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Theoretical Analysis and Experimental Investigation of Simulated Moving Bed Chromatography for the Purification of Protein Mixtures

Wayne, Chris J.; (2019) Theoretical Analysis and Experimental Investigation of Simulated Moving Bed Chromatography for the Purification of Protein Mixtures. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Stepwise-Elution Simulated Moving Bed Chromatography (SE-SMB) is a promising method for ‘intensification’ of polishing chromatographic processes in downstream bioprocessing. This is because SE-SMB systems are continuous, capable of high-resolution separations, efficient in their utilization of chromatographic resins, well-suited to non-isocratic proteinaceous separation problems operated under high feed-loading conditions, and highly productive. However, there are a number of theoretical and practical problems which have impeded industrial interest in the adoption of SE-SMB separations into downstream processes. Fundamental phenomena, such as the modulator dynamics of SE-SMB systems, have yet to be theoretically analysed. Consequently, important practical questions – such as how productive and high-resolution separations may be best achieved through SE-SMB systems – remain unanswered. Furthermore, the complexity and operational fragility of SE-SMB systems require much improvement in their ‘robustness’ before any consideration of their application to industrial purification of therapeutic proteins may be entertained. This thesis constitutes an initial investigation of the theoretical and practical issues which arise concerning the application of SE-SMB to industrial bioseparations. Regarding the theoretical issues, an analysis of modulator dynamics in SE-SMB systems is presented. This provides new insights into how such systems – both for binary and ternary separations - should be designed for productive and robust operations. Furthermore, the behaviour of SE-SMB systems under high feedloading conditions is also investigated. Regarding practical issues, experimental SMB separations of a challenging proteinaceous mixture are demonstrated, and simulated comparisons are used to investigate the comparative performance of various intensified processes. Finally, an exploration of SE-SMB fault detection and diagnosis methods is undertaken. The results suggest that SE-SMB chromatography may be ‘de-risked’ to such an extent that, with future development, it becomes an attractive option for incorporation into industrial bioprocesses.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Theoretical Analysis and Experimental Investigation of Simulated Moving Bed Chromatography for the Purification of Protein Mixtures
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms.
UCL classification: UCL > Provost and Vice Provost Offices
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/10072569
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