Cryobag Thawing with Segmented Heater Banks
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Solution Overview
Problem
Current methods for thawing cryogenically preserved cells in bag-format storage vessels, such as cryobags, are inconsistent and prone to over-thawing, leading to cell damage due to temperature gradients and exposure to toxic cryoprotectants, especially when manual techniques are used and water baths are employed.
Innovation Solution
A system with multiple sensors and heater banks is used to monitor and control the thawing process, ensuring consistent temperature distribution across different bag sizes by dynamically adjusting heating based on sensor feedback, allowing for precise control to maintain a solid phase remnant in the sample, thus preventing over-thawing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If a rapid slew rate in sample vessel temperature is achieved by partial submersion in a water bath set to approximately 37°C, then the thawing speed is improved, but temperature gradients within the vessel are created with highest temperatures at the vessel wall, leading to transient thermodynamic states where temperature exceeds melting temperature even though frozen material is present
Solution Approach 1:
The heating system is divided into multiple independently controllable heater banks positioned at different locations within the water bath. This segmentation allows differential heating control - higher temperatures at the center where frozen material persists and lower temperatures at the walls where thawing is complete, eliminating temperature gradients and preventing overheating while maintaining rapid overall thawing speed.
2Speed
If the temperature of the water bath is increased to achieve faster thawing, then the thawing rate is improved, but the intra-vessel temperature gradient increases, placing an upper limit on the bath temperature
Solution Approach 1:
Different regions of the water bath are assigned different temperature qualities - the center region maintains higher temperatures to rapidly thaw frozen material, while the wall regions operate at lower temperatures to prevent gradient formation. This local quality differentiation allows the system to achieve fast overall thawing rates without creating harmful temperature gradients that would limit bath temperature increases.
3Reliability
If common cryoprotectants are used during thawing, then cell protection during freezing is achieved, but the toxic influence on cells is enhanced at elevated temperatures, requiring lower liquid temperature during thawing
Solution Approach 1:
The water bath temperature is dynamically adjusted during the thawing process rather than maintained at a constant high temperature. The system starts with higher temperatures to rapidly thaw frozen material, then progressively reduces temperature as thawing completes. This dynamic temperature control minimizes the duration of high-temperature exposure to toxic cryoprotectants while still achieving fast thawing, thereby protecting cell viability.
4Ease of operation
If manual thawing techniques are used with water baths, then the process is simple to operate, but the thawing is inconsistent and prone to over-thawing, leading to cell damage
Solution Approach 1:
Temperature sensors continuously monitor the water bath temperature and provide feedback to the control system. Based on this feedback, the controller automatically adjusts the power supplied to each heater bank to maintain precise temperature setpoints. This closed-loop feedback control ensures consistent, repeatable thawing results and prevents over-thawing, eliminating the inconsistency associated with manual techniques while retaining ease of operation through automation.
5Adaptability or versatility
If multiple bag-format storage vessel sizes are thawed, then versatility is improved, but maintaining consistent temperature distribution across different bag sizes becomes difficult
Solution Approach 1:
The heating system dynamically adapts to different bag sizes through independent control of multiple heater banks. Smaller bags receive concentrated heating from nearby heater banks, while larger bags engage multiple heater banks to distribute heat uniformly across their greater volume. This dynamic adjustment of heating patterns based on bag size ensures consistent temperature distribution and prevents both under-thawing and over-thawing across the full range of vessel sizes.
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
This approach enables consistent and repeatable thawing of frozen samples, minimizing cell damage by maintaining a uniform temperature distribution and reducing exposure to high temperatures, thereby improving the viability of thawed cells across various cryobag sizes.
Implementation Method 1
heating the frozen sample using a first heater bank and concurrently heating the frozen sample using a second heater bank
Implementation Method 2
heating the partially thawed sample using the first heater bank
Implementation Method 3
During the transition from the cryogenic storage temperature to the conclusion of the phase change to a completely liquid state
Implementation Method 4
The solid contents of the sample storage vessels contain large islands of crystallized water
Data Source
AI summary
A consistent and repeatable thawing method of frozen samples in a bag-format storage vessel is described herein. Methods and systems may allow for multiple bag-format storage vessel sizes to be used in the same device. A subset of a plurality of sensors may be qualified for the thawing method. The method may further include heating a frozen sample using a first heater bank and a second heater bank. In addition, the method may include measuring a plurality of second temperatures of the bag-format vessel. At or slightly after a second threshold temperature, the method may include heating using the first heater bank and terminating heating using the second heater bank. The method may include terminating the heating of the partially thawed sample using the first heater bank after the partially thawed sample has been heated using the first heater bank for a duration.