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On-line control of glucose concentration in high-yielding mammalian cell cultures enabled through oxygen transfer rate measurements

Goldrick, S; Lee, K; Spencer, C; Holmes, W; Kuiper, M; Turner, R; Farid, SS; (2018) On-line control of glucose concentration in high-yielding mammalian cell cultures enabled through oxygen transfer rate measurements. Biotechnology Journal , 13 (4) , Article 1700607. 10.1002/biot.201700607. Green open access

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Abstract

Glucose control is vital to ensure consistent growth and protein production in mammalian cell cultures. The typical fed-batch glucose control strategy involving bolus glucose additions based on infrequent off-line daily samples results in cells experiencing significant glucose concentration fluctuations that can influence product quality and growth. This study proposes an on-line method to control and manipulate glucose utilising readily available process measurements. The method generates a correlation between the cumulative oxygen transfer rate and the cumulative glucose consumed. This correlation generates an on-line prediction of glucose that has been successfully incorporated into a control algorithm manipulating the glucose feed-rate. This advanced process control (APC) strategy enables the glucose concentration to be maintained at an adjustable set-point and has been found to significantly reduce the deviation in glucose concentration in comparison to conventional operation. This method has been validated to produce various therapeutic proteins across cell lines with different glucose consumption demands and was successfully demonstrated on micro (15 mL), laboratory (7 L) and pilot (50 L) scale systems. This novel APC strategy is simple to implement and offers the potential to significantly enhance the glucose control strategy for scales spanning micro-scale systems through to full scale industrial bioreactors.

Type: Article
Title: On-line control of glucose concentration in high-yielding mammalian cell cultures enabled through oxygen transfer rate measurements
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/biot.201700607
Publisher version: http://dx.doi.org/10.1002/biot.201700607
Language: English
Additional information: © 2018 The Authors. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Advanced process control (APC), glucose control, mammalian cell culture, oxygen transfer rate, process analytic technology (PAT), soft sensor
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10040910
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