Temperature-Responsive Cell Culture Substrate with Patterned Grafting

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Solution Overview

Problem

Conventional temperature-responsive cell culture substrates require multiple steps for grafting temperature-responsive polymers, leading to inefficient production and limitations in designing cell sheets with specific shapes and sizes for grafting onto affected areas.

Innovation Solution

A novel temperature-responsive cell culture substrate is developed with a surface patterned by electron beam irradiation, featuring regions with varying graft densities of temperature-responsive polymers, allowing cells to adhere and detach by temperature change, and inhibiting adhesion in specific areas, using materials like polystyrene and polymethylpentene for efficient cell sheet formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the entire surface of the cell culture substrate is uniformly coated with a temperature-responsive polymer, then the substrate provides consistent cell adhesion and detachment properties, but the size and shape of the resulting cell sheet always depend on the size of the culture substrate, limiting efficient arrangement on affected areas

Engineering Contradiction:
Improvecell adhesion consistencyVSAvoidcell sheet shape control
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The substrate surface is divided into regions with different temperature-responsive polymer coating densities. The first region has a polymer density that allows cell adhesion and detachment by temperature change, while the second region has a higher polymer density that prevents cell adhesion. This local variation in coating density enables precise control of cell sheet shape and size independent of the overall substrate size.

Inventive Principle:
Principle #3Local quality

2Manufacturing precision

If conventional coating methods are used to create patterned regions on the substrate surface, then specific affinity and stimulation-responsive polymer regions can be formed, but the production process requires at least two steps, making it inefficient and complex

Engineering Contradiction:
Improvepatterned region formationVSAvoidproduction process steps
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent combines multiple functions into a single coating step. By applying a temperature-responsive polymer solution to the entire substrate surface and using controlled degradation or selective removal processes, both the cell-adhering regions and cell-nonadhering regions are formed in one production process, eliminating the need for separate coating steps for different regions.

Inventive Principle:
Principle #5Merging (Combining)

3Manufacturing precision

If the graft density of temperature-responsive polymer is increased to prevent cell adhesion in specific areas, then cell sheet shape control is improved, but the production process becomes more complex requiring multiple grafting steps

Engineering Contradiction:
Improvecell sheet shape controlVSAvoidproduction efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent controls cell adhesion properties by varying the density parameter of the temperature-responsive polymer coating across different regions of the substrate. By adjusting the polymer concentration, coating conditions, or using selective degradation approaches, regions with different adhesion characteristics are created in a single process, maintaining high productivity while achieving precise shape control.

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

Enables the production of cell sheets with desired shapes and sizes by varying the graft density of temperature-responsive polymers on a single substrate, simplifying the production process and improving cell culture technology.

Implementation Method 1

a temperature-responsive polymer that varies its interaction with water in a temperature range of 0 to 80°C

Methodology Applied
Scientific EffectPhase change: Phase Change

Implementation Method 2

a surface having a pattern formed by two or more materials exhibiting different grafting efficiencies for the temperature-responsive polymer by electron beam irradiation under the same conditions

Methodology Applied
Scientific EffectElectron beam irradiation: Electron Beam

Data Source

PatentEP2348099B1Temperature-responsive cell culture substrate and method for producing the same
Publication Date: 2017.07.05 CELLSEED
  • EP2348099B1 patent drawingFigure 1
  • EP2348099B1 patent drawingFigure 2
  • EP2348099B1 patent drawingFigure 3~4

AI summary

A substrate having a pattern of two or more materials exhibiting different grafting efficiencies for a temperature-responsive polymer that varies its interaction with water in a temperature range of 0 to 80°C by electron beam irradiation under the same conditions is grafted with the temperature-responsive polymer by simultaneously irradiating the surfaces of the materials with electron beams to obtain a temperature-responsive cell culture substrate. According to this method, a temperature-responsive cell culture substrate having a surface (1) that allows cells to adhere thereto and to grow thereon during cell culturing and that allows the adhering and grown cells to be detached therefrom by changing the culturing temperature and a surface (2) that does not allow the cells to adhere thereto at all can be obtained by a simple process.