Hydrogel Encapsulated Ice Nucleation for Cryopreservation

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Solution Overview

Problem

Current methods for controlling ice nucleation in cryopreservation lack consistency and standardization, particularly in large-scale biological sample preservation, and introduce biocompatibility and toxicity concerns due to direct contact with foreign ice nuclei.

Innovation Solution

Development of hydrogel particles encapsulating ice nucleating agents like SNOMAX or silver iodide, which can be tuned for specific ice nucleation temperatures, reducing the range of nucleation temperatures and minimizing direct contact with biological samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If foreign ice nuclei are used to control ice nucleation, then ice nucleation temperature can be raised, but biocompatibility and toxicity concerns arise due to direct contact with biological samples

Engineering Contradiction:
Improveice nucleation temperatureVSAvoidbiocompatibility and toxicity
Core Design Contradiction:
TemperatureVSObject-affected harmful factors

Solution Approach 1:

The patent introduces hydrogel particles as intermediary carriers that encapsulate ice nucleating agents. These particles serve as a mediator between the ice nucleating agent and the biological sample, allowing the agent to function while being physically separated from direct contact with the biological material. The hydrogel matrix protects the biological samples from toxic effects while still enabling ice nucleation through the encapsulated agents.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The ice nucleating agents are nested within the hydrogel particles, creating a hierarchical structure where the agent is contained inside the carrier matrix. This nesting arrangement allows the ice nucleating agent to be present in the system without direct exposure to biological samples, resolving the contradiction between functional effectiveness and biocompatibility.

Inventive Principle:
Principle #7Nested doll (Nesting)

2Reliability

If conventional ice nucleation methods are used, then ice nucleation can be initiated, but lack of consistency and standardization occurs in large-scale biological sample preservation

Engineering Contradiction:
Improveconsistency and standardizationVSAvoidlarge-scale preservation capability
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent standardizes ice nucleation by controlling parameters of the hydrogel particles such as size, composition, and ice nucleating agent concentration. By adjusting these parameters, the ice nucleation temperature and timing can be precisely controlled and replicated across different samples, achieving consistency and standardization in large-scale preservation operations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The hydrogel particles provide localized control of ice nucleation properties within each particle, allowing for uniform distribution of ice nucleating agents throughout the biological sample. This local quality approach ensures consistent nucleation behavior across multiple samples, improving reliability for large-scale applications.

Inventive Principle:
Principle #3Local quality

3Temperature

If ice nucleation is delayed until homogeneous nucleation occurs, then supercooling is maximized, but intracellular ice formation probability increases

Engineering Contradiction:
Improvesupercooling degreeVSAvoidintracellular ice formation
Core Design Contradiction:
TemperatureVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by introducing ice nucleating agents before cooling begins, which initiate ice formation at controlled temperatures. This preliminary initiation prevents the system from reaching deep supercooling states that would lead to uncontrolled intracellular ice formation. The agents are prepared in advance within hydrogel particles and released at the appropriate moment during cooling.

Inventive Principle:
Principle #10Preliminary action

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 use of hydrogel particles with encapsulated ice nucleating agents provides predictable and controlled ice nucleation, enhancing the viability of biological samples by reducing intracellular ice formation and minimizing ischemia-reperfusion damage during cryopreservation.

Implementation Method 1

Without external nuclei, water and aqueous solutions will maintain a supercooled liquid state well below the melting point until homogeneous ice nucleation occurs. However, the initiation of ice nucleation at a relatively higher subzero temperature offers many benefits

Methodology Applied
Scientific EffectHeterogeneous nucleation: Nucleation

Implementation Method 2

the difference between the ice nucleation temperature and the melting point, and initiate ice nucleation at relatively high subzero temperatures

Methodology Applied
Scientific EffectSupercooling: Supercooling

Implementation Method 3

The ice nucleating agent can be SNOMAX or silver iodide. The ice nucleating agent can also be a protein, a carbohydrate, or a phospholipid

Methodology Applied
Scientific EffectCatalysis: Catalysis

Implementation Method 4

hydrogel particles containing an ice nucleating agent, wherein the ice nucleating agent is enclosed within the hydrogel particles

Methodology Applied
Scientific EffectPhysical containment: Physical Containment

Implementation Method 5

the hydrogel particle can further include a cryoprotectant (e.g., DMSO, EG, PROH, 3-OMG, or glycerol)

Methodology Applied
Scientific EffectFreezing point depression: Freezing

Data Source

PatentUS20230371499A1Ice Nucleation Formulations for Cryopreservation and Stabilization of Biologics
Publication Date: 2023.11.23 THE GENERAL HOSPITAL CORP
  • US20230371499A1 patent drawing
  • US20230371499A1 patent drawing
  • US20230371499A1 patent drawing

AI summary

This disclosure relates to ice nucleation formulations for cryopreservation and stabilization of biologics, and methods of use thereof.