A closed-loop modular multiorgan-on-chips platform for self-sustaining and tightly controlled oxygenation.

Area of Science:

• Biotechnology
• Physiological Engineering
• Drug Discovery

Background:

• Physiological microenvironments are crucial for organ-on-a-chip (OOC) systems to accurately assess drug metabolism.
• Current OOC systems often use ambient incubator oxygen levels (21%), which are physiologically irrelevant compared to tissue-specific concentrations (0.5-13%).
• Oxygen levels significantly influence cellular and tissue functions and drug metabolism.

Purpose of the Study:

• To develop a closed-loop modular multiorgan-on-chips platform for real-time monitoring and precise control of oxygen levels.
• To enable independent adjustment of dissolved oxygen in the range of 4-20% across connected microtissues.
• To investigate the impact of controlled oxygen microenvironments on drug metabolism in OOC models.

Main Methods:

• Development of a modular multiorgan-on-chips platform integrating microfluidic oxygen scavengers, an oxygen generator, and a monitoring/controller system.
• Utilizing bioreactors for circulatory culture of connected microtissues.
• Performing drug studies on parallelly connected liver, kidney, and arterial vessel microtissues under controlled oxygen conditions.

Main Results:

• The platform successfully achieved real-time monitoring and tight control of oxygen levels (4-20%) in the culture medium.
• Demonstrated that oxygen levels significantly affect drug metabolism in liver, kidney, and arterial vessel microtissues.
• Showcased the platform's capability to provide physiologically relevant and independently adjustable oxygen microenvironments.

Conclusions:

• The developed platform enhances the physiological relevance of OOC systems by providing controlled oxygen microenvironments.
• This technology can improve the accuracy and performance of drug screening and metabolism studies.
• The platform supports both single- and multiorgan-on-a-chip configurations for diverse research needs.