Temperature-Responsive Substrate with Fluorine Polymer for Cell Detachment

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Solution Overview

Problem

Conventional temperature-responsive polymer-coated cell culture substrates face challenges in uniform cell attachment and detachment, with cell sheets often breaking during detachment due to the sea-island structure of the polymer coatings, leading to damage and contamination issues.

Innovation Solution

A temperature-responsive substrate with a fluorine-containing monomer-derived unit is developed, featuring a lower critical solution temperature (LCST) of 0 to 15°C, achieved through radiation surface graft polymerization, which enhances cell detachment with reduced damage and contamination, and allows for easier handling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional temperature-responsive polymer coatings are used, then cell detachment function is provided, but cell sheets break during detachment due to non-uniform structure

Engineering Contradiction:
Improvecell sheet integrityVSAvoidcoating uniformity
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies homogeneity by ensuring uniform distribution of temperature-responsive polymer chains throughout the coating layer. The coating is designed so that polymer chains are evenly dispersed at the molecular level, eliminating the sea-island structure. This uniform distribution ensures consistent cell detachment properties across the entire substrate surface, preventing cell sheet breakage during detachment while maintaining reliable temperature-responsive functionality.

Inventive Principle:
Principle #33Homogeneity

2Ease of operation

If enzyme treatments or chemical treatments are used for cell detachment, then cells can be detached from substrate, but contamination risk increases and cell natural functions are impaired

Engineering Contradiction:
Improvecell detachment easeVSAvoidcontamination and cell damage
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent replaces chemical/enzymatic treatment systems with a physical temperature-responsive system. The coating contains polymer chains that undergo conformational changes in response to temperature variations. At physiological temperature, the chains maintain a state that promotes cell attachment, while at a slightly lower temperature, the chains transition to a state that reduces adhesion, enabling effortless cell detachment. This mechanical/physical approach eliminates the need for harmful chemicals and enzymes, thereby reducing contamination risk and preserving cell natural functions.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If temperature-responsive polymer coating is applied, then cell detachment is enabled, but grafting does not progress uniformly in crystal portions leading to non-uniform cell attachment

Engineering Contradiction:
Improvecell attachment uniformityVSAvoidgrafting uniformity
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by carefully controlling the molecular weight, composition, and density of the temperature-responsive polymer chains in the coating. These parameter adjustments ensure that the polymer chains remain in a flexible, non-crystalline state that allows uniform grafting across the entire substrate surface. The modified polymer parameters enable consistent interaction with cells throughout the coating layer, resulting in uniform cell attachment and growth while maintaining temperature-responsive detachment functionality.

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 substrate improves cell detachment efficiency, reduces damage to cell sheets, and facilitates easier handling by controlling detachment at lower temperatures, ensuring uniform cell growth and minimizing contamination risks.

Implementation Method 1

a temperature-responsive substrate having on its surface a layer comprising at least one polymer, wherein the at least one polymer is responsive to temperature and comprises a fluorine-containing monomer-derived unit

Methodology Applied
Scientific EffectLower critical solution temperature (LCST): Phase Change

Implementation Method 2

achieved through radiation surface graft polymerization

Methodology Applied
Scientific EffectPhotopolymerization: Photopolymerisation

Data Source

PatentUS10689615B2Temperature-responsive base material, method for producing same, and method for evaluating same
Publication Date: 2020.06.23 DAIKIN INDUSTRIES LTD
  • US10689615B2 patent drawing
  • US10689615B2 patent drawing
  • US10689615B2 patent drawing

AI summary

A temperature-responsive substrate having on its surface a layer containing at least one polymer, the at least one polymer being responsive to temperature and containing a fluorine-containing monomer-derived unit. Also disclosed is a polymer and composition for use in producing the substrate, as well as methods for producing, using and evaluating the substrate.