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Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes
The real-time measurement of biomass has been addressed since many years. The quantification of biomass in the induction phase of a recombinant bioprocess is not straight forward, since biological burden, caused by protein expression, can have a significant impact on the cell morphology and physiolo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755222/ https://www.ncbi.nlm.nih.gov/pubmed/23178981 http://dx.doi.org/10.1007/s00449-012-0848-4 |
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author | Wechselberger, Patrick Sagmeister, Patrick Herwig, Christoph |
author_facet | Wechselberger, Patrick Sagmeister, Patrick Herwig, Christoph |
author_sort | Wechselberger, Patrick |
collection | PubMed |
description | The real-time measurement of biomass has been addressed since many years. The quantification of biomass in the induction phase of a recombinant bioprocess is not straight forward, since biological burden, caused by protein expression, can have a significant impact on the cell morphology and physiology. This variability potentially leads to poor generalization of the biomass estimation, hence is a very important issue in the dynamic field of process development with frequently changing processes and producer lines. We want to present a method to quantify “biomass” in real-time which avoids off-line sampling and the need for representative training data sets. This generally applicable soft-sensor, based on first principles, was used for the quantification of biomass in induced recombinant fed-batch processes. Results were compared with “state of the art” methods to estimate the biomass concentration and the specific growth rate µ. Gross errors such as wrong stoichiometric assumptions or sensor failure were detected automatically. This method allows for variable model coefficients such as yields in contrast to other process models, hence does not require prior experiments. It can be easily adapted to a different growth stoichiometry; hence the method provides good generalization, also for induced culture mode. This approach estimates the biomass (or anabolic bioconversion) in induced fed-batch cultures in real-time and provides this key variable for process development for control purposes. |
format | Online Article Text |
id | pubmed-3755222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-37552222013-09-05 Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes Wechselberger, Patrick Sagmeister, Patrick Herwig, Christoph Bioprocess Biosyst Eng Original Paper The real-time measurement of biomass has been addressed since many years. The quantification of biomass in the induction phase of a recombinant bioprocess is not straight forward, since biological burden, caused by protein expression, can have a significant impact on the cell morphology and physiology. This variability potentially leads to poor generalization of the biomass estimation, hence is a very important issue in the dynamic field of process development with frequently changing processes and producer lines. We want to present a method to quantify “biomass” in real-time which avoids off-line sampling and the need for representative training data sets. This generally applicable soft-sensor, based on first principles, was used for the quantification of biomass in induced recombinant fed-batch processes. Results were compared with “state of the art” methods to estimate the biomass concentration and the specific growth rate µ. Gross errors such as wrong stoichiometric assumptions or sensor failure were detected automatically. This method allows for variable model coefficients such as yields in contrast to other process models, hence does not require prior experiments. It can be easily adapted to a different growth stoichiometry; hence the method provides good generalization, also for induced culture mode. This approach estimates the biomass (or anabolic bioconversion) in induced fed-batch cultures in real-time and provides this key variable for process development for control purposes. Springer Berlin Heidelberg 2012-11-23 2013 /pmc/articles/PMC3755222/ /pubmed/23178981 http://dx.doi.org/10.1007/s00449-012-0848-4 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Paper Wechselberger, Patrick Sagmeister, Patrick Herwig, Christoph Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes |
title | Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes |
title_full | Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes |
title_fullStr | Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes |
title_full_unstemmed | Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes |
title_short | Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes |
title_sort | real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755222/ https://www.ncbi.nlm.nih.gov/pubmed/23178981 http://dx.doi.org/10.1007/s00449-012-0848-4 |
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