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On the fluid dynamics of a laboratory scale single-use stirred bioreactor.

Odeleye, AO; Marsh, DT; Osborne, MD; Lye, GJ; Micheletti, M; (2014) On the fluid dynamics of a laboratory scale single-use stirred bioreactor. Chem Eng Sci , 111 (100) 299 - 312. 10.1016/j.ces.2014.02.032. Green open access

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Abstract

The commercial success of mammalian cell-derived recombinant proteins has fostered an increase in demand for novel single-use bioreactor (SUB) systems that facilitate greater productivity, increased flexibility and reduced costs (Zhang et al., 2010). These systems exhibit fluid flow regimes unlike those encountered in traditional glass/stainless steel bioreactors because of the way in which they are designed. With such disparate hydrodynamic environments between SUBs currently on the market, traditional scale-up approaches applied to stirred tanks should be revised. One such SUB is the Mobius(®) 3 L CellReady, which consists of an upward-pumping marine scoping impeller. This work represents the first experimental study of the flow within the CellReady using a Particle Image Velocimetry (PIV) approach, combined with a biological study into the impact of these fluid dynamic characteristics on cell culture performance. The PIV study was conducted within the actual vessel, rather than using a purpose-built mimic. PIV measurements conveyed a degree of fluid compartmentalisation resulting from the up-pumping impeller. Both impeller tip speed and fluid working volume had an impact upon the fluid velocities and spatial distribution of turbulence within the vessel. Cell cultures were conducted using the GS-CHO cell-line (Lonza) producing an IgG4 antibody. Disparity in cellular growth and viability throughout the range of operating conditions used (80-350 rpm and 1-2.4 L working volume) was not substantial, although a significant reduction in recombinant protein productivity was found at 350 rpm and 1 L working volume (corresponding to the highest Reynolds number tested in this work). The study shows promise in the use of PIV to improve understanding of the hydrodynamic environment within individual SUBs and allows identification of the critical hydrodynamic parameters under the different flow regimes for compatibility and scalability across the range of bioreactor platforms.

Type: Article
Title: On the fluid dynamics of a laboratory scale single-use stirred bioreactor.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ces.2014.02.032
Publisher version: http://dx.doi.org/10.1016/j.ces.2014.02.032
Additional information: © 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). PMCID: PMC4015722
Keywords: Bioreactors, Hydrodynamics, Mammalian Cell Culture, PIV, Scale-up, Single-use
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/1431201
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