Fluorine-Containing Cyclic Olefin Polymer Substrate for Cell Culture

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Solution Overview

Problem

Current cell culture methods face challenges in efficiently culturing adherent cells without damaging them, particularly due to the complexity of subculture operations and the use of substrates that can lead to cell damage during separation, and there is a need for substrates that maintain drug metabolizing enzyme activity over a long period.

Innovation Solution

A medical instrument with a substrate surface formed from a fluorine-containing cyclic olefin polymer, which allows cells to be easily floated and separated without damage, maintaining drug metabolizing enzyme activity for extended periods, and features a water contact angle between 70° and 160° to reduce cell adhesion and facilitate colony formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional substrates (polystyrene, collagen) are used for cell culture, then cell adhesion and proliferation are supported, but cell damage occurs during separation and subculture operations

Engineering Contradiction:
Improvecell integrityVSAvoidsubculture operation complexity
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The invention changes the surface energy parameters of the substrate by using fluorine-containing cyclic olefin polymer, which has inherently low surface energy and hydrophobic properties. This parameter change allows cells to be cultured without strong adhesion, enabling easy separation without cell damage while maintaining culturing functionality

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses a composite approach by combining fluorine-containing cyclic olefin polymer with specific surface treatments (plasma treatment, corona treatment, or UV irradiation) to create a substrate that balances cell adhesion during culturing with easy separation during subculture operations

Inventive Principle:
Principle #40Composite materials

2Productivity

If strong adhesion substrates are used to support cell proliferation, then cell growth is enhanced, but cell separation becomes difficult and damaging

Engineering Contradiction:
Improvecell proliferation efficiencyVSAvoidcell damage during separation
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The fluorine-containing cyclic olefin polymer substrate has controlled surface energy parameters that provide sufficient adhesion for cell proliferation while preventing excessive adhesion that would cause damage during separation. The water contact angle is controlled within 70-160° to achieve this balance

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The substrate is designed to be used for a specific purpose (cell culturing) and then easily discarded or regenerated after cells are harvested, eliminating the need for complex regeneration of adhesion properties and reducing cell damage from repeated use

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Productivity

If frequent subculture operations are performed to maintain cell concentration, then cell culture productivity is maintained, but cell damage and operation complexity increase

Engineering Contradiction:
Improvecell culture efficiencyVSAvoidsubculture operation time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The substrate enables a self-service approach where cells can be easily harvested by simple rinsing with buffer solution without requiring complex manual operations like scraping or trypsin treatment, significantly reducing operation time and labor

Inventive Principle:
Principle #25Self-service

4Reliability

If hydrophilic substrates are used to enhance cell adhesion, then cell attachment is improved, but cell separation becomes more difficult

Engineering Contradiction:
Improvecell attachment stabilityVSAvoidcell separation ease
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The invention inverts the conventional approach by using a hydrophobic substrate (water contact angle 70-160°) instead of hydrophilic. The fluorine-containing cyclic olefin polymer provides controlled hydrophobicity that allows cell attachment through culture medium components while enabling easy separation due to reduced direct cell-substrate adhesion

Inventive Principle:
Principle #35Parameter changes

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

The fluorine-containing cyclic olefin polymer substrate enables effective cell culture by preventing cell damage during separation and maintaining enzyme activity for at least 7 days, allowing for efficient cell proliferation and colony formation while reducing adhesion to the substrate.

Implementation Method 1

a fluorine-containing cyclic olefin polymer which has a water contact angle of 70° to 160°

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 2

cells are in contact with or held on a surface of the substrate

Methodology Applied
Scientific Effectvan der Waals force: Van der Waals Force

Data Source

PatentUS11597910B2Medical instrument, cell culture method, fluorine-containing cyclic olefin polymer and fluorine-containing cyclic olefin polymer composition for it, and cultured cells
Publication Date: 2023.03.07 MITSUI CHEMICALS INC
  • US11597910B2 patent drawing
  • US11597910B2 patent drawing
  • US11597910B2 patent drawing

AI summary

Medical instrument includes a substrate, in which cells are in contact with or held on a surface of the substrate, and at least the surface of the substrate which holds the cells is formed of a fluorine-containing cyclic olefin polymer which contains a repeating structure unit represented by Formula (1),wherein in Formula (1), at least one of R1 to R4 is fluorine, an alkyl with 1 to 10 carbon atoms which contains fluorine, an alkoxy with 1 to 10 carbon atoms which contains fluorine, or an alkoxyalkyl with 2 to 10 carbon atoms which contains fluorine, R1 to R4 are selected from hydrogen and certain non-fluorinated groups when R1 to R4 do not contain fluorine, R1 to R4 may be the same as or different from each other, and R1 to R4 may be bonded to each other to form a cyclic structure.