High-Density Cell Culture Foam Control to Prevent Filter Clogging
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Solution Overview
Problem
Foam formation in cell culture tanks leads to increased poloxamer concentration, causing aggregates that clog filtration membranes and disrupt continuous production, particularly in high-density cell cultures.
Innovation Solution
Adjust the poloxamer concentration or viscosity of the foam liquid to specific conditions, such as 6 times or less the culture solution concentration or 1.5 mPa·s or less at 35°C to 38°C, and control gas aeration and foam removal to prevent aggregate formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If gas aeration is performed during cell culture, then oxygen supply and cell growth are improved, but foam is formed and poloxamer concentration increases causing aggregate formation
Solution Approach 1:
The patent applies parameter changes by controlling the poloxamer concentration in the foam liquid to be 6 times or less than in the culture solution, or controlling the viscosity to be 1.5 mPa·s or less at 35-38°C. This quantitative parameter control prevents aggregate formation while maintaining the beneficial effects of gas aeration for cell growth.
Solution Approach 2:
The patent implements feedback control by monitoring poloxamer concentration or viscosity parameters in the foam liquid and adjusting gas aeration conditions accordingly. When the poloxamer concentration exceeds the threshold (6 times culture solution concentration) or viscosity exceeds 1.5 mPa·s, the gas aeration is adjusted to prevent aggregate formation, creating a closed-loop control system.
2Stability of the object's composition
If poloxamer concentration in foam increases, then foam stability is improved, but aggregates are generated and filtration membrane clogging is promoted
Solution Approach 1:
The patent maintains foam stability while preventing aggregate formation by controlling key parameters: poloxamer concentration ratio (foam to culture solution) at 6 times or less, and viscosity at 1.5 mPa·s or less at 35-38°C. These parameter thresholds ensure foam remains stable for gas aeration purposes without causing filtration membrane clogging.
3Productivity
If high-density cell culture is performed, then production efficiency is improved, but aggregates in foam fall into culture solution and membrane clogging is promoted
Solution Approach 1:
The patent enables extended continuous production in high-density cell culture by controlling foam liquid parameters (poloxamer concentration ratio ≤6 times, viscosity ≤1.5 mPa·s at 35-38°C). This prevents aggregate formation that would otherwise fall into the culture solution and clog filtration membranes, allowing continuous operation for 60 days or more.
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
Suppresses foam aggregates, maintaining culture stability and extending continuous production periods by preventing membrane clogging.
Implementation Method 1
a poloxamer concentration of a foam liquid or a viscosity of the foam liquid satisfies a predetermined condition
Implementation Method 2
adjusting the poloxamer concentration of a foam liquid constituting the foam to be 6 times or less the poloxamer concentration in the culture solution, or adjusting the viscosity of the foam liquid constituting the foam to be 1.5 mPa·s or less under conditions of 35°C or higher and 38°C or lower
Implementation Method 3
step A or step B includes a step of aerating the culture solution with a gas
Implementation Method 4
foam is formed in an upper portion of the culture tank by gas aeration during culture
Data Source
Figure 1
AI summary
An object of the present invention is to provide a cell culture method and a production method for a product, in which an occurrence of aggregates in foam is suppressed. According to the present invention, there is provided a cell culture method of culturing cells at a cell density of 30 × 106 cells/mL or more and 400 × 106 cells/mL or less in a culture solution, the method including: step A of adjusting a poloxamer concentration in a foam liquid constituting foam to be 6 times or less a poloxamer concentration in the culture solution; or step B of adjusting a viscosity of the foam liquid constituting the foam to be 1.5 mPa·s or less under conditions of 35°C or higher and 38°C or lower.