Joseph, A;
Goldrick, S;
Mollet, M;
Turner, R;
Bender, J;
Gruber, D;
Farid, SS;
(2017)
An automated laboratory-scale methodology for the generation of sheared mammalian cell culture samples.
Biotechnology Journal
, 12
(5)
10.1002/biot.201600730.
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Abstract
Continuous disk-stack centrifugation is typically used for the removal of cells and cellular debris from mammalian cell culture broths at manufacturing-scale. The use of scale-down methods to characterise disk-stack centrifugation performance enables substantial reductions in material requirements and allows a much wider design space to be tested than is currently possible at pilot-scale. The process of scaling down centrifugation has historically been challenging due to the difficulties in mimicking the Energy Dissipation Rates (EDRs) in typical machines. This paper describes an alternative and easy-to-assemble automated capillary-based methodology to generate levels of EDRs consistent with those found in a continuous disk-stack centrifuge. Variations in EDR were achieved through changes in capillary internal diameter and the flow rate of operation through the capillary. The EDRs found to match the levels of shear in the feed zone of a pilot-scale centrifuge using the experimental method developed in this paper (2.4×10(5) W/Kg) are consistent with those obtained through previously published computational fluid dynamic (CFD) studies (2.0×10(5) W/Kg). Furthermore, this methodology can be incorporated into existing scale-down methods to model the process performance of continuous disk-stack centrifuges. This was demonstrated through the characterisation of culture hold time, culture temperature and EDRs on centrate quality.
| Type: | Article |
|---|---|
| Title: | An automated laboratory-scale methodology for the generation of sheared mammalian cell culture samples |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/biot.201600730 |
| Publisher version: | http://doi.org/10.1002/biot.201600730 |
| Language: | English |
| Additional information: | © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 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: | Capillary shear, Disk-stack centrifuge, Energy dissipation rate, Mammalian cell, Scale-down |
| 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/1557210 |
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