Block Copolymer for Rapid Cell Detachment

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Solution Overview

Problem

Current methods for cell separation from culture substrates using temperature-responsive polymers require prolonged cooling times, which can damage cells and reduce their activity, necessitating a more efficient approach for cell detachment without proteolytic enzymes.

Innovation Solution

A block copolymer comprising a temperature-responsive polymer, a hydrophilic polymer, and a hydrophobic polymer is used to form a membrane on the substrate, allowing for rapid cell separation by temperature reduction, promoting hydrophilization of the substrate surface and shortening the cooling time needed for cell detachment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If temperature-responsive polymer is used for cell separation, then cell detachment can be achieved without proteolytic enzymes, but cooling time is prolonged which reduces cell activity

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

Solution Approach 1:

The patent modifies the polymer structure by incorporating hydrophilic groups (HEMA, NVP) to change the thermal response characteristics of the temperature-responsive polymer, enabling faster phase transition and reduced cooling time while maintaining cell integrity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite polymer system combining temperature-responsive polymer chains with hydrophilic polymer segments, achieving both effective cell detachment and rapid response time through synergistic material properties

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If conventional temperature-responsive polymers are used, then cell detachment is achieved, but the cooling process takes too long affecting cell viability

Engineering Contradiction:
Improvecell detachment methodVSAvoidcooling time
Core Design Contradiction:
Ease of operationVSLoss of time

Solution Approach 1:

The patent changes the thermal transition parameters of the polymer by introducing hydrophilic monomers with specific glass transition temperatures and hydrogen bonding capabilities, enabling faster water reorganization and reduced cooling duration

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes and optimizes the phase transition behavior of the polymer at its lower critical solution temperature, where the polymer undergoes sol-gel transition that rapidly expels water and detaches cells within minutes rather than hours

Inventive Principle:
Principle #36Phase transitions

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 block copolymer enables efficient cell separation in a short time without damaging the cells, even after cell culture, by altering the substrate's surface properties in response to temperature changes, facilitating cell detachment without the use of proteolytic enzymes.

Implementation Method 1

the adhesiveness of the substrate surface is weakened by the sol transition of the temperature-responsive polymer due to a reduction in temperature of the surrounding environment

Methodology Applied
Scientific EffectSol transition: Phase Change

Implementation Method 2

allowing for rapid cell separation by temperature reduction, promoting hydrophilization of the substrate surface

Methodology Applied
Scientific EffectHydrophilization: Wetting

Data Source

PatentEP3495400B1Block copolymer and surface treatment agent using same
Publication Date: 2024.08.28 TOSOH CORP
  • EP3495400B1 patent drawing
  • EP3495400B1 patent drawing
  • EP3495400B1 patent drawing

AI summary

The present invention addresses the problem of providing a block copolymer which is useful as a surface treatment agent for cell culture substrates, said surface treatment agent enabling cell separation in a short period of time. The above-mentioned problem is solved by a block copolymer that comprises the following blocks (A), (B) and (C). (A) a temperature-responsive polymer block that has a lower critical solution temperature (LCST) within the range of from 0°C to 50°C with respect to water (B) a hydrophilic polymer block that does not have an LCST within the range of from 0°C to 50°C, while having an HLB value (as determined by a Griffin method) within the range of from 9 (inclusive) to 20 (exclusive) (C) a hydrophobic polymer block that does not have an LCST within the range of from 0°C to 50°C, while having an HLB value (as determined by a Griffin method) within the range of from 0 (inclusive) to 9 (exclusive)