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Cell culture state on-line estimation and optimized feeding adjustment and control method

A technology of cell culture and cell state, which is applied in design optimization/simulation, multi-objective optimization, material analysis, etc. It can solve problems such as feedback and adjustment of feed strategy, influence on the synthesis of cell metabolites, and difficulty in accurately describing cells with mathematical models. To achieve the effect of optimizing the cultivation environment and maximizing economic benefits

Inactive Publication Date: 2022-02-11
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, actual cell growth involves complex physical, chemical and biological reactions, and its metabolic flow and kinetic evolution are complex. It is difficult for mathematical models to accurately describe the actual growth process of cells. Therefore, the optimal process curve obtained based on mathematical models may not be able to achieve optimal results. Even seriously affect cell metabolism and product synthesis
In fact, the optimization control method of cell culture and product production process based on mathematical model is essentially an open-loop control, which fails to feed back the optimization effect and adjust the future feeding strategy

Method used

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  • Cell culture state on-line estimation and optimized feeding adjustment and control method
  • Cell culture state on-line estimation and optimized feeding adjustment and control method
  • Cell culture state on-line estimation and optimized feeding adjustment and control method

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Embodiment

[0131] The process of conducting online estimation and optimization regulatory method proposed in the biological production proposed by the present invention is applied to the process of producing polyhydroxybutyric acid (PHB) using fructose and urea flow, and its continuous kinetic state model is:

[0132]

[0133]

[0134]

[0135]

[0136]

[0137]

[0138] Where X 1 For intracellular non-PHB substance concentration, X 2 Product pHB concentration, x 3 Fruit sugar concentration, x 4 Urea concentration, x 5 For the volume of fermentation liquid, the μ bacteria is higher than the growth rate. U 1 Flow rate of fructose, u 2 The flow rate of urea. Define cell culture status x = [x 1 , X 2 , X 3 , X 4 , X 5 ] T , Flow acceleration rate u = [u 1 U 2 ] T . The production process duration is set to 49h, and the Eucalyptus method is used to discretize the above process status model to sampling interval Δ = 4.9h.

[0139] Consider the actual production process, the state of th...

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Abstract

The invention discloses a cell culture state online estimation and feed supplement optimization adjustment and control method. The method comprises the following steps: establishing a cell culture state model; determining constraint conditions required to be met in the cell culture process; selecting an economic benefit optimization target; performing cell state estimation to obtain a cell state estimation value at the current moment; solving the cell culture state model to obtain a cell state vector at a future moment; a nonlinear programming method is adopted to obtain an optimal material supplementing rate track meeting constraint conditions; and implementing the material supplementing rate at the current moment in the material supplementing rate track in the cell culture production process, and repeatedly optimizing and solving the material supplementing rate track until the production process is finished. According to the invention, cell growth state estimation, production benefit optimization, process online control and result real-time feedback are integrated, the growth condition of bacterial cells can be sensed in time, rolling optimization feeding is carried out for different stages, an optimal culture environment is provided, and economic benefit maximization is realized.

Description

Technical field [0001] The present invention relates to the field of biological manufacturing control, and more particularly to a cell culture state online estimation and optimized feed regulation method. Background technique [0002] During biological production, the formation of the product is closely related to the growth and metabolism of the bacterial cell, and the supply of nutrient substrates directly affects cell growth and metabolism, and the substrate flow rate can avoid substrate inhibition, cell hunger and metabolism. Repression, according to different conditions of cell growth and product synthesis, the feed rate of the substrate is optimized, providing the optimal growth environment for microorganisms, is an effective regulatory means for improving the benefits of biological manufacturing process. [0003] The cell culture process is initially rely on manual experience. Gradually study the mathematical model and production goal of cell culture, and then solves the o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G06F30/25G06F30/27G06N3/12G16B5/00G01N21/65G01N21/359G01N21/25G06F111/04G06F111/06
CPCG06F30/25G06F30/27G16B5/00G06N3/126G01N21/25G01N21/359G01N21/65G06F2111/04G06F2111/06
Inventor 刘飞吴杰栾小丽赵顺毅陈珺
Owner JIANGNAN UNIV
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