title: Evaluation of a model for seeded isothermal batch protein crystallization.
abstract: Bulk protein crystallization, unlike small molecule crystallization, has found very limited use in biopharmaceutical manufacture. Most work in this area targets obtaining single large crystals for molecular structure determination by crystallography. Design and optimization of bulk crystallization for protein recovery and purification is much less common, and requires a mathematical model for analysis of laboratory data suitable for scale-up purposes. Traditionally, the crystal size distribution and method of moments is used to characterize the crystallization process. A simpler method is presented in this paper that utilizes the desupersaturation curve. The method uses an approach that does not require expensive instrumentation or characterization of the seed crystal size distribution. The method is extended to allow determination of both the mass deposition rate constant and the growth rate order from a single desuperaturation curve. Experimental data for the bulk crystallization of ovalbumin are used to validate the method. The rate constants and rate order obtained using the new method compare well with literature values. Scale-up is illustrated by prediction of the impact of changes in seed mass on protein crystallization. This new method offers a straightforward and low-cost alternative to traditional methods for the analysis and scale-up of protein crystallization data.
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin, 1415 Engineering Drive, Madison, USA.
authors.forename: Martina N
authors.initials: MN
authors.lastname: Carbone
authors.forename: Russell A
authors.initials: RA
authors.lastname: Judge
authors.forename: Mark R
authors.initials: MR
authors.lastname: Etzel
mesh_terms: D003198:Computer Simulation; D003460:Crystallization / Q000379:methods*; D007700:Kinetics; D008956:Models, Chemical; D011506:Proteins / Q000032:analysis* / Q000737:chemistry*; D013696:Temperature
chemical_list: D011506:Proteins