Cell Selection via Micro Flow Passage Shear Stress
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Solution Overview
Problem
Conventional methods for selecting cells for perfusion culture, which require high cell density and oxygen supply, often result in cell damage due to fluid stress, as they evaluate cell viability based on antibody production rather than damage resistance, leading to potential cell death.
Innovation Solution
A method involving introducing cells into a micro flow passage to evaluate their damage resistance by measuring stress-induced viability and lactate dehydrogenase release rates, using multiple micro flow passages with precise dimensions to assess shear stress and energy dissipation, allowing for the selection of cells with high damage resistance for perfusion culture.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If cells are selected based on antibody production amount, then productivity is improved, but cell damage resistance deteriorates
Solution Approach 1:
The patent applies preliminary action by evaluating cell damage resistance through micro flow passage testing before selecting clones for perfusion culture. This preliminary evaluation identifies clones with high damage resistance, ensuring they can withstand the harsh conditions of perfusion culture while maintaining high productivity.
Solution Approach 2:
The patent changes the selection parameter from solely antibody production amount to a combination of antibody production and damage resistance evaluation. By introducing damage resistance as a new selection parameter through micro flow passage testing, the method identifies clones that satisfy both productivity and reliability requirements.
2Productivity
If high cell density perfusion culture is implemented, then productivity is improved, but cell damage increases
Solution Approach 1:
The patent applies preliminary action by pre-evaluating clone damage resistance using micro flow passages before initiating perfusion culture. This allows selection of clones that have demonstrated high damage resistance, enabling them to withstand the high shear stress and fluid dynamics of perfusion culture without excessive cell damage.
Solution Approach 2:
The patent converts the harmful effect of fluid shear stress into a beneficial selection tool. By deliberately exposing cells to controlled shear stress in micro flow passages during evaluation, the method identifies clones that can withstand such stress, thereby converting a potentially harmful factor into a useful selection criterion for high-productivity perfusion culture.
3Ease of operation
If conventional selection method is used, then ease of operation is maintained, but measurement precision of damage resistance deteriorates
Solution Approach 1:
The patent introduces micro flow passages as an intermediary device to evaluate cell damage resistance. These passages provide a controlled environment that simulates perfusion culture conditions, allowing precise measurement of cell response to shear stress and fluid dynamics without requiring full-scale perfusion culture setup for evaluation.
Solution Approach 2:
The patent replaces complex mechanical evaluation systems with a simplified micro flow passage approach. Instead of requiring large-scale perfusion culture systems to evaluate damage resistance, the method uses small-scale micro flow passages that are easier to operate while providing more precise and controlled damage resistance measurements.
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 the quantification of damage resistance and prediction of cell viability and proliferation rates, facilitating the selection of cells that can withstand the stresses of perfusion culture, thereby enhancing cell survival and productivity.
Implementation Method 1
the damage received by the cell is stress received from a fluid
Implementation Method 2
a first pump for feeding a cell suspension, which is provided upstream of the micro flow passage
Implementation Method 3
a second pump for feeding a cleaning liquid, which is provided upstream of the micro flow passage
Data Source
Figure 1~2
Figure 3
Figure 4~5
AI summary
An object of the present invention is to provide a method for selecting cells, an apparatus for selecting cells, and an apparatus system for selecting cells, which enables evaluation of a damage resistance of the cells in a suspension culture system. According to the present invention, provided is a method for selecting cells including introducing cells into a micro flow passage and allowing the cells to pass through the micro flow passage, evaluating a damage resistance of the cells to damage received by the cells due to passing through the micro flow passage, and selecting the cells based on the evaluation of the damage resistance.