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Modulator Dynamics Shape the Design Space for Stepwise-Elution Simulated Moving Bed Chromatographic Separations

Wayne, CJ; Velayudhan, A; (2018) Modulator Dynamics Shape the Design Space for Stepwise-Elution Simulated Moving Bed Chromatographic Separations. Biotechnology Journal , 13 (8) , Article 1700664. 10.1002/biot.201700664. Green open access

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Abstract

For proteins and other biological macromolecules, SMB chromatography is best operated non-isocratically. However, traditional modes of non-isocratic SMB operation generate significant mobile-phase modulator dynamics. The mechanisms by which these modulator dynamics affect a separation's success, and thus frame the design space, have yet to be explained quantitatively. Here, the dynamics of the modulator (e.g., salts in ion exchange and hydrophobic interaction chromatography) are explicitly accounted for. This leads to the elucidation of two new design constraints, presented as dimensionless numbers, which quantify the effects of the modulator phenomena and thus predict the success of a non-isocratic SMB separation. Consequently, these two new design constraints re-define the SMB design space. Computational and experimental studies at the boundaries of this design space corroborate the theoretical predictions. The design of efficient and robust operating conditions through use of the new design space is also demonstrated.

Type: Article
Title: Modulator Dynamics Shape the Design Space for Stepwise-Elution Simulated Moving Bed Chromatographic Separations
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/biot.201700664
Publisher version: https://doi.org/10.1002/biot.201700664
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Design space, gradient SMB, modulator perturbation, robust design, simulated moving bed, stepwise-elution SMB, triangle theory
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/10050359
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