Combination of a Single Primary Nucleation Event and Secondary Nucleation in Crystallization Processes
The summary below is written by Somnath S. Kadam, on of the authors of the article. The article was published in the journal Crystal Growth & Design in March 2011.
Nucleation is a commonly encountered phenomenon during industrial crystallization but our understanding about it is surprisingly poor. The common perception is that millions of nuclei are formed in a clear solution rapidly if this solution is sufficiently supersaturated. However, we have recently identified a completely different nucleation mechanism: the single nucleus mechanism. This new theory could be formulated on the basis of careful optical observations of the nucleation process at different scales and an analysis of the stochastic nature of the nucleation process.
A cluster of molecules formed by a random process is seen as a precursor of a crystal nucleus. Such a cluster increases or decreases in size by the attachment or the detachment of molecules respectively. After reaching a size that is larger than the critical nucleus size, the cluster can grow without dissolution to form crystals. This random process takes time and is different for each cluster. The stochastic nature of nucleation is reflected in the metastable zone width (MSZW) measurements. MSZW at given operating conditions is the difference between the saturation temperature and the temperature at which crystals are detected.
Around 150 MSZW measurements were performed per concentration at 1 ml scale using Crystal 16 multiple reactor setup (Avantium Technologies) while 4 measurements per concentration were performed at 1l scale. (Kadam, Kramer, ter Horst, 2011).
Figure 1. Relationship between MSZW for paracetamol-water model system at 1 ml and 1 l scale. (Kadam et. al., 2011)
Kadam et. al. deduced a simple scale up rule from the results in Figure 1: The smallest measured MSZW at 1ml coincides with the MSZW at 1l. This kind of a relationship between the MSZWs can be explained by a "Single Nucleus Mechanism". First, a single nucleus is formed on a very active heterogeneous particle. This single nucleus grows out to become a large crystal which eventually undergoes attrition to form secondary nuclei. These secondary nuclei grow out and make a suspension of crystals (Figure 2).
Figure 2. Schematics of the Single Nucleus Mechanism.
The single parent crystal was indeed observed for multiple crystallization systems at 3 ml scale in Crystalline (Avantium Technologies) a multiple reactor set-up with a visualization module. In future research would be focused on exploiting the mechanism to control the number and morphology of the produced crystals in industrial crystallization processes.
References:
1. Kadam, S. S.; Kramer, H. J. M.; ter Horst, J. H., Combination of a Single Primary Nucleation Event and Secondary Nucleation in Crystallization Processes. Crystal Growth & Design 11 (4), 1271-1277.