Modular Bioreactor With Permeable Membranes For Multi-Tissue Media Isolation

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Solution Overview

Problem

Current bioreactors for multi-tissue in vitro culture primarily use a two-dimensional approach, which is not physiologically relevant, and lack the ability to efficiently exchange tissue-specific media without mixing, limiting their effectiveness in drug testing and disease modeling.

Innovation Solution

A modular bioreactor system that allows for the configuration of multiple tissue types connected by perfused microfluidic conduits, enabling the simultaneous delivery of specific media to each tissue type while maintaining separation through permeable membranes and pillars, mimicking in vivo physiology and vascular interactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a two-dimensional approach is used for multi-tissue in vitro culture, then the bioreactor structure is simple and easy to manufacture, but the physiological relevance is poor and tissue maturity is limited

Engineering Contradiction:
Improvephysiological relevanceVSAvoidbioreactor structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent transitions from two-dimensional tissue culture to three-dimensional microtissue engineering by incorporating vertical pillars with central channels that extend through the tissue construct. This 3D architecture enables physiological relevance by mimicking in vivo tissue organization and vascularization, while the modular pillar design maintains manufacturing feasibility through standardized components.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Reliability

If tissue-specific media is delivered to multiple tissue types simultaneously, then each tissue receives optimal nutrients, but the media sources may mix and compromise tissue specificity

Engineering Contradiction:
Improvetissue-specific media deliveryVSAvoidmedia flow path
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The bioreactor divides the media delivery system into separate, dedicated flow paths for each tissue type. Each tissue well has its own media inlet and outlet ports, preventing cross-contamination between different tissue cultures. This segmentation enables simultaneous delivery of multiple tissue-specific media while maintaining complete isolation between media sources.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces permeable membranes as intermediaries between the media reservoirs and tissue cultures. These membranes selectively allow nutrient and gas exchange while preventing direct mixing of media from different tissue sources, thus maintaining media specificity through a physical barrier that enables controlled interaction.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If three-dimensional microtissues with internal cavities are engineered, then physiological relevance and vascular network integration are improved, but media access to internal regions becomes more difficult

Engineering Contradiction:
Improvevascular network integrationVSAvoidmedia access
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent extracts the media delivery function from the surrounding environment and places it directly into the center of the 3D microtissue by incorporating central channels within supporting pillars. These internal channels act as artificial vasculature, directly delivering media to the core of the tissue construct and eliminating the diffusion limitations inherent in solid 3D structures.

Inventive Principle:
Principle #2Taking out (Extraction)

4Productivity

If multiple tissue types are cultured in the same reactor, then resource utilization is efficient, but cross-contamination between tissues may occur

Engineering Contradiction:
Improveresource utilizationVSAvoidtissue isolation
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The bioreactor is divided into multiple independent wells, each capable of housing a different tissue type. Each well functions as an isolated culture chamber with dedicated media flow paths, allowing simultaneous cultivation of multiple tissue types in a single reactor while preventing cross-contamination through physical separation barriers.

Inventive Principle:
Principle #1Segmentation

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

Enables the creation of functional, three-dimensional adult-phenotype microtissues with integrated vascular networks, facilitating more accurate drug testing and disease modeling by providing a physiologically relevant environment for tissue growth and interaction.

Implementation Method 1

at least a portion of each second pillar or the horizontal segment is formed of a permeable membrane. The permeable membrane, for example, can have a permeability of three microns or less.

Methodology Applied
Scientific EffectPermeation: Permeation

Data Source

PatentUS11261413B2Bioreactor system for engineering tissues
Publication Date: 2022.03.01 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
  • US11261413B2 patent drawing
  • US11261413B2 patent drawing
  • US11261413B2 patent drawing

AI summary

A bioreactor is provided that permits engineering of multiple different tissues. The bioreactor has a series of flow paths that permit application of tissue-specific media while simultaneously innervating the various different tissues with a common media. The flow paths for the various medias are designed to prevent mixing of the various media as they simultaneously innervate the tissue.