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Predicting the metabolic condition of a cell culture

A cell culture and cell technology, applied in the field of cells, can solve problems such as inability to adapt and inflexible models

Pending Publication Date: 2020-12-22
F HOFFMANN LA ROCHE & CO AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, models generated in this way are not very flexible and cannot be adapted to the metabolism of other cell types without considerable human effort.

Method used

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  • Predicting the metabolic condition of a cell culture
  • Predicting the metabolic condition of a cell culture
  • Predicting the metabolic condition of a cell culture

Examples

Experimental program
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Embodiment Construction

[0193] specific implementation plan

[0194] figure 1 A flowchart showing a method according to an embodiment for predicting the metabolic state of a cell culture of CHO cells, which method is equally applicable to other cell types.

[0195] Step 102: Model generation

[0196] Processes in bioreactors can be described mathematically. First, one should consider mapping temporal changes in the concentration or amount of a substance of interest in the reaction medium (e.g., progression of substrate amount, product amount, cell density). The formula is based on mass balance and consists of terms describing the reaction of species and a convection term that includes any flow of species into and out of the reactor. Its general application (see Section 4.2 in the Appendix, [51]):

[0197]

[0198] or in equations:

[0199]

[0200] where m is the amount of substance in the reaction medium, t is the process time, or is the volume flow at the inlet or outlet, c zu or...

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Abstract

The invention relates to a method for predicting the metabolic condition of a cell culture of cells of a specific cell type. The method comprises providing (102) a metabolic model (402) of a cell of the specific cell type and carrying out the following steps at each of a plurality of points in time during the cultivation of the cell culture: receiving (106) measured concentrations of several extracellular metabolites and a measured cell density in the culture medium; inputting (108) the received measured values as input parameter values into a trained machine learning program logic-MLP (218);predicting (110) extracellular flows (408) of the extracellular metabolites at a future point in time by means of the MLP; carrying out (112) a metabolic flow analysis for calculating the intracellular flows at the future point in time on the basis of the predicted extracellular flows and the stoichiometric equations of the metabolic model.

Description

technical field [0001] The present invention relates to the prediction of the metabolic state of cells, especially cells maintained in cell culture. Background technique [0002] In recent years, the pharmaceutical industry has made significantly increased efforts to improve the efficiency of development, production, and quality assurance processes by increasing focus on process analysis, monitoring, and control means. This trend also particularly affects the operation of cell culture reactors for the production of pharmaceutically relevant molecules, especially macromolecules, such as proteins. [0003] However, modeling cellular metabolism and fermentation processes in the context of pharmaceutical research and development is a major technical challenge: the metabolism of cells (especially eukaryotic cells) has very complex Linear chemical reaction cascade feature. [0004] For example, it is well known to analyze metabolic flux using metabolic flux analysis (MFA, metabo...

Claims

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Application Information

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IPC IPC(8): G01N33/50
CPCG01N33/5005G16B5/30G16B40/20G06N20/00G16B5/00C12M41/38C12M41/46C12N5/0018G06N3/02
Inventor W·保罗A·莫尔S·霍尔奇
Owner F HOFFMANN LA ROCHE & CO AG
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