Model-based approach to template-induced macromolecule crystallisation
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Biomacromolecules have intricate crystallisation behaviour due to their size and many interactions in solution and can often only crystallise in narrow ranges of experimental conditions. High solute concentrations are needed for crystal nucleation and growth, exceeding those eluted upstream and therefore preventing the adoption of crystallisation in downstream separation steps. By pro
moting molecular aggregation and nucleation via a lowered energy barrier, heterogeneous surfaces or templates can relax the supersaturation requirements and widen the crystallisation operating space. Though templates are promising candidates for process optimisation, their experimental testing has generally been limited to small-volume experiments, and quantification of their impact on process intensification and quality metrics at higher volumes remains unexplored. To address the knowledge gap, a model-based investigation of template-induced protein crystallisation systems through evaluation of key metrics is presented. Porous silica nano-particles with three chemical functionalisations (hydroxyl, carboxyl and butyl) are added to batch lysozyme crystallisation experiments at 40ml. Crystallisation population balance models are parametrised with an experimentally-validated parameter estimation methodology and further experiments are simulated. The templates appear to lower the estimated interfacial energy compared to the homoge
neous case, leading to nucleation rate profiles which are less dependent on supersaturation. For this reason, the templates can crystallize quicker than the homogeneous system, particularly at lower initial concentrations. The simulation results highlight the ability of heteronucleants to alter nucleation rate profiles, and their potential to be used as process optimisation and intensification
tools for biomacromolecule purification.
moting molecular aggregation and nucleation via a lowered energy barrier, heterogeneous surfaces or templates can relax the supersaturation requirements and widen the crystallisation operating space. Though templates are promising candidates for process optimisation, their experimental testing has generally been limited to small-volume experiments, and quantification of their impact on process intensification and quality metrics at higher volumes remains unexplored. To address the knowledge gap, a model-based investigation of template-induced protein crystallisation systems through evaluation of key metrics is presented. Porous silica nano-particles with three chemical functionalisations (hydroxyl, carboxyl and butyl) are added to batch lysozyme crystallisation experiments at 40ml. Crystallisation population balance models are parametrised with an experimentally-validated parameter estimation methodology and further experiments are simulated. The templates appear to lower the estimated interfacial energy compared to the homoge
neous case, leading to nucleation rate profiles which are less dependent on supersaturation. For this reason, the templates can crystallize quicker than the homogeneous system, particularly at lower initial concentrations. The simulation results highlight the ability of heteronucleants to alter nucleation rate profiles, and their potential to be used as process optimisation and intensification
tools for biomacromolecule purification.
Date Issued
2025-07-01
Date Acceptance
2025-07-01
Citation
WSEAS Transactions on Systems and Control, 2025, 4 (1), pp.2504-2509
ISSN
1991-8763
Publisher
World Scientific and Engineering Academy and Society (WSEAS)
Start Page
2504
End Page
2509
Journal / Book Title
WSEAS Transactions on Systems and Control
Volume
4
Issue
1
Copyright Statement
© 2025 by the authors. Licensed to PSEcommunity.org and PSE Press. This is an open access article under the creative com mons CC-BY licensing terms. Credit must be given to creator and adaptations must be shared under the same terms. See https://creativecommons.org/licenses/by/4.0/
License URL
Identifier
10.69997/sct.131246
Subjects
Protein crystallisation
Template-induced nucleation
Population-balance modelling
Publication Status
Published
Date Publish Online
2025-06-27