Cryopreservation Apparatus Movable Support Cooling Tubes

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Solution Overview

Problem

Conventional apparatuses for cryopreserving cellular samples face challenges in achieving simultaneous and reproducible freezing due to inhomogeneous temperature distribution and unsuitable seeding functions, leading to variations in cooling rates and product quality.

Innovation Solution

An apparatus with a movable support system that engages vials with cooling tubes at a predetermined height, ensuring controlled and synchronized crystallization, and a cooling device with a ring-shaped tube portion for efficient refrigerant distribution, allowing for precise temperature control and uniform cooling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional apparatuses cool multiple vials simultaneously in a cubic cooling chamber, then productivity is improved by processing multiple samples at once, but manufacturing precision deteriorates due to inhomogeneous temperature distribution and varying cooling rates

Engineering Contradiction:
Improvenumber of samples processed simultaneouslyVSAvoidtemperature distribution uniformity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The cooling chamber is divided into multiple cooling zones, each with independent temperature control and separate cooling circuits. This segmentation allows each zone to maintain uniform temperature distribution while processing multiple vials simultaneously across different zones, resolving the contradiction between high productivity and temperature uniformity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the cooling chamber are equipped with tailored cooling characteristics to match the specific thermal requirements of vials in different positions. The apparatus applies localized temperature control strategies, ensuring that each spatial location achieves the required cooling rate and temperature uniformity, thereby maintaining manufacturing precision across all samples processed in parallel.

Inventive Principle:
Principle #3Local quality

2Device complexity

If conventional apparatuses use fixed cooling chambers, then device complexity is reduced, but manufacturing precision deteriorates due to inability to control seeding and cooling rates precisely

Engineering Contradiction:
Improvecooling chamber structureVSAvoidcooling rate control
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The cooling apparatus transitions from fixed static cooling chambers to dynamic adjustable cooling zones with movable cooling elements and variable flow rate circuits. This allows real-time adjustment of cooling rates and seeding conditions for each zone, achieving precise manufacturing precision while accepting increased device complexity as a necessary trade-off.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The apparatus enables independent adjustment of multiple parameters including cooling rate, seeding temperature, and refrigerant flow rate for each cooling zone. By implementing variable parameter control rather than fixed conditions, the system achieves precise control over crystallization processes, resolving the contradiction between simple device structure and precise manufacturing control.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If cooling rate is increased to prevent solution effects and osmosis damage, then reliability of cell viability is improved, but object-generated harmful factors worsen due to intracellular ice formation

Engineering Contradiction:
Improvecell viabilityVSAvoidintracellular ice formation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The apparatus applies preliminary controlled seeding at a specific temperature before the main cooling phase. By inducing ice crystal formation at a controlled moment and temperature, the system prepares the extracellular environment in advance, enabling subsequent rapid cooling without intracellular ice formation. This preliminary action ensures cell viability while avoiding the harmful effects of uncontrolled freezing.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The cooling process rapidly transitions through the critical temperature range where intracellular freezing could occur, after preliminary seeding has established controlled extracellular ice formation. By rushing through the dangerous temperature zone quickly, the apparatus prevents intracellular ice formation while maintaining high cooling rates that protect cell viability, thus resolving the contradiction between reliability and harmful factors.

Inventive Principle:
Principle #21Skipping (Rushing through)

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

Enables reproducible and simultaneous freezing of cellular samples with controlled crystallization, minimizing damage from excessive cooling rates and ensuring consistent product quality across multiple samples.

Implementation Method 1

a cooling device (104) comprising means configured to cool an interior of the cooling chamber (102), wherein the cooling device (104) further comprises cooling tubes (146) that are separate from the means configured to cool the interior of the cooling chamber (102) and that are arranged within the cooling chamber (102)

Methodology Applied
Scientific EffectHeat removal: Conduction (thermal)

Implementation Method 2

The formation of the first ice crystal, called "seeding," in the super-cooled solution occurs either spontaneous over a range of temperatures or by means of selective induction, e.g. by a cold pulse or mechanically by rocking at a specific temperature

Methodology Applied
Scientific EffectPhase change: Phase Change

Implementation Method 3

Due to the phase change from liquid to solid during seeding, crystallization enthalpy ("latent heat") is set free which causes a temperature rise in the sub-cooled medium up to the freezing point

Methodology Applied
Scientific EffectLatent heat: Latent Heat

Implementation Method 4

Super-cooling is defined as a lowering of the temperature of a liquid below its freezing point without the liquid freezing or solidifying

Methodology Applied
Scientific EffectSuper-cooling: Supercooling

Implementation Method 5

an induction of seeding is desirable to avoid extensive super-cooling and allow simultaneous crystallization of all samples

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Data Source

PatentUS10674720B2Apparatus for cryopreserving a plurality of cellular samples and method for cryopreserving a plurality of cellular samples
Publication Date: 2020.06.09 F HOFFMANN LA ROCHE INC
  • US10674720B2 patent drawing
  • US10674720B2 patent drawing
  • US10674720B2 patent drawing

AI summary

An apparatus and a method for cryopreserving a plurality of cellular samples are disclosed. The apparatus may include a cooling chamber and a cooling device that may include a mechanism to cool an interior of the cooling chamber. The cooling device may further include cooling tubes that are separate from the mechanism to cool the interior of the cooling chamber and that are arranged within the cooling chamber. The cooling device may provide a flow of refrigerant through the cooling tubes and a support for supporting a plurality of vials for storing cellular samples. The support may be movable relative to the cooling tubes such that the plurality of vials may be engageable with the cooling tubes.