The use of crystallization in separation and purification processes is an important and valued methodology in numerous industries, including those manufacturing commodity and specialty chemicals, pharmaceuticals, foodstuffs, and a variety of biologically synthesized products. Crystallizers may be operated in either a batch or continuous mode, and the crystalline product usually must have characteristics that are intrinsic to a specific application and/or that facilitate fluid-solid separation.

Crystallization Science and Technology
The primary purpose of this work is elucidation of the roles of fundamental thermodynamic and kinetic phenomena and of operating protocols in determining crystal quality, especially size distribution, purity, and morphology.

Solid-fluid Equilibrium
When a fluid is in equilibrium with a crystalline solid, the compositions of the coexisting phases depend upon the system characteristics and variables such as temperature, pH, and sometimes pressure. Changing solvents or solvent composition and the presence of other solutes as either major species or minor impurities can have a significant effect on the solubility of the primary solute. Moreover, because crystals can take on various forms, such as solid solutions, hydrates, solvates and polymorphs, the relationships between crystal composition and structure can be quite complex.

Nucleation and Growth Kinetics
The kinetics of crystallization have constituent phenomena in crystal nucleation and growth. The rates at which these occur are dependent on driving forces (usually expressed as supersaturation), physical properties, and a variety of process variables, but relationships between these quantities and crystallization kinetics often are difficult to express quantitatively. Furthermore, these phenomena have great impact on product characteristics, including crystal size distribution, morphology, and purity.

Operating Protocols
Crystal characteristics are strongly dependent on process path. This means that the methods by which crystallizations are conducted can be manipulated to enhance product quality. Such strategies include utilization of modern sensors and control techniques to address product characteristics and process stability. One of the most promising instruments currently available is the focused-beam reflectance monitor (FBRM) which has been used to detect semi-quantitative characteristics of crystal size distributions. Further analysis and modeling is necessary to determine if this instrument can be used for on-line determination of crystal characteristics and, possibly, for control of size distribution.

Although our research is geared to address fundamental issues, the supporting experimental programs often are designed so that the model species utilized in the studies have importance in their own right.

Separation and Purification of Near-Isomorphic Amino Acids
Crystal quality is determined by size distribution, morphology, and purity. All are controlled by a number of factors, including process protocol, intrinsic crystallization kinetics, and system thermodynamics. However, the influence on crystal purity of the thermodynamics of the coexisting solid and liquid phases has only recently been emphasized. For example, we have found that the thermodynamics can determine the purity of a crystalline product when lattice substitution dominates other means by which impurities are incorporated.

Morphology, Hydrates, and Solvates
Form and shape play critical roles in determining many of the properties of crystalline products. These properties may be ones that affect downstream processing, such as solid-liquid separations, or product specifications, such as bulk density or drug efficacy. In this research we address how system thermodynamics and nucleation and growth kinetics affect the morphological crystalline form and the conditions under which hydrates or solvates are formed. For example, the shape of crystals can be altered by the addition of surfactants to the medium from which a product is crystallized. The chemistry of many pharmaceutical products depends upon solution conditions. Isoleucine and other amino acids crystallize as zwitterions or acid or base salts depending upon the pH of the solution. , Finally, it is well known that water or other solvents may crystallize, usually in specific stoichiometric ratios, with the product of interest to form an adducts (hydrates or solvates). The properties of such adducts can vary markedly from those of the primary species, and they can be formed during the crystallization process or as a given species takes up moisture from the prevailing atmosphere. An example of this behavior is found in the use of methanol as an antisolvent in the crystallization of L-serine. In this system, the methanol concentration in the aqueous solution from which L-serine is being crystallized can affect whether a hydrate is formed or not.

Crystallization of Proteins
Protein crystallization is an important step in the recovery, purification, and characterization of these complex biological macromolecules. It is especially significant that crystallization is carried out under conditions that allow recovery and purification without denaturation and loss of biological activity. A number of researchers have noted the difficulty of crystallizing certain proteins; these problems often stem from either lengthy induction periods for nucleation or the imposition of high driving forces for growth that lead to poor crystal quality. Our research has examined the possibility of using specific substrates to catalyze nucleation of selected proteins. The work has addressed inducing protein crystallization from solutions at lower concentrations than those required for spontaneous crystal formation. Not only does this reduce the time for the process, it means that the crystals formed have an opportunity to grow under conditions leading to better crystal quality.

Crystallization of Inorganic Species on Heat-Transfer Surfaces
Fouling of heat-transfer surfaces is an important concern in all processes, but especially when solvent evaporation occurs from a solution containing solutes that can form crystals. In some situations, the problem is exacerbated by the solute having a solubility that decreases with increasing temperature. An example of such is a system is found in the crystallization of burkeite, a double salt of sodium sulfate and sodium carbonate, which occurs in evaporators used to concentrate the liquor obtained from alkali treatment of wood pulp. Either nucleation of burkeite directly on the heat-transfer surface or attachment of fine crystals to that surface is believed to be the mechanism by which fouling occurs. Accordingly, controlling the formation of fine crystals could be important in solving the scaling problem. Nucleation kinetics were determined for model solutions of sodium carbonate and sodium sulfate using a polythermal method to determine metastable zone widths, which were then combined with classical nucleation theory to correlate the effects of temperature and solute concentration on primary nucleation kinetics. Further research determined that the substitution of calcium or other polyvalent ions into the burkeite lattice inhibit nucleation. These results have been combined with pilot-scale experiments on simulated and actual black liquor to elucidate fouling characteristics in a falling-film evaporator.