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 promoting 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 homogeneous 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.
