Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.779333
Title: Theoretical analysis and experimental investigation of simulated moving bed chromatography for the purification of protein mixtures
Author: Wayne, Chris J.
ISNI:       0000 0004 7965 0291
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.779333  DOI: Not available
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