Bioreactor Oxygen Delivery via Permeable Membrane

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Solution Overview

Problem

Current bioreactor technologies face challenges in efficiently delivering oxygen to high-cell-density animal cell cultures without causing oxidative stress, as traditional methods like agitation and bubbling can lead to shear forces and oxygen excess, which damages cells and reduces viability.

Innovation Solution

A bioreactor design incorporating an oxygen-carrying molecule receptacle with an oxygen-permeable membrane allows for controlled oxygen delivery using hemoglobin-based oxygen carriers or extracellular hemoglobins, which release oxygen based on a partial pressure gradient, avoiding direct contact and shear forces.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If agitation or bubbling is used to supply oxygen, then oxygen delivery is improved, but shear forces damage cell membranes and reduce cell viability

Engineering Contradiction:

Improveoxygen deliveryVSAvoidshear forces on cell membranes

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent uses an oxygen-permeable membrane as an intermediary to transfer oxygen from the gas phase to the liquid culture medium without direct contact between bubbles/agitation and cells. The membrane acts as a mediator that enables oxygen delivery while eliminating shear forces that would otherwise damage cell membranes.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces mechanical oxygen delivery methods (agitation and bubbling) with a diffusion-based system through an oxygen-permeable membrane. This substitution eliminates the mechanical shear forces associated with traditional methods while maintaining effective oxygen supply to the cell culture.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If high levels of dissolved oxygen are provided, then oxygen supply is improved, but oxidative stress damages cellular materials and reduces cell viability

Engineering Contradiction:

Improvedissolved oxygen levelVSAvoidoxidative stress and free radicals

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The system provides continuous oxygen supply through the membrane, allowing dissolved oxygen levels to self-regulate based on cell consumption rates. This feedback mechanism prevents oxygen accumulation to harmful levels while ensuring adequate supply, as the membrane permits oxygen to diffuse through in response to the partial pressure gradient created by cellular respiration.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The oxygen-permeable membrane enables the culture system to self-regulate oxygen levels through passive diffusion driven by the partial pressure gradient between the gas phase and liquid phase. The system automatically adjusts oxygen delivery to match cellular demand without external control, preventing both oxygen deficiency and oxidative stress.

Inventive Principle:

Principle #25Self-service

3Productivity

If high cell density is maintained for increased productivity, then output is improved, but oxygen demand increases and becomes difficult to meet without causing harm

Engineering Contradiction:

Improvecell density and product outputVSAvoidoxygen demand

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The oxygen-permeable membrane is pre-installed in the bioreactor system, establishing a continuous oxygen supply pathway before high cell density is achieved. This preliminary preparation ensures that as cell density increases and oxygen demand rises, the membrane is already in place to meet the increased demand through enhanced diffusion, preventing oxygen limitation and associated cellular stress.

Inventive Principle:

Principle #10Preliminary action

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 approach enhances oxygen diffusion efficiency, reduces oxidative stress, and maintains cell viability by matching oxygen supply with cellular demand, improving cell growth and productivity in high-density cultures.

Implementation Method 1

oxygen can be delivered to the cells progressively according to the biomass growth avoiding stress and cell damages linked to oxygen excess

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 2

oxygen-carrying molecules, which release oxygen based on a partial pressure gradient

Methodology Applied

Scientific EffectPartial pressure gradient: Pressure Gradient

Implementation Method 3

using hemoglobin-based oxygen carriers or extracellular hemoglobins, which release oxygen based on a partial pressure gradient

Methodology Applied

Scientific EffectOxygen binding and release: Absorption (physical)

Data Source

PatentUS10119110B2Bioreactor using oxygen-carrying molecules

Publication Date: 2018.11.06 HEMARINA

AI summary

The present invention relates to devices and bioreactors capable of delivering oxygen to a cell culture using oxygen-carrying molecules. The bioreactor comprises at least two chambers separated by an oxygen-permeable membrane. The oxygen-carrying molecules are chosen from extracellular hemoglobin isolated from worm belonging to Arenicoliolae family or Nereidiolae family.