Magnetic Levitation Pump Cell Separation Antibody Quality

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Solution Overview

Problem

In perfusion culture, high cell concentration leads to decreased cell viability and product quality, as excessively grown cells with larger diameters produce antibodies of lower quality and reduced productivity.

Innovation Solution

Adjusting cell concentration in the culture vessel to 3×10^7 to 3×10^8 cells/ml, selectively reducing cells with diameters 1.4 times the average or larger, and maintaining a standard deviation of the cell diameter at A/4 or less, using a magnetic levitation type pump to apply external forces for separation and purification, ensuring a high survival rate and product quality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cell concentration in the culture vessel is increased to enhance productivity, then productivity increases, but cell viability decreases and product quality deteriorates

Engineering Contradiction:
Improveproductivity of antibodiesVSAvoidcell viability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by controlling the cell concentration within a specific range (3×10^7 to 3×10^8 cells/ml) and managing the distribution of cell diameters. By adjusting these parameters, the system maintains high productivity while preventing excessive cell growth that would otherwise reduce viability and product quality.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements partial action by selectively removing only the excessively grown cells (those with diameter 1.4×A or larger) while maintaining the overall high cell concentration needed for productivity. This targeted approach removes the harmful portion without sacrificing the beneficial high-density culture conditions.

Inventive Principle:
Principle #16Partial or excessive action

2Productivity

If cell concentration is increased to enhance productivity, then productivity increases, but product quality decreases due to excessively grown cells

Engineering Contradiction:
Improveproductivity of antibodiesVSAvoidproduct quality
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent controls the distribution of cell diameters by maintaining a specific proportion of cells within the optimal size range (A±A/7) at 50% or more, while limiting excessively large cells (1.4×A or larger) to 5% or less. This parameter control ensures that high productivity is achieved without compromising product quality from oversized cells.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies local quality by differentiating between cell populations based on size and applying different management strategies. Normal-sized cells are maintained for productivity, while excessively grown cells are selectively removed to protect product quality, creating different quality zones within the cell population.

Inventive Principle:
Principle #3Local quality

3Productivity

If cell concentration is increased to enhance productivity, then productivity increases, but the proportion of excessively grown cells increases causing cell division inhibition

Engineering Contradiction:
Improveproductivity of antibodiesVSAvoidcell size distribution
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent maintains stability in cell size distribution by controlling the proportion of cells within the optimal range (A±A/7) to be 50% or more and limiting excessively large cells (1.4×A or larger) to 5% or less. This stable distribution prevents cell division inhibition while maintaining high productivity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback control by continuously monitoring cell concentration and diameter distribution, then adjusting the culture conditions and selective removal processes to maintain the target parameters. This feedback mechanism ensures stable cell size distribution throughout the culture process.

Inventive Principle:
Principle #23Feedback

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

Maintains high productivity while enhancing antibody product quality by controlling cell concentration and removing excessively grown cells, thereby preventing cell division inhibition and viability decrease.

Implementation Method 1

a magnetic levitation type pump that rotates a rotating blade suspended in a cell suspension by means of a magnetic force

Methodology Applied
Scientific EffectMagnetic force: Magnetism

Implementation Method 2

cells having a single cell diameter of 1.4×A or larger may be selectively reduced by applying an external force caused by the liquid flow generated by the pump

Methodology Applied
Scientific EffectLiquid flow generation: Fluid Spray

Data Source

PatentUS11685888B2Method for producing product
Publication Date: 2023.06.27 FUJIFILM CORP
  • US11685888B2 patent drawing
  • US11685888B2 patent drawing
  • US11685888B2 patent drawing

AI summary

A method for producing a product related to the specified technology includes adjusting the concentration of cells in a culture vessel to a value of from 3×107 cells/ml to 3×108 cells/ml; in a case in which the average diameter of single cells in the culture vessel is designated as A, adjusting the number proportion of cells having a single cell diameter of 1.4×A or greater in the culture vessel to 5% or less, and adjusting the number proportion of cells having a single cell diameter in the range of A±A/7 to 50% or more.