Characterizing Mesoscopic Species Present in Solution and Modeling Their Roles in Crystallization Processes
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Date
2022
Publication Type
Doctoral Thesis
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Abstract
Crystallization usually occurs in two steps: nucleation (appearance of a crystalline phase) and growth (increase in the size of crystals). In both steps, solute molecules arrange into a highly ordered crystal lattice, thus enabling the separation and purification of solute molecules from the rest. Solute molecules in solution compose a mixture of monomers and molecular clusters. These clusters are typically mesoscopic (i.e., 10 nm to 1000 nm) species (mesospecies), and amorphous mesospecies often play a critical role in multistage crystallization pathways acting as nucleation precursors, heterogeneous nucleation sites, or even nucleation inhibitors. Despite the continuous advancement in knowledge of multistage crystallization pathways, the associated kinetics have been much less understood, because of a lack of suitable methodologies for modeling crystallization while accounting for the role of molecular clusters as well as due to the absence of a suitable technique to obtain the time-resolved concentration of amorphous and crystalline mesospecies.
The purpose of this thesis is twofold. The first is to conceive and validate methods to account for the role of molecular clusters in modeling crystallization phenomena, focusing on the nucleation process. The second is to develop a technique for monitoring the concentration of amorphous and crystalline mesospecies in solution.
The key accomplishments of this thesis are as follows:
- A methodology that considers the effect of molecular cluster formation on the thermodynamic driving force for crystallization and, consequently, on crystallization kinetics has been developed and validated using both in silico and experimental data.
- A kinetic rate equation model for describing the kinetics of growth, primary nucleation, and secondary nucleation caused by interparticle energies (SNIPE) has been developed. Here, SNIPE is a novel surface-induced secondary nucleation mechanism, which has been originally conceived and mathematically modeled in this thesis.
- A nucleation rate model for describing the kinetics of SNIPE has been derived theoretically, verified numerically, and validated experimentally. Furthermore, the model's capability to describe time-resolved experimental data has been proven, while its goodness of fit and theoretical consistency has been assessed in comparison with those of two other, well-known secondary nucleation rate models.
- A depolarized light sheet microscopy device to monitor the concentration of amorphous and crystalline mesospecies present in solution has been conceived and materialized. Using the device, the direct measurement of the crystal nucleation rate in a lab-scale stirred crystallizer has been achieved.
In summary, the results presented in this thesis represent an essential step toward a better understanding and characterization of crystallization processes, particularly nucleation phenomena, where mesospecies play a crucial role.
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Examiner : Mazzotti, Marco
Examiner : Kind, Matthias
Examiner : Briesen, Heiko
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ETH Zurich
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Subject
CRYSTALLIZATION AND CRYSTALLIZERS (PROCESS ENGINEERING); Crystallization kinetics; Modeling and simulation; Online monitoring
Organisational unit
03484 - Mazzotti, Marco (emeritus) / Mazzotti, Marco (emeritus)
Notes
Funding
788607 - Studying Secondary Nucleation for the Intensification of Continuous Crystallization (EC)