Fermentation Control via Flow Cytometry Feedback

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Solution Overview

Problem

Current fermentation control methods fail to ensure consistency due to neglect of biological cell status changes, leading to variations in fermentation batches.

Innovation Solution

A method and device that uses a flow cytometer to collect biological cell samples, determine current cell status information, compare it to target information, and adjust nutrient solution flow rates based on the differences to control the fermentation process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If open-loop control with predetermined nutrient solution feeding strategy is used, then the control system is simple, but fermentation consistency cannot be ensured due to ignoring cell status changes

Engineering Contradiction:
Improvecontrol system complexityVSAvoidfermentation consistency
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The patent implements closed-loop feedback control by continuously monitoring cell status parameters (cell concentration, cell size, cell form) via flow cytometry and adjusting nutrient solution feed rate based on the deviation from target status. The control system calculates the difference between current and target cell status and dynamically adjusts the feed rate to minimize this difference, ensuring fermentation consistency while maintaining manageable system complexity through automated feedback mechanisms.

Inventive Principle:
Principle #23Feedback

2Difficulty of detecting and measuring

If traditional monitoring of fermenting environment parameters is used, then the measurement is simple, but cell status changes affecting fermentation process cannot be detected

Engineering Contradiction:
Improvemeasurement difficultyVSAvoidcell status information
Core Design Contradiction:
Difficulty of detecting and measuringVSLoss of information

Solution Approach 1:

The patent introduces flow cytometry as an intermediary measurement tool that bridges the gap between simple environmental monitoring and complex cell status analysis. The flow cytometer measures physical and optical properties of individual cells (light scattering, fluorescence) to derive cell status parameters such as cell concentration, size, and form, providing indirect but effective information about cell physiological state without requiring direct complex biochemical measurements.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If predetermined nutrient solution feeding strategy is applied, then the control process is simple, but variations among different fermentation batches occur

Engineering Contradiction:
Improvecontrol process simplicityVSAvoidfermentation batch consistency
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent transitions from static predetermined feeding strategies to dynamic adaptive control. The nutrient solution feed rate is continuously adjusted based on real-time cell status measurements and the calculated difference from target status. This dynamic adjustment ensures that each fermentation batch adapts to its specific conditions, improving batch-to-batch consistency while maintaining operational simplicity through automated control algorithms.

Inventive Principle:
Principle #15Dynamics

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 real-time, closed-loop feedback control, improving fermentation consistency and quality without requiring complex data analysis, and reduces control delays.

Implementation Method 1

a flow chamber, a laser generator and a detector; said flow chamber is used to allow the biological cells in said samples to align in a single line and form a cell bundle under the restriction of the sheath fluid; said laser generator is used to generate a laser and excite said cell bundle to produce light information

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentEP2267168B1Method and device for controlling fermenting process
Publication Date: 2017.07.26 SIEMENS AG
  • EP2267168B1 patent drawingFigure 1
  • EP2267168B1 patent drawingFigure 2~4
  • EP2267168B1 patent drawingFigure 5

AI summary

The present invention provides method and device for controlling fermenting process, said method comprising: collecting samples of biological cells from fermenting tank, obtaining the state information of the current biological cells according to the samples, comparing the state information of the current biological cells with preset aim state information to obtain the difference between the state information of the current biological cells and preset aim state information, and controlling the feed rate of nutritional solution into fermenting tank. Real time control of biological fermenting process is accomplished according to the state information of the biological cells during fermentation, and the consistency during fermentation is improved. Complicated mathematical model and man-made data analysis are not needed for the method and device. Real time control of biological fermenting process is accomplished according to a feedback loop with simply calculation and control delay is not generated. Automatic control of cells statement in fermentation is achieved.