Hollow Fiber Bioreactor Membrane Assembly

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Solution Overview

Problem

Current methods for treating synthetic membrane surfaces in bioreactors using gamma irradiation to enhance cell adherence often result in the formation of cytotoxic products that damage the bioreactor housing, requiring extensive rinsing to remove, which is time-consuming and increases the risk of contamination.

Innovation Solution

Treating the membrane with a combination of gamma radiation and gas plasma before assembling it into the polymeric casing avoids exposing the housing to electromagnetic radiation, thereby preventing the formation of cytotoxic products and allowing direct cell attachment without further surface modification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gamma irradiation is used to treat synthetic membrane surfaces to enhance cell adherence, then cell adherence is improved, but cytotoxic products are formed that damage the bioreactor housing

Engineering Contradiction:
Improvecell adherenceVSAvoidcytotoxic products
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent divides the bioreactor into two separate treatment stages: first treating the membrane fibers with gamma irradiation to enhance cell adherence, then assembling them into the housing. This segmentation prevents the housing from being exposed to radiation, thereby avoiding cytotoxic product formation while maintaining membrane surface treatment effectiveness.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The membrane fibers are pre-treated with gamma irradiation and plasma treatment before assembly into the housing. This preliminary action ensures the membrane surface is optimized for cell adherence without subjecting the housing to radiation, thus preventing cytotoxic effects on the housing material.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If high doses of radiation are used to modify membrane surfaces, then cell adherence is enhanced, but the bioreactor housing may be damaged

Engineering Contradiction:
Improvecell adherenceVSAvoidhousing integrity
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The patent separates the radiation treatment step from the housing assembly step. The membrane fibers receive high-dose gamma irradiation before assembly, while the housing is assembled first and then the bundle is irradiated as a complete unit. This segmentation ensures the housing is not exposed to radiation, preserving its structural integrity while maintaining membrane treatment effectiveness.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses plasma treatment as an intermediary step between membrane production and final assembly. The membranes are treated with plasma to enhance cell adherence, then assembled into the housing. This intermediary approach allows surface modification without requiring the housing to be exposed to radiation, thus protecting housing integrity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If extensive rinsing is performed to remove cytotoxic products, then cell safety is improved, but time and material usage increase

Engineering Contradiction:
Improvecell safetyVSAvoiddecontamination time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent performs plasma treatment on the membrane fibers immediately after gamma irradiation and before assembly into the housing. This preliminary action modifies the membrane surface to enhance cell adherence while preventing cytotoxic product formation in the first place, thereby eliminating the need for extensive post-assembly rinsing procedures.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent converts the potentially harmful effect of gamma irradiation on the housing into a beneficial process by using it to treat the membrane fibers before assembly. The radiation that would otherwise damage the housing is instead used to modify the membrane surface, and plasma treatment is applied subsequently to enhance cell adherence without requiring extensive decontamination.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

4Object-generated harmful factors

If multiple rinsing steps are used to remove toxic products, then cytotoxicity is reduced, but contamination risk increases

Engineering Contradiction:
ImprovecytotoxicityVSAvoidcontamination risk
Core Design Contradiction:
Object-generated harmful factorsVSObject-affected harmful factors

Solution Approach 1:

The patent applies plasma treatment to the membrane fibers immediately after gamma irradiation and before assembly. This preliminary action modifies the membrane surface to enhance cell adherence and prevents cytotoxic product formation, thereby eliminating the need for multiple rinsing steps that would otherwise be required to remove toxic products.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent converts the potential harm of radiation-induced cytotoxic products into a benefit by using gamma irradiation to treat the membrane fibers before assembly, followed by plasma treatment to enhance cell adherence. This approach prevents cytotoxicity without requiring extensive rinsing, thereby reducing contamination risk associated with multiple rinsing steps.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 minimizes the need for extensive decontamination procedures, reduces material usage, and lowers the risk of contamination, while enabling efficient cell growth by ensuring a safe and optimized environment for adherent cells.

Implementation Method 1

Gamma irradiation, electron beam graft polymerization and plasma treatment are examples of procedures used to chemically modify the membrane surface using radiation for cell adherance

Methodology Applied
Scientific EffectGamma radiation: Radiation

Implementation Method 2

Gamma irradiation, electron beam graft polymerization and plasma treatment are examples of procedures used to chemically modify the membrane surface using radiation for cell adherance

Methodology Applied
Scientific EffectGas plasma: Plasma

Data Source

PatentEP2488629B1Method of assembling a hollow fiber bioreactor
Publication Date: 2020.03.11 TERUMO BCT INC
  • EP2488629B1 patent drawingFigure 1~3
  • EP2488629B1 patent drawingFigure 4

AI summary

The present invention relates to a method of assembling a cell growth module, and preventing the formation of cytotoxic chemicals in the cell growth module which may interfere with the growth of the cells in the cell growth module. Electromagnetic radiation such as gamma irradiation may be used to treat the membrane surface prior to the membrane being inserted into the housing. The cell growth module includes at least a membrane and a housing.