Cell Dissociation Device Using Controlled Shear Stress
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Solution Overview
Problem
Existing mechanical cell dissociation technologies for mammalian cell agglomerations often result in inconsistent cell quality due to manual handling and mechanical forces that negatively impact cell viability, making them unsuitable for cell therapy applications.
Innovation Solution
A method involving a recirculation loop with a shear component that applies a maximal shear of 2-500 Pa to dissociate mammalian cell agglomerations between 30 µm to 300 µm into single cells or oligomers of 8-30 µm, ensuring consistent cell quality and viability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If manual mechanical dissociation (pipetting up-and-down) is used, then cell aggregates can be dissociated, but cell quality becomes inconsistent due to differences between handlers
Solution Approach 1:
The patent replaces manual mechanical pipetting with an automated recirculation system that uses controlled shear stress (2-500 Pa) to dissociate cell aggregates. This substitution eliminates human variability and provides consistent, reproducible dissociation results across different operators while maintaining ease of operation through automated pumping mechanisms.
Solution Approach 2:
The patent defines specific shear stress parameters (2-500 Pa) and recirculation conditions to optimize dissociation. By controlling these physical parameters, the system achieves consistent cell quality regardless of operator skill level, transforming a skill-dependent manual process into a parameter-controlled automated process.
2Productivity
If strong mechanical forces (sonication) are used for dissociation, then dissociation efficiency increases, but cell viability decreases due to negative impact of mechanical forces
Solution Approach 1:
The patent identifies and controls the shear stress parameter within a specific range (2-500 Pa) that is sufficient to dissociate cell aggregates effectively while remaining below the threshold that causes significant cell damage. This optimized parameter range achieves both high dissociation efficiency and maintained cell viability, resolving the contradiction between productivity and harmful effects.
Solution Approach 2:
The recirculation system applies shear stress repeatedly over multiple passes rather than using a single intense mechanical force. This partial action approach gradually dissociates aggregates while allowing cells to recover between passes, achieving complete dissociation without the need for excessive mechanical force that would harm cell viability.
3Productivity
If enzymatic dissociation is used, then cell aggregates can be dissociated, but enzymatic residues remain in the final cell therapy product
Solution Approach 1:
The patent replaces enzymatic dissociation with a purely mechanical recirculation system that uses controlled shear stress to dissociate cell aggregates. This substitution eliminates the need for enzymes entirely, so no enzymatic residues remain in the final cell therapy product, while still achieving effective dissociation through the defined shear stress parameters.
4Loss of substance
If mechanical dissociation is used for cell therapy applications, then enzymatic residues are avoided, but cell quality consistency becomes problematic
Solution Approach 1:
The patent replaces uncontrolled manual mechanical dissociation with a controlled recirculation system that applies defined shear stress (2-500 Pa). This maintains the advantage of avoiding enzymatic residues while achieving consistent cell quality through parameter control and automation, resolving the contradiction between substance purity and manufacturing precision.
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 provides reliable dissociation with minimal cell damage, maintaining cell viability between 70-100% and low cell debris, making it suitable for cell therapy applications.
Implementation Method 1
bringing said mammalian cell agglomeration in the range of between greater than (>)30 μm to 300 μm into contact with a shear component (2) exerting a maximal shear in the range of between 2 Pa and 500 Pa thereby dissociating the mammalian cell agglomeration
Data Source
Figure 1
AI summary
What is described herein relates to a method and a device for dissociating cell agglomerations in the range of between >30 µm to 300 µm after harvest into single cells or cell oligomers in the range of 8-30 µm comprising the steps of • providing cell agglomerations in the range of between >30 µm to 300 µm • passing said cell agglomerations in the range of between >30 µm to 300 µm through a recirculation loop • bringing said cell agglomerations in the range of between >30 µm to 300 µm into contact with a shear component exerting a maximal shear in the range of between 2 Pa and 500 Pa thereby dissociating the cell agglomerations in the range of between >30 µm to 300 µm into single cells or cell oligomers in the range of 8-30 µm.