Temperature-Responsive Graft Polymer for Cell Culture and Chromatography

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Solution Overview

Problem

Current cell culture technologies face challenges in efficiently exfoliating adherent cells without enzymatic treatment and in developing chromatographic systems that do not use harmful organic solvents, leading to incomplete separation and potential contamination.

Innovation Solution

A novel graft polymer with a dendritic styrene skeleton and temperature-responsive polymer grafted at its terminal is used to create a substrate for cell culture and chromatographic carrier, allowing for efficient cell exfoliation by temperature change and improved chromatographic separation using a single aqueous mobile phase.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If enzymatic treatment is used to exfoliate adherent cells, then cell separation is achieved, but outer surface proteins are disrupted and cell functionality is compromised

Engineering Contradiction:
Improvecell exfoliation efficiencyVSAvoidcell protein integrity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention changes the physical parameter of temperature to control polymer conformation and surface properties. By adjusting temperature, the polymer substrate transitions between adherent and non-adherent states, enabling cell exfoliation without enzymatic treatment and preserving protein integrity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces enzymatic treatment with a physical temperature-based mechanism. The temperature-responsive polymer substrate uses thermal energy to alter surface properties, substituting the need for enzymes while achieving the same cell separation function.

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

2Measurement precision

If conventional HPLC with organic solvents is used for separation, then substance separation is achieved, but harmful solvents are introduced and physiological activity is impaired

Engineering Contradiction:
Improveseparation resolutionVSAvoidsolvent harm to substances
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention changes the operating parameter from chemical solvent composition to temperature. The temperature-responsive polymer substrate allows separation based on temperature-induced conformational changes, enabling aqueous mobile phase chromatography that avoids harmful organic solvents while maintaining separation resolution.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces chemical separation mechanisms (solvent interactions) with physical mechanisms (temperature-responsive polymer conformation). This substitution allows separation of physiological substances using aqueous mobile phases, eliminating solvent harm while preserving substance functionality.

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

3Reliability

If temperature-responsive polymer is grafted at terminal of dendritic polymer, then cell exfoliation and chromatographic separation are improved, but polymer synthesis complexity increases

Engineering Contradiction:
Improvefunctional performanceVSAvoidpolymer synthesis process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention segments the polymer structure into distinct functional modules: a dendritic polymer backbone providing structural framework and a temperature-responsive polymer graft at the terminal providing functional properties. This segmentation allows independent optimization of each component while simplifying the overall synthesis process.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention applies local quality by concentrating the temperature-responsive functionality at the terminal graft rather than throughout the entire polymer structure. This localized approach maintains simplicity in the bulk polymer synthesis while introducing sophisticated temperature-responsive behavior where needed for cell exfoliation and chromatographic separation.

Inventive Principle:
Principle #3Local quality

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 enables efficient cell exfoliation without enzymatic treatment and effective separation of peptides and proteins across a wide range, maintaining their functionality and avoiding the use of harmful solvents.

Implementation Method 1

a temperature-responsive substrate for cell culture comprising a substrate surface coated with a graft polymer comprising a dendritic polymer with a styrene skeleton and a polymer having temperature response grafted at a terminal thereof

Methodology Applied
Scientific EffectTemperature-responsive polymer conformation change: Shape Memory Polymer

Implementation Method 2

animal cells must be adhered to a certain place before they are cultured ex vivo

Methodology Applied
Scientific EffectAdhesion: Adhesive

Implementation Method 3

a carrier that can be prepared by a simple method and which is suitable for use in liquid chromatography that is carried out by controlling the interactions on a solid surface to separate valuables such as pharmaceuticals, bio-related substances (e.g. proteins, DNA, and glycolipids) and cells

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS11371015B2Graft polymer, temperature-responsive substrate for cell culture using the same and production method therefor, as well as liquid chromatographic carrier having the novel graft polymer immomibilized thereon and liquid chromatographic method using the same
Publication Date: 2022.06.28 DKS CO LTD
  • US11371015B2 patent drawing
  • US11371015B2 patent drawing
  • US11371015B2 patent drawing

AI summary

By using a graft polymer comprising a dendritic polymer with a styrene skeleton and a hydrophilic polymer grafted to a terminal thereof, a temperature-responsive substrate for cell culture having a temperature-responsive surface for cell culture that allows cells to be cultured with high efficiency and which yet allows cultured cells to be exfoliated in a short period of time and with high efficiency by simply changing the temperature of the substrate surface can be prepared conveniently. If this temperature-responsive substrate for cell culture is used, cells obtained from a variety of tissues can be cultured with high efficiency. If this culture method is utilized, cultured cells can be exfoliated intact in a short amount of time with high efficiency. In addition, by using this graft polymer, a wide range of peptides and proteins can also be separated by simply changing the temperature of a chromatographic carrier. This allows for convenient separation procedure and improves the efficiency of separating operations. What is more, the stereoregularity of the dendritic polymer per se may be utilized to enable separation of solutes based on differences in their molecular structures.