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

I. Martínez-Monge, R. Roman, P. Comas, A. Fontova, M. Lecina, A. Casablancas, J. J. Cairó

Research output: Contribution to journalReview articleResearchpeer-review

2 Citations (Scopus)

Abstract

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. 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.
Original languageEnglish
Pages (from-to)6903-6917
Number of pages15
JournalApplied Microbiology and Biotechnology
Volume103
Issue number17
DOIs
Publication statusPublished - 5 Sep 2019

Keywords

  • Bioprocess control
  • Mammalian cell culture
  • OUR
  • Oxygen uptake rate
  • Cell Count
  • Oxygen Consumption
  • Online Systems
  • Animals
  • Batch Cell Culture Techniques/instrumentation
  • Bioreactors
  • Oxygen/analysis
  • Culture Media/chemistry
  • Nutrients/analysis
  • HIGH-DENSITY
  • CHO-CELLS
  • MAMMALIAN-CELLS
  • GAS-ANALYSIS
  • OXYGEN-UPTAKE RATE
  • FED-BATCH CULTURE
  • GLUCOSE
  • METABOLIC FLUX ANALYSIS
  • DISSOLVED-OXYGEN
  • HYBRIDOMA GROWTH

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