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.
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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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