Biological Solution Freezing Device with Bottom-Up Nucleation Control
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Solution Overview
Problem
Existing cryopreservation methods face challenges in achieving consistent freezing and thawing of biological materials in small-volume containers, particularly due to issues with natural convection and ice nucleation, which affect the reproducibility and viability of cells.
Innovation Solution
A device and method for unidirectional bottom-up freezing in multiple small-volume containers, utilizing a heat transfer surface and a holder with compressible means to ensure controlled nucleation and ice growth, with the use of a contact promoting material to enhance heat transfer and consistency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional freezing methods are used for small-volume containers, then freezing can be achieved, but freezing consistency and reproducibility deteriorate due to natural convection and uncontrolled nucleation
Solution Approach 1:
The patent applies preliminary action by pre-cooling the bottom surface of the container before introducing the biological solution. This ensures that nucleation occurs at a controlled location (the bottom surface) and at a predetermined time, eliminating the variability associated with uncontrolled nucleation in conventional methods. The pre-cooled surface acts as a nucleation site that triggers freezing in a consistent manner across multiple containers.
Solution Approach 2:
The patent segments the freezing process into distinct phases: (1) pre-cooling of the container bottom, (2) introduction of biological solution, (3) controlled nucleation at the bottom surface, and (4) unidirectional freezing propagation upward. This segmentation allows each phase to be optimized independently, ensuring consistent nucleation and freezing progression while minimizing natural convection effects.
2Manufacturing precision
If fast cooling is applied to enhance nucleation at the bottom, then nucleation control improves, but uncontrolled freezing of the entire sample increases
Solution Approach 1:
The patent applies local quality by creating a localized cold zone only at the bottom surface of the container during the nucleation phase. The cooling is concentrated at the bottom rather than applied uniformly throughout the container, which triggers nucleation at the bottom while preventing excessive cooling of the entire sample. This localized approach ensures controlled nucleation without causing uncontrolled freezing of the bulk solution.
Solution Approach 2:
The patent employs periodic action by applying fast cooling in a controlled time window immediately after solution introduction, then transitioning to a slower, more gradual cooling rate. This periodic cooling strategy allows nucleation to occur rapidly at the bottom surface during the initial fast-cooling phase, followed by controlled freezing propagation during the subsequent slower cooling phase, preventing uncontrolled freezing.
3Manufacturing precision
If unidirectional bottom-up freezing is implemented, then freezing homogeneity improves, but device complexity increases due to additional heat transfer control mechanisms
Solution Approach 1:
The patent uses the container bottom surface as an intermediary element that mediates heat transfer between the cooling system and the biological solution. By pre-cooling this intermediary surface and using it as the nucleation site, the system achieves unidirectional bottom-up freezing without requiring complex active control mechanisms throughout the container. The intermediary bottom surface simplifies the heat transfer control while maintaining freezing homogeneity.
Solution Approach 2:
The patent inverts the conventional freezing approach by initiating freezing at the bottom of the container rather than from the top or sides. This inversion creates a unidirectional freezing front that propagates upward through the solution, improving freezing homogeneity by eliminating natural convection patterns that occur with conventional cooling geometries. The inverted approach simplifies the thermal field control while achieving better freezing consistency.
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 homogeneous and controlled freezing of biological solutions across multiple containers, ensuring high reproducibility and cell viability, even in small volumes, by decoupling nucleation from ice growth and minimizing uncontrolled freezing.
Implementation Method 1
transfers heat from the biological solution to the container
Implementation Method 2
enabling controlled nucleation... such that the freezing of the biological solutions has a bottom-up geometry
Implementation Method 3
pressing means (103) for pressing the holder (102) against the heat transfer surface (101)... placing the container (109) in contact with the heat transfer surface (101)
Implementation Method 4
a holder (102) comprising at least a cavity for a container (109)... wherein the holder is isolating the container with a low heat conductivity material
Data Source
AI summary
The present disclosure provides systems and methods for use in freezing liquid mixtures or suspensions containing sensitive substances, such as biopharmaceutical materials, under sterile conditions and in small-volume containers. The disclosed device enables the control of ice nucleation of the solution minoring the layer of volume that freezes, while controlling the ice growth rate in a bottom up geometry, and comprises a heat transfer surface (101) with means to control temperature, a holder (102) for multiple containers (109), pressing means (103) to press the holder against the heat transfer surface and optionally a contact promoting material. The disclosed method comprises pre-cooling the device to a temperature substantially below the solution nucleation temperature, placing a container into the holder, contacting the container with the heat transfer surface until a fraction of 10% of the total sample volume is frozen; interrupting the contact between the container and the heat transfer surface; contacting the container with the heat transfer surface at a predefined freezing rate, such that the freezing of the biological solution is homogeneous; until all the volume of the solution is frozen.