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Applied Microbiology and Biotechnology

, Volume 103, Issue 17, pp 6903–6917 | Cite as

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

  • I. Martínez-MongeEmail author
  • R. Roman
  • P. Comas
  • A. Fontova
  • M. Lecina
  • A. Casablancas
  • J. J. Cairó
Mini-Review
  • 148 Downloads

Abstract

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.

Keywords

Oxygen uptake rate OUR Mammalian cell culture Bioprocess control 

Notes

Funding information

This study was financially supported by the grant FI-DGR (Generalitat de Catalunya, Catalonia, Spain), the Novo Nordisk Foundation, and the two NNF grant numbers NNF10CC1016517 and NNF14OC0009473.

Compliance with ethical standards

The authors are aware with the ethical responsibilities required by the journal and are committed to comply them.

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Novo Nordisk Foundation Center for BiosustainabilityTechnical University of DenmarkKgs. LyngbyDenmark
  2. 2.Department of Chemical, Biological and Environmental EngineeringUniversitat Autònoma de BarcelonaCerdanyola del VallèsSpain
  3. 3.Electronic Engineering DepartmentUniversitat Politècnica de CatalunyaBarcelonaSpain

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