Process and device for temperature and pressure controlled cryopreservation
Inventors
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Assignees
University of California San Diego UCSD
University of California, San Diego (UCSD)The University of California, San Diego (UCSD) is a leading public research university located in La Jolla, California. Known for its innovative and interdisciplinary approach, UCSD offers a wide range of undergraduate, graduate, and professional programs across various fields. The university is committed to fostering a diverse and inclusive community, promoting sustainability, and driving social mobility through education, research, and public service. UCSD is recognized for its contributions to research and innovation, particularly in areas such as climate science, health innovation, and artificial intelligence.
The University of California, San Diego (UCSD) is a leading public research university located in La Jolla, California. Known for its innovative and interdisciplinary approach, UCSD offers a wide range of undergraduate, graduate, and professional programs across various fields. The university is committed to fostering a diverse and inclusive community, promoting sustainability, and driving social mobility through education, research, and public service. UCSD is recognized for its contributions to research and innovation, particularly in areas such as climate science, health innovation, and artificial intelligence.
Publication Number
US-12349672-B2
Publication Date
2025-07-08
Expiration Date
2038-08-09
Abstract
The disclosure provides processes for temperature and pressure controlled cryopreservation of samples by using isochoric systems.
Core Innovation
The invention provides processes and systems for cryopreservation of biological samples using isochoric (constant volume) systems equipped to monitor and control both temperature and pressure. Unlike conventional cryopreservation methods that assume constant pressure and volume, this invention emphasizes that pressure and volume can change and are critical for defining the thermodynamic state during freezing and thawing. The system measures pressure and temperature simultaneously to gain precise insight into the thermodynamics of ice formation and vitrification states.
The disclosed methods include cooling a biological sample in a controlled manner through multiple temperature stages, maintaining thermodynamic equilibrium at each stage for both pressure and temperature. The system uses an isochoric chamber with rigid walls and integrates a pressure transducer and thermometer connected to a computer to control heating and cooling cycles. This approach enables monitoring pressure changes that indicate ice crystal formation or vitrification, allowing control of the cryopreservation process to promote vitrification and prevent freezing damage.
The problem addressed by the invention is that current cryopreservation protocols insufficiently account for pressure and volume changes, relying largely on temperature monitoring alone. Because cryopreservation is a thermodynamic process defined by temperature, pressure, volume, and composition, not measuring or controlling pressure and volume reduces protocol repeatability and control. This limitation is especially critical for cryopreservation of large biological samples like organs, where precise control is needed to ensure preservation success.
Claims Coverage
The claims of the patent cover a system and methods for preserving biological materials at sub-freezing temperatures using an isochoric chamber with pressure monitoring and temperature control, describing the main inventive features of pressure-based control to promote vitrification.
Isochoric chamber with pressure-based temperature control to promote vitrification
A system comprising an isochoric chamber, a pressure transducer measuring pressure within the chamber, a heating/cooling system thermally coupled to the chamber, and a computer that controls cooling/heating rates to maintain constant pressure to promote vitrification under thermodynamic equilibrium. The computer operates by cooling the sample incrementally, holding at each temperature for equilibrium, repeating this for multiple temperatures to reach subfreezing temperatures of −20°C or lower, and controlling heating/cooling based only on pressure measurement.
Pressure-based dynamic adjustment of cooling and warming
Computer instructions to cool or warm the isochoric chamber, measure pressure only, and adjust or inhibit cooling/warming when the pressure changes by a predetermined amount indicating ice crystal formation.
Holding cooling or heating until pressure equilibrium is reached
Upon pressure change indicative of ice formation, the computer holds cooling or heating until thermodynamic equilibrium in terms of pressure is achieved.
Stable pressure holding for isochoric vitrification
The system maintains a stable pressure conducive to isochoric vitrification.
Rigid isochoric chamber capable of withstanding high pressures
An isochoric chamber with rigid walls maintaining constant volume for pressures from atmospheric pressure up to 2500 bar.
Cryopreservation method employing pressure transducer in constant volume chamber
A method for preservation in vitrification processes using a pressure transducer attached to a closed or constant volume chamber to monitor and control the preservation of biological materials.
Cryopreservation of various biological materials
Methods covering preservation of diverse biological materials including biomolecules, cell components, cells, viruses, embryos, tissues, organs, whole organisms, male and female reproductive cells, prokaryotic and eukaryotic organisms.
The claims collectively cover a system and method for temperature and pressure controlled cryopreservation using an isochoric chamber with real-time pressure monitoring and computer-controlled cooling/heating to enable vitrification by detecting and responding to pressure changes that signify ice formation, applicable to a broad range of biological samples.
Stated Advantages
Provides precise insight into the thermodynamic state of ice by monitoring both pressure and temperature during freezing and thawing.
Enables reliable design, optimization, and control of cryopreservation protocols, especially for vitrification, by incorporating pressure measurements.
Pressure measurement serves as a simple and accessible indicator to detect ice crystal formation, vitrification, and devitrification.
Ensures thermodynamic accuracy for repeatable and controllable cryopreservation processes, particularly important for large biological samples like organs.
Pressure is a hydrostatic variable providing comprehensive data throughout the system volume, enhancing monitoring compared to temperature alone.
Documented Applications
Cryopreservation of biological samples including biomolecules, cell components, cells, viruses, embryos, tissues, organs, and whole organisms.
Design and control of cryopreservation protocols to promote vitrification and prevent ice crystal formation.
Assessment of cryoprotectants' effectiveness in preventing ice formation during vitrification and devitrification processes.
Preservation of reproductive cells (male or female), embryos (including human embryos), and organisms (prokaryotic and eukaryotic).
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