Organ-on-Chip Vascular Network With Endothelial Barrier Perfusion

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Solution Overview

Problem

Current drug development processes are inefficient and lack predictive preclinical testing models, leading to high failure rates and safety issues due to the immaturity of human induced pluripotent stem cells and inadequate biological fidelity in existing screening models.

Innovation Solution

An integrated modular microphysiological system on a chip that includes multiple tissue types cultured in separate compartments with a vascular network, using endothelial barriers for communication and perfusion with a biocompatible material, allowing for customizable human physiological responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current preclinical testing models are used, then drug development can proceed through standard pipelines, but the models lack predictive accuracy and biological fidelity leading to high failure rates

Engineering Contradiction:

Improvepredictive accuracyVSAvoidmodel complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The system divides the human body into separate organ modules (heart, liver, kidney, etc.) that can be cultured independently in separate wells, then connected via a vascular network. This segmentation allows each organ to be optimized for its specific function while maintaining overall system complexity at a manageable level.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

An endothelial barrier layer is introduced as an intermediary between the tissue cultures and the vascular network channels. This barrier mimics the natural blood-tissue interface and enables physiologically relevant drug transport and interaction, significantly improving predictive accuracy without requiring complete system redesign.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If human induced pluripotent stem cells are used, then human-specific drug responses can be studied, but the cells are immature and lack biological fidelity

Engineering Contradiction:

Improvebiological fidelityVSAvoidcell maturity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

Tissues are cultured and matured in situ within the organ module wells before being integrated into the vascular network. This preliminary maturation phase allows cells to develop proper structure and function, achieving biological fidelity without sacrificing the versatility of using human iPSCs as the starting material.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If multiple tissue types are cultured together, then integrated physiological responses can be studied, but communication between tissues is inadequate

Engineering Contradiction:

Improvephysiological response accuracyVSAvoidtissue integration complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

A fluid-based vascular network is used to connect multiple tissue cultures, allowing nutrients, drugs, and signaling molecules to flow between organs in a manner that mimics the human circulatory system. This hydraulic approach enables realistic physiological responses without requiring direct physical contact between tissues.

Inventive Principle:

Principle #29Pneumatics and hydraulics

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Facilitates more accurate drug screening and safety testing by mimicking human circulatory systems, enabling efficient and cost-effective drug development with improved predictive capabilities.

Implementation Method 1

using an endothelial barrier the system enables the integration of multiple tissue types in a way that provides true separation to enable each tissue to be cultured in its specific culture media while still providing communication between tissues via a vascular network

Methodology Applied

Scientific EffectEndothelial barrier: Semipermeable Membrane

Implementation Method 2

Perfusion of a vascular medium, such as a blood substitute, through the entire system mimics the human circulatory system and allows for the introduction of drugs or circulating immune cells in a biomimetic manner

Methodology Applied

Scientific EffectPerfusion: Convection

Data Source

PatentUS12529022B2Human organ-on-chip models for predictive screening

Publication Date: 2026.01.20 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK

AI summary

An integrated modular microphysiological system is provided which includes a two or more chambers and a vascular network which includes at least one channel. The chamber can be configured for culturing a tissue and includes a layer of endothelial cells which forms an endothelial barrier within the well. The endothelial barrier can be in fluid contact with at least one of the at least one channels in the vascular network. The endothelial barrier can also be in fluid contact with a fluid in the chamber.