Fluidic Programmable Gravi-maze Array for High Throughput Multiorgan Drug Testing.

Area of Science:

• Biomedical Engineering
• Translational Medicine
• Preclinical Research

Background:

• High attrition rates in clinical trials necessitate more predictive preclinical models.
• 2D cell cultures and animal models lack physiological relevance for human responses.
• Need for high-throughput multiorgan interaction modeling drives MOAP platform development.

Purpose of the Study:

• Introduce OrganRX™, a modular, gravity-driven multiorgan-on-a-plate (MOAP) system.
• Replicate human organ function, fluid dynamics, and inter-organ communication in vitro.
• Provide a scalable platform for preclinical drug evaluation and disease modeling.

Main Methods:

• Developed a microfluidic architecture using Fluidic Programmable Gravi-maze Array (FPGA) integrating gut, liver, kidney, brain, and endothelium.
• Utilized computational fluid dynamics (CFD) and impedance-based flow validation for shear control.
• Constructed organ-specific and multiorgan models with 3D extracellular matrix hydrogels for metabolism and senescence assessment.

Main Results:

• Confirmed accurate shear stress control across organ compartments.
• Demonstrated metabolic interplay between liver-kidney co-cultures via albumin and urea production.
• Revealed context-specific drug interactions in a gut-brain model, with curcumin reversing phenylbutyrate's effect on brain ROS.

Conclusions:

• OrganRX™ offers a physiologically relevant, scalable, and automation-compatible MOAP platform.
• The system captures complex, dynamic inter-organ effects crucial for drug evaluation.
• OrganRX™ advances translational research and precision medicine by improving preclinical model accuracy.