Robotic fluidic coupling and interrogation of multiple vascularized organ chips

Area of Science:

• Biotechnology
• Physiology
• Pharmacology

Background:

• Organ chips offer in vitro recapitulation of organ physiology but lack integrated vascular perfusion for multi-organ studies.
• Pharmacokinetic (PK) and pharmacodynamic (PD) analyses necessitate interconnected organ systems to mimic systemic circulation.

Purpose of the Study:

• To develop an automated platform for culturing, perfusing, and fluidically linking multiple organ chips.
• To enable advanced PK/PD studies and in situ imaging within a multi-organ system.

Main Methods:

• A robotic 'interrogator' system was designed using liquid-handling robotics, custom software, and a mobile microscope.
• The system automated culture, perfusion, medium addition, fluidic linking, and sample collection for up to ten organ chips.
• Eight vascularized organ chips (intestine, liver, kidney, heart, lung, skin, blood-brain barrier, brain) were maintained for 3 weeks in fluidic connection.

Main Results:

• The robotic interrogator successfully maintained the viability and organ-specific functions of interconnected organ chips for 3 weeks.
• Quantitative prediction of tracer distribution (inulin) was achieved using the system and a reduced-order model.
• Automated in situ imaging and compartment sampling were performed without compromising fluidic coupling.

Conclusions:

• The automated platform facilitates the creation and study of complex multi-organ-on-chips systems.
• This technology advances in vitro modeling for PK/PD studies, drug development, and disease research.
• The system supports long-term culture and analysis of interconnected organoids, enhancing physiological relevance.