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Online monitoring of the cell-specific oxygen uptake rate with an in situ combi-sensor

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Abstract

In a biotechnological process, standard monitored process variables are pH, partial oxygen pressure (pO2), and temperature. These process variables are important, but they do not give any information about the metabolic activity of the cell. The ISICOM is an in situ combi-sensor that is measuring the cell-specific oxygen uptake rate (qOUR) online. This variable allows a qualitative judgement of metabolic cell activity. The measuring principle of the ISICOM is based on a volume element enclosed into a small measuring chamber. Inside the measuring chamber, the pO2 and the scattered light is measured. Within a defined measuring interval, the chamber closes, and the oxygen supply for the cells is interrupted. The decreasing oxygen concentration is recorded by the pO2 optode. This measuring principle, known as the dynamic method, determines the oxygen uptake rate (OUR). Together with the scattered light signal, the cell concentration is estimated and the qOUR is available online. The design of the ISICOM is focused on functionality, sterility, long-term stability, and response time behavior so the sensor can be used in bioprocesses. With the ISICOM, measurement of online and in situ measurement of the OUR is possible. The OUR and qOUR online measurement of an animal cell batch cultivation is demonstrated, with maximum values of OUR = 2.5 mmol L−1 h−1 and a qOUR = 9.5 pmol cell−1 day−1. Information about limitation of the primary and secondary substrate is derived by the monitoring of the metabolic cell activity of bacteria and yeast cultivation processes. This sensor contributes to a higher process understanding by offering an online view on to the cell behavior. In the sense of process analytical technology (PAT), this important information is needed for bioprocesses to realize a knowledge base process control.

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Funding

This research was funded by the German Federal Ministry for Economic Affairs and Energy (BMWi) within the Promotion of Joint Industrial Research Program (IGF) due to a decision of the German Bundestag. It was part of the research project 19361 N by the Association for Research in Precision Mechanics, Optics, and Medical Technology (F.O.M.) under the auspices of the German Federation of Industrial Research Associations (AiF).

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Authors and Affiliations

  1. Institut für Technische Chemie, Gottfried Wilhelm Leibniz Universität Hannover, Callinstraße 5, 30167, Hannover, Germany

    Katharina Dahlmann, Christoph Busse, Florian Aupert, Ingo de Vries, Daniel Marquard, Dörte Solle & Thomas Scheper

  2. Sanofi, Industriepark Höchst, 65926, Frankfurt am Main, Germany

    Frank Lammers

Authors
  1. Katharina Dahlmann
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  2. Christoph Busse
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  3. Florian Aupert
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  4. Ingo de Vries
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  5. Daniel Marquard
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  6. Dörte Solle
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  7. Frank Lammers
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  8. Thomas Scheper
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Correspondence to Dörte Solle.

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The authors declare that there are no conflicts of interest.

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Published in the topical collection Advances in Process Analytics and Control Technology with guest editor Christoph Herwig.

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https://doi.org/10.25835/0052186

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Dahlmann, K., Busse, C., Aupert, F. et al. Online monitoring of the cell-specific oxygen uptake rate with an in situ combi-sensor. Anal Bioanal Chem 412, 2111–2121 (2020). https://doi.org/10.1007/s00216-019-02260-9

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  • DOI: https://doi.org/10.1007/s00216-019-02260-9

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