Fermentation Release Systems for Defined Nutrient Kinetics

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Solution Overview

Problem

Current fed-batch fermentation methods face challenges in efficiently screening microorganisms for optimal yield due to limited parallel operation capabilities and undefined nutrient release rates, which hinder gas exchange and require extensive equipment and handling efforts.

Innovation Solution

The method involves attaching release systems formed by a diffusion barrier with embedded nutrients to the inner surfaces of reaction vessels, ensuring defined contact and controlled nutrient release, while maintaining unobstructed gas exchange, and integrating these systems into microtiter plates for efficient parallel fermentation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If release systems are suspended in culture liquid, then nutrient release occurs, but the release rate becomes undetermined and gas exchange is hindered

Engineering Contradiction:
Improvenutrient releaseVSAvoidrelease rate definition
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The release system is segmented into two distinct functional layers: a diffusion barrier layer that controls nutrient release rate and a nutrient-containing layer that provides the nutrients. This segmentation allows the diffusion barrier to define a precise, reproducible release rate while the nutrient layer supplies adequate nutrients, resolving the contradiction between nutrient release and defined release rate.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the release system have different properties: the diffusion barrier layer has controlled porosity and thickness to regulate release rate, while the nutrient-containing layer has high nutrient concentration. This local quality differentiation enables simultaneous achievement of defined release kinetics and adequate nutrient supply.

Inventive Principle:
Principle #3Local quality

2Productivity

If more reaction vessels are operated in parallel, then screening efficiency increases, but equipment complexity and handling effort increase

Engineering Contradiction:
Improvescreening efficiencyVSAvoidequipment and handling
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The release systems are designed as universal components that can be attached to various reaction vessel types (shake flasks, Erlenmeyer flasks, bioreactors) and work with different nutrient types. This universality allows parallel operation of many vessels without requiring vessel-specific dosing equipment, maintaining simplicity while enabling high-throughput screening.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The release systems are designed as inexpensive, disposable components that can be easily attached and removed. This allows rapid exchange between experiments and parallel operation of multiple vessels without complex cleaning or sterilization procedures, reducing handling effort while maintaining high productivity.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Manufacturing precision

If conventional dosing technology is used, then nutrient addition can be controlled, but the system requires extensive equipment and is difficult to automate

Engineering Contradiction:
Improvedosing precisionVSAvoiddosing equipment
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The release system performs self-dosing through controlled diffusion of nutrients from the nutrient-containing layer through the diffusion barrier. This eliminates the need for external pumps, valves, and control systems, achieving precise nutrient delivery without complex equipment that would be difficult to automate.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The mechanical dosing system (pumps, valves, dosing lines) is replaced by a passive diffusion-based release system. The controlled diffusion process through the barrier provides precise nutrient release kinetics without requiring mechanical actuation or electronic control, simplifying the system and enabling easy automation.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 allows for cost-effective, automated, and efficient development of dosing strategies with defined nutrient release kinetics, supporting large-scale parallel fermentations and reducing equipment-related costs by enabling precise control over nutrient supply and gas exchange.

Implementation Method 1

release systems which are formed by a diffusion barrier in which nutrients are embedded

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

Energy can be input into the culture liquid during fermentation

Methodology Applied
Scientific EffectStirring: Stirring

Data Source

PatentEP1879995B1Fermentation method and apparatus for its implementation
Publication Date: 2012.04.04 RWTH AACHEN UNIV
  • EP1879995B1 patent drawingFigure 1A~1D
  • EP1879995B1 patent drawingFigure 2~3

AI summary

The invention relates to a fermentation method with controlled supply of nutrients to the culturing fluid in two or more reaction vessels, the nutrients being delivered to each reaction vessel by at least one release system in each case. In order to allow the development and optimization of metering strategies for fed-batch fermentations featuring relatively simple apparatus and defined release rates, it is proposed in accordance with the invention that the release systems be attached to the inner faces of the reaction vessels in a region which comes into contact with the culturing fluid. Moreover, the invention relates to apparatus for implementing a fermentation with controlled supply of nutrients from release systems to the culturing fluid in two or more interconnected reaction vessels.