Multi-Chamber Bioreactor with Semi-Permeable Membrane

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Solution Overview

Problem

Current co-culture systems fail to effectively model the dynamic biochemical interactions and mechanical environments of in vivo tissues, limiting the development of viable three-dimensional cellular constructs for medical applications, as they often lack physical separation of cell types and uniform biochemical communication.

Innovation Solution

A multi-chambered bioreactor system with semi-permeable membranes and independent control of environmental factors, allowing biochemical communication while maintaining physical separation of cell types, and capable of subjecting cells to mechanical stimuli like shear stress and hydrostatic loading.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If cells are physically separated using a porous substrate, then cell type isolation is improved, but flow characteristics and biochemical communication are altered

Engineering Contradiction:
Improvecell type isolationVSAvoidbiochemical communication
Core Design Contradiction:
Manufacturing precisionVSEase of operation

Solution Approach 1:

A non-porous separation membrane is introduced as an intermediary between cell cultures. This membrane allows biochemical substances to pass through while preventing cell migration, thus maintaining both cell isolation and natural biochemical communication without the flow-altering effects of porous substrates.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent specifically avoids using porous substrates for cell support, instead employing non-porous separation membranes. This design choice prevents the substrate from absorbing or altering biochemical flows, maintaining natural diffusion and convection patterns for cell communication.

Inventive Principle:
Principle #31Porous materials

2Device complexity

If a single culture medium is used for all cell types, then system simplicity is improved, but specific biochemical needs of different cell types cannot be met

Engineering Contradiction:
Improvesystem simplicityVSAvoidcell type specific culture conditions
Core Design Contradiction:
Device complexityVSAdaptability or versatility

Solution Approach 1:

The culture system is segmented into multiple independent chambers, each capable of receiving its own specialized culture medium. This segmentation allows different cell types to be cultured under their specific biochemical conditions while maintaining a relatively simple overall system architecture.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Each culture chamber is designed to have its own local culture environment with tailored medium composition, pH, and other parameters optimized for specific cell types. This local quality approach enables customized culture conditions without requiring complex system-wide modifications.

Inventive Principle:
Principle #3Local quality

3Productivity

If cells are in physical contact with a support scaffold, then cell attachment and growth are improved, but flow characteristics of biochemicals are altered

Engineering Contradiction:
Improvecell growthVSAvoidbiochemical flow characteristics
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

A non-porous separation membrane serves as an intermediary that supports cell attachment and growth while maintaining natural biochemical flow characteristics. The membrane provides structural support for cells without the flow-altering properties of porous materials.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 growth and development of isolated, three-dimensional cellular constructs with improved purity and biochemical communication, facilitating the study of cell interactions and potential medical applications such as tissue engineering and stem cell differentiation.

Implementation Method 1

The systems can include a first culture chamber in biochemical communication with a second culture chamber, with a semi-permeable membrane separating the first and second chambers

Methodology Applied
Scientific EffectSemi-permeable membrane separation: Semipermeable Membrane

Implementation Method 2

fluid perfusion through a culture chamber can subject developing cells to shear stress

Methodology Applied
Scientific EffectShear stress: Shear Stress

Implementation Method 3

an adjacent pressure module can be utilized to subject the interior of a culture chamber to hydrostatic loading

Methodology Applied
Scientific EffectHydrostatic loading: Pressure Increase

Data Source

PatentEP1913126B1Co-culture bioreactor system
Publication Date: 2019.09.25 CLEMSON UNIV RES FOUND
  • EP1913126B1 patent drawingFigure 1
  • EP1913126B1 patent drawingFigure 2
  • EP1913126B1 patent drawingFigure 3

AI summary

Disclosed are multi-chambered cell co-culture systems. The systems can be utilized to encourage the growth and development of isolated cells in a dynamic three-dimensional in vitro environment. The cell chambers (10) of the system can be in biochemical communication with adjacent chambers containing cells of different types, but the different cell types are maintained physically separated from one another. In addition, the local environment of each cell chamber can be independently controlled. For example, fluid flow characteristics through a single cell chamber can be independently controlled and maintained for each separate chamber of the system.