Reversible Cryopreservation Under Pressure to Limit Ice Cracking
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Solution Overview
Problem
Current cryopreservation methods often result in suboptimal outcomes for multicellular biological constructs, leading to damage from ice formation and limiting the viability of preserved tissues, which hinders advancements in research and clinical applications.
Innovation Solution
A method involving the loading of cryoprotective agents into biological specimens, controlled cooling and rewarming at specific rates and pressures to prevent ice formation, combined with the use of nanoparticles and volumetric warming to enhance uniformity and reduce cracking, along with the use of a system that includes a container for controlled pressure and thermal contact to facilitate cryopreservation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If cryopreservation is performed using conventional methods, then long-term preservation is achieved, but ice formation damages the biological construct
Solution Approach 1:
The patent changes the physical parameters of the preservation system by applying high pressure (e.g., 100-500 MPa) during cooling to suppress ice crystal formation. This pressure parameter modification allows the system to achieve both long-term preservation and avoid ice damage by altering the phase behavior of water in the biological construct.
Solution Approach 2:
The patent utilizes controlled phase transitions by cooling the biological construct under high pressure to achieve vitrification (transition to glassy state) rather than crystalline ice formation. The pressure-induced phase transition prevents harmful ice crystal formation while enabling long-term stable preservation at cryogenic temperatures.
2Object-affected harmful factors
If cooling rate is increased to prevent ice formation, then ice damage is reduced, but thermal stress and cracking increase
Solution Approach 1:
The patent modifies the pressure parameter during cooling to enable slower cooling rates without ice formation. The high pressure environment changes the freezing point and ice formation kinetics, allowing gradual cooling that prevents both ice damage and thermal stress cracking by maintaining structural integrity throughout the process.
3Object-affected harmful factors
If high pressure is applied to prevent ice expansion, then ice expansion damage is reduced, but device complexity increases
Solution Approach 1:
The patent applies high pressure before and during the cooling process to prevent ice expansion damage before it can occur. By establishing the pressure condition in advance, the system eliminates the need for complex real-time pressure adjustment mechanisms during freezing, thereby reducing overall device complexity while still protecting against ice expansion.
4Strength
If homogeneous cooling is used to reduce cracking, then structural integrity is maintained, but cooling time increases
Solution Approach 1:
The patent changes the pressure parameter to enable faster cooling rates while maintaining homogeneous temperature distribution. The high pressure environment alters heat transfer characteristics and reduces thermal gradients, allowing rapid cooling without the development of cracking-prone stress concentrations, thus achieving both speed and structural integrity.
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 method achieves high viability preservation of biological specimens by minimizing ice formation and cracking, enabling effective long-term storage and rapid restoration of tissues for research and clinical applications.
Implementation Method 1
One approach to cryopreservation is vitrification, where biological constructs are cooled to cryogenic temperatures without the formation of ice.
Implementation Method 2
The cooling in (b) can be performed (i) at a first rate to reduce ice formation
Implementation Method 3
cooling the biological specimen (b) substantially homogeneously to reduce propensity for cracking of the preserved biological specimen
Implementation Method 4
cooling the biological specimen (b) at a first pressure to prevent or reduce ice expansion within the preserved biological specimen
Implementation Method 5
rewarming the biological specimen by increasing a temperature of the biological specimen above the preservation temperature state
Implementation Method 6
The rewarming in (d) can be performed (i) at a second rate to reduce ice formation
Implementation Method 7
The rewarming in (d) can be performed (ii) substantially homogeneously to reduce propensity for cracking
Implementation Method 8
The rewarming in (d) can be performed (iii) at a second pressure to prevent or reduce ice expansion
Data Source
AI summary
Provided herein are systems, methods, and cryoprotective solutions for reversible cryopreservation of biological specimens, whole organs, and whole organisms. Exemplary methods include loading a cryoprotective agent into the biological specimen, cooling the biological specimen to a cryogenic temperature for preservation, storing the biological specimen at a preservation temperature state to preserve the biological specimen, rewarming the biological specimen by increasing a temperature of the biological specimen above the preservation temperature state, and unloading the cryoprotective agent from the biological specimen. The cooling is performed at a first rate to reduce ice formation, substantially homogeneously to reduce propensity for cracking of the preserved biological specimen, and at a first pressure to prevent or reduce ice expansion within the preserved biological specimen. The rewarming is performed at a second rate to reduce ice formation, substantially homogeneously to reduce propensity for cracking, and at a second pressure to prevent or reduce ice expansion.