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Detecting cell lysis using viscosity monitoring in E. coli fermentation to prevent product loss

Newton, JM; Schofield, D; Vlahopoulou, J; Zhou, Y; (2016) Detecting cell lysis using viscosity monitoring in E. coli fermentation to prevent product loss. Biotechnology Progress , 32 (4) pp. 1069-1076. 10.1002/btpr.2292. Green open access

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Abstract

Monitoring the physical or chemical properties of cell broths to infer cell status is often challenging due to the complex nature of the broth. Key factors indicative of cell status include cell density, cell viability, product leakage and DNA release to the fermentation broth. The rapid and accurate prediction of cell status for hosts with intracellular protein products can minimise product loss due to leakage at the onset of cell lysis in fermentation. This paper reports the rheological examination of an industrially relevant E. coli fermentation system producing antibody fragments (Fab'). Viscosity monitoring showed an increase in viscosity during the exponential phase in relation to the cell density increase; this is a relatively flat profile in the stationary phase, followed by a rapid increase which correlated well with product loss, DNA release and loss of cell viability. This phenomenon was observed over several fermentations that a 25% increase in broth viscosity (using induction-point viscosity as a reference) indicated 10% product loss. Our results suggest that viscosity can accurately detect cell lysis and product leakage in post-induction cell cultures, and can identify cell lysis earlier than several other common fermentation monitoring techniques. This work demonstrates the utility of rapidly monitoring the physical properties of fermentation broths, and that viscosity monitoring has the potential to be a tool for process development to determine the optimal harvest time and minimise product loss

Type: Article
Title: Detecting cell lysis using viscosity monitoring in E. coli fermentation to prevent product loss
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/btpr.2292
Publisher version: http://dx.doi.org/10.1002/btpr.2292
Language: English
Additional information: Copyright © 2016 The Authors. Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers, 2016. This is an open access article under the terms of the Creative Com-mons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduc-tion in any medium, provided the original work is properly cited
Keywords: E. coli, Fermentation process monitoring, cell lysis, product leakage, viscosity
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/1489746
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