Plastic Fluid Culture Medium for Low-Stress Cell Oxygenation

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Solution Overview

Problem

Aeration by bubbling in animal cell culture is challenging due to shear stress and foaming issues, particularly in large volumes, which limits oxygen supply and is impractical for regenerative medicine applications where low physical stress is required.

Innovation Solution

A cell culturing method using a plastic fluid culture medium with air bubbles introduced to reduce physical stress and enhance oxygen supply, allowing for suspended cell culture even in large volumes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If bubbling is applied to increase oxygen supply, then oxygen mass transfer is improved, but shear stress damages the cells

Engineering Contradiction:
Improveoxygen concentrationVSAvoidshear stress
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

A perfluorocarbon compound is introduced as an intermediary substance that acts as an oxygen carrier in the culture medium. This mediator enables oxygen transport without requiring direct gas-liquid contact through bubbling, thereby avoiding shear stress on cells while still achieving sufficient oxygen supply

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical composition parameter of the culture medium by adding a perfluorocarbon compound with high oxygen solubility. This parameter change allows the medium to carry dissolved oxygen at higher concentrations without needing mechanical aeration, thus preventing shear stress damage to sensitive animal cells

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If surface aeration method is used, then oxygen transfer occurs at gas-liquid interface, but gas-liquid interfacial area per unit volume decreases as culture solution volume increases

Engineering Contradiction:
Improveoxygen supplyVSAvoidgas-liquid interfacial area per unit volume
Core Design Contradiction:
Quantity of substanceVSArea of stationary object

Solution Approach 1:

The patent changes the physical-chemical parameter of the culture medium by incorporating a perfluorocarbon compound that dramatically increases oxygen solubility. This allows sufficient oxygen supply even with limited gas-liquid interfacial area, making the system scalable to large culture volumes without relying on extensive surface aeration

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If hydrophobic membrane tubes are arranged in culture medium, then gas-liquid interfacial area per unit volume increases, but culture tank inner structure becomes complicated and contamination risk increases

Engineering Contradiction:
Improvegas-liquid interfacial areaVSAvoidculture tank inner structure
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent extracts the function of oxygen transfer from the mechanical structure (membrane tubes, spargers) and transfers it to the chemical composition of the culture medium itself. By using a perfluorocarbon-based medium that inherently carries dissolved oxygen, the complex aeration structures are eliminated, simplifying the culture system and reducing contamination risks

Inventive Principle:
Principle #2Taking out (Extraction)

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

This method effectively suppresses physical stress and improves oxygen supply, enabling mass culture of sensitive cells like those used in regenerative medicine and plant cells by extending air bubble residence time and increasing gas holdup without convective stress.

Implementation Method 1

enabling mass culture of cells that are sensitive to physical stress, such as cells that are used for regenerative medicine and plant cells

Methodology Applied
Scientific EffectGas holdup:

Implementation Method 2

Oxygen can be said to be a nutritional component that cannot be maintained at a sufficiently high concentration in the solution

Methodology Applied
Scientific EffectOxygen mass transfer:

Data Source

PatentUS10954487B2Cell culturing method
Publication Date: 2021.03.23 OSAKA UNIVERSITY
  • US10954487B2 patent drawing
  • US10954487B2 patent drawing
  • US10954487B2 patent drawing

AI summary

Provided is a cell culturing method in which physical stress is reduced and oxygen can be supplied. The invention relates to a cell culturing method including; arranging cells in a dispersed state in a culture medium which is a plastic fluid; and introducing air bubbles into said culture medium.