Inline Medium Dilution Bioreactor for Logistics Optimization

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Solution Overview

Problem

Large-scale bioreactor systems face logistical and economic challenges in optimizing medium use and handling, particularly in continuous fermentation processes, due to the need for large volumes of fresh medium and complex media logistics.

Innovation Solution

A bioreactor system employing continuous inline medium dilution, where concentrated medium and nutrients are blended with water or buffer just before use, reducing container size requirements and allowing for efficient mixing of different media components at varying concentrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If large volumes of fresh medium are supplied daily to large-scale bioreactors, then cell culture productivity is maintained, but logistical complexity and handling costs increase significantly

Engineering Contradiction:
Improvecell culture productivityVSAvoidmedia logistics complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The medium is segmented into concentrate and diluent components. The concentrate contains all essential nutrients at high concentrations, while the diluent (water or buffer) is added in controlled amounts during perfusion. This segmentation allows the system to maintain productivity with reduced logistical complexity, as only the concentrated medium needs to be stored and handled in significant quantities.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from storing and handling large volumes of diluted medium to storing and handling small volumes of concentrated medium. By changing the concentration dimension, the system achieves the same nutritional delivery with reduced volume, thereby simplifying media logistics while maintaining cell culture productivity.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Volume of stationary object

If concentrated medium is stored and diluted inline, then container size requirements are reduced, but inline dilution system complexity is introduced

Engineering Contradiction:
Improvecontainer sizeVSAvoidinline dilution system complexity
Core Design Contradiction:
Volume of stationary objectVSDevice complexity

Solution Approach 1:

The medium is pre-concentrated and pre-formulated with all necessary nutrients before storage. This preliminary concentration action eliminates the need for large storage containers and reduces the volume that needs to be handled. The inline dilution system then simply adds the appropriate amount of diluent during perfusion, maintaining simplicity despite the added concentration step.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If multiple media components are blended from independent stock solutions, then media composition flexibility is improved, but blending system complexity increases

Engineering Contradiction:
Improvemedia composition flexibilityVSAvoidblending system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The medium is segmented into essential nutrient components that are combined in a concentrated formulation. This segmentation allows for flexible adjustment of individual nutrient concentrations while maintaining a manageable number of stock solutions. The inline blending system mixes these segmented components in controlled proportions, achieving composition flexibility without excessive complexity.

Inventive Principle:
Principle #1Segmentation

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 significantly reduces container size needs, enhances media efficiency, and lowers costs associated with medium delivery and handling, while maintaining precise control over critical process parameters like pH and osmolality.

Implementation Method 1

concentrated medium and nutrients are blended with water or buffer by inline dilution

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentUS11390839B2Bioreactor system and method for producing a biopolymer
Publication Date: 2022.07.19 KMK BIOLOGIKS AS
  • US11390839B2 patent drawing
  • US11390839B2 patent drawing

AI summary

Provided is a bioreactor system and a fermentation process employing continuous inline medium dilution in which concentrated medium and nutrients are blended with water or buffer and fed to the cell culture vessel of a bioreactor system, e.g. for production of antibodies and other recombinant proteins by mammalian cells.