Engineering challenges for instrumenting and controlling integrated organ-on-chip systems

Area of Science:

• Biotechnology
• Systems Biology
• Microfluidics

Background:

• Recent advances in microfabrication enable sophisticated organs-on-chips and human organ constructs.
• These technologies facilitate the design of scaled, interconnected organ systems for enhanced drug development and systems biology.

Purpose of the Study:

• To engineer physiologically realistic live microHuman (μHu) and milliHuman (mHu) systems for extended operation (weeks to months).
• To address key engineering challenges in creating functional, scaled organ systems for research and development.

Main Methods:

• Developing low-volume microdevices with capabilities for chemical signaling, microfluidic pumps, and valves.
• Integrating automated optical microscopy, electrochemical sensors, and ion mobility-mass spectrometry for real-time analysis.
• Utilizing advanced bioinformatics and machine learning for automated model inference and system control.

Main Results:

• Engineering challenges include determining organ size, cell density, perfusion media, physiological sensing, and system control.
• Maintaining precise fluid scaling for both μHu (~5 μL) and mHu (~5 mL) systems.
• Building functional prototype components for eventual top-down system integration.

Conclusions:

• Successful μHu and mHu systems require a multidisciplinary approach integrating microfluidics, advanced sensing, and AI.
• These systems hold significant potential to augment the drug development pipeline and advance systems biology research.
• Ongoing work focuses on component prototyping and system integration to achieve functional organ systems.