Polyampholyte Polymer Cryopreservation Reduces Toxicity

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for cellular cryopreservation face challenges with ice crystallization and recrystallization after freeze-thaw cycles, leading to reduced cell viability, and existing cryoprotectants are not universally applicable across various cell types, complicating the storage and transport of frozen human cells, especially in cell-based therapies.

Innovation Solution

A cryopreserving composition comprising a macromolecular polyampholyte polymer, derived from poly(methylvinyl ether-alt-maleic anhydride), is used to preserve a wide range of biological materials, including cells and proteins, by freezing them in a specific concentration of the polymer at cryopreserving temperatures, which enhances cell survival and reduces toxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If organic solvents like DMSO or glycerol are used for cryopreservation, then cell survival is improved, but toxicity increases

Engineering Contradiction:
Improvecell survivalVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameters of the cryoprotectant by using polyampholyte polymers with specific molecular weights (10,000-1,000,000 Da) and charge densities, replacing small molecule organic solvents. This parameter change maintains cryoprotective efficacy while reducing toxicity through the polymer's size and charge characteristics that prevent cellular uptake and metabolic disruption

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses polyampholyte polymers that contain both positive and negative charges within the same molecular structure, creating a composite material with dual functionality. The amphoteric nature allows the polymer to interact with both ice crystals and cell membranes, providing protection while maintaining biocompatibility and reducing toxic effects

Inventive Principle:
Principle #40Composite materials

2Reliability

If ice recrystallization inhibitors are used to maintain cell survival, then cell viability is improved, but the complexity of cryoprotection increases

Engineering Contradiction:
Improvecell viabilityVSAvoidcryoprotection complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The polyampholyte polymer serves multiple functions simultaneously: it acts as an ice recrystallization inhibitor, a cryoprotectant, and a viscosity modifier. This single multi-functional material replaces the need for multiple separate additives, simplifying the cryoprotection formulation while maintaining high cell viability across different cell types

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If different cryoprotectants are used for different cell types, then cell survival is optimized, but the logistics of cell therapies become more complex

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

Solution Approach 1:

The polyampholyte polymer formulation provides universal cryoprotection that works effectively across multiple cell types including red blood cells, white blood cells, platelets, and stem cells. This universality eliminates the need for cell-type-specific protocol development and simplifies logistics in cell therapy manufacturing and transfusion medicine

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

By adjusting the polymer concentration and molecular weight parameters, the same polyampholyte base material can be optimized for different cell types without changing the fundamental cryoprotectant identity. This allows a single platform material to serve multiple applications, reducing logistical complexity while maintaining optimized cell survival

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 polyampholyte polymer achieves red blood cell recovery rates exceeding 80% post-freezing, comparable to glycerol methods, and demonstrates improved cell survival and reduced toxicity across various cell types, simplifying the logistics of cell therapies and transfusion medicine by providing a universal cryoprotectant.

Implementation Method 1

One issue in the field of cellular cryopreservation is ice crystallization and recrystallization after freeze-thaw cycles; this leads to reduced viability of cells. There are a number of ways that have been developed in order to maintain cell survival: these include the use of organic solvents DMSO or glycerol, and the use of ice recrystallization inhibitors (IRIs)

Methodology Applied
Scientific EffectIce recrystallization inhibition:

Implementation Method 2

Cryopreservation is a common method for storing biological material in an inactive state over prolonged periods of time. Processes of using a macromolecular polyampholyte have now been developed which provide red blood cell recovery rates (post-freezing) of over 80%

Methodology Applied
Scientific EffectCryopreservation:

Data Source

PatentUS11998002B2Cryopreserving processes
Publication Date: 2024.06.04 UNIVERSITY OF WARWICK
  • US11998002B2 patent drawing
  • US11998002B2 patent drawing
  • US11998002B2 patent drawing

AI summary

The present invention relates to processes for producing compositions for the cryopreservation of biological materials, e.g. cells and proteins. The compositions comprise a polyampholyte polymer. The invention also provides certain cryopreserving compositions comprising the polyampholyte polymer.