydrogels (PGMatrix) for organ representation.
• Designed channel dimensions and flow rates based on human physiological data for accurate fluid retention times.
• Operated the system on a custom rocker platform to induce flow and minimize bubble formation.

Main Results:

• Demonstrated high viability (>85%) for five different cell lines over a 7-day culture period.
• Successfully mimicked barrier functions, allowing controlled passage of reagents to non-barrier tissues.
• Validated the system's ability to measure key cellular functions, including CYP450 enzyme activity, albumin and urea production, tight junction maintenance, and surfactant presence.
• Observed flow rates within compartments closely matched estimated physiological flow rates.

Conclusions:

• The developed "Body-on-a-chip" system is a feasible and effective platform for studying multi-organ interactions and drug responses.
• The gravity-driven, pumpless design simplifies operation and maintenance while ensuring sustained cellular function.
• This microphysiological system holds significant potential for advancing drug discovery and personalized medicine by providing a more accurate human-relevant model.