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New developments in online OUR monitoring and its application to animal cell cultures

The increasing demand for biopharmaceuticals produced in mammalian cells has driven the industry to enhance the productivity of bioprocesses through intensification of culture process. Fed-batch and perfusion culturing strategies are considered the most attractive choices, but the application of the...

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Published in:Applied microbiology and biotechnology 2019-09, Vol.103 (17), p.6903-6917
Main Authors: Martínez-Monge, I., Roman, R., Comas, P., Fontova, A., Lecina, M., Casablancas, A., Cairó, J. J.
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container_title Applied microbiology and biotechnology
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description The increasing demand for biopharmaceuticals produced in mammalian cells has driven the industry to enhance the productivity of bioprocesses through intensification of culture process. Fed-batch and perfusion culturing strategies are considered the most attractive choices, but the application of these processes requires the availability of reliable online measuring systems for the estimation of cell density and metabolic activity. This manuscript reviews the methods (and the devices used) for monitoring of the oxygen consumption, also known as oxygen uptake rate (OUR), since it is a straightforward parameter to estimate viable cell density and the physiological state of cells. Furthermore, as oxygen plays an important role in the cell metabolism, OUR has also been very useful to estimate nutrient consumption, especially the carbon (glucose and glutamine) and nitrogen (glutamine) sources. Three different methods for the measurement of OUR have been developed up to date, being the dynamic method the golden standard, even though DO and pH perturbations generated in the culture during each measurement. For this, many efforts have been focused in developing non-invasive methods, such as global mass balance or stationary liquid mass balance. The low oxygen consumption rates by the cells and the high accuracy required for oxygen concentration measurement in the gas streams (inlet and outlet) have limited the applicability of the global mass balance methodology in mammalian cell cultures. In contrast, stationary liquid mass balance has successfully been implemented showing very similar OUR profiles compared with those obtained with the dynamic method. The huge amount of studies published in the last years evidence that OUR have become a reliable alternative for the monitoring and control of high cell density culturing strategies with very high productivities.
doi_str_mv 10.1007/s00253-019-09989-4
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subjects Animals
Batch Cell Culture Techniques - instrumentation
Batch Cell Culture Techniques - methods
Batch culture
Biological products
Biomedical and Life Sciences
Bioreactors
Biotechnology
Cell Count
Cell culture
Cell density
Cells
Culture Media - chemistry
Density
Gas streams
Glutamine
Innovations
Internet
Life Sciences
Mammalian cells
Mammals
Mass balance
Measurement methods
Metabolism
Microbial Genetics and Genomics
Microbiology
Mini-Review
Monitoring
Nutrient sources
Nutrients - analysis
Nutrients - metabolism
On-line systems
Online Systems
Oxygen
Oxygen - analysis
Oxygen - metabolism
Oxygen Consumption
Oxygen uptake
Parameter estimation
Perfusion
title New developments in online OUR monitoring and its application to animal cell cultures
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