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Bulk crystallization is emerging as a new industrial operation for protein recovery. Characterization of bulk protein crystallization is more complex than protein crystallization for structural study where single crystals are grown in flow cells. This is because both nucleation and crystal growth processes are taking place while the supersaturation falls. An algorithm is presented to characterize crystallization using the rates of the two kinetic processes, nucleation and growth. The values of these rates allow ready comparison of the crystallization process under different operating conditions. The crystallization, via adjustment to the isoelectric pH of a fungal lipase from clarified fermentation broth, is described for a batch stirred reactor. A maximum nucleation rate of five to six crystals formed per microliter of suspension per second and a high power dependency (approximate to 11) on the degree of supersaturation were found. The suspended protein crystals were found to grow at a rate of up to 15-20 nm/s and also to exhibit a high power dependency (approximate to 6) of growth rate on the degree of supersaturation. (C) 1998 John Wiley & Sons, Inc.

Bulk crystallization is emerging as a new industrial operation for protein recovery. Characterization of bulk protein crystallization is more complex than protein crystallization for structural study where single crystals are grown in flow cells. This is because both nucleation and crystal growth processes are taking place while the supersaturation falls. An algorithm is presented to characterize crystallization using the rates of the two kinetic processes, nucleation and growth. The values of these rates allow ready comparison of the crystallization process under different operating conditions. The crystallization, via adjustment to the isoelectric pH of a fungal lipase from clarified fermentation broth, is described for a batch stirred reactor. A maximum nucleation rate of five to six crystals formed per microliter of suspension per second and a high power dependency ( approximately 11) on the degree of supersaturation were found. The suspended protein crystals were found to grow at a rate of up to 15-20 nm/s and also to exhibit a high power dependency ( approximately 6) of growth rate on the degree of supersaturation.

Mass crystallization refers to the production of crystalline materials in bulk; it is widely practised in the chemical and process industries. Examples of products produced in this way range from bulk commodity chemicals such as sodium chloride, fertilizer chemicals and sucrose, through products of the fine and speciality chemicals industry typified by dyestuffs intermediates, agrochemicals and catalysts, to pharmaceuticals and ceramic precursors. Production can take place in continuous or batch units and the range of equipment used is vast, reflecting the different properties and production rates of these products.

We evaluated the effect of a range of physiological concentrations of magnesium on calcium oxalate crystallization from artificial urine in a continuous mixed suspension mixed product removal crystallizer at 37C. Magnesium was found to decrease both the growth and nucleation rates of calcium oxalate crystals in the simulated renal environment.

Summary— The effect of glycosaminoglycans on urinary stone formation was evaluated using a mixed suspension, mixed product removal (MSMPR) crystallisation system together with scanning electron microscopy (SEM) to examine the resulting crystals. Chondroitin sulphate was found to decrease the nucleation rate and to promote both the growth rate and suspension density. Results obtained with hyaluronic acid, although inconclusive, are similar to those given by chondroitin sulphate. Heparin sodium salt had a powerful inhibitory effect on both the nucleation rate and the suspension density, the effect increasing in proportion to the heparin concentration. SEM examination showed that the octahedral habit of calcium oxalate dihydrate was modified by the addition of heparin sodium salt and confirmed that the average crystal size in the presence of chondroitin sulphate and hyaluronic acid was significantly greater than the control or that found in the presence of heparin sodium salt.

The in vitro crystallization of calcium oxalate has been investigated by many workers in the field of renal stone disease with a view to providing some insight into the cause as well as the possible treatment of the disorder1–4. Using different techniques and under a variety of conditions, nucleation, growth and aggregation characteristics of this compound have been examined. In particular, the inhibitory effect of several compounds has received a lot of attention5–10. These studies however have all been limited to static, supersaturated systems and have failed to produce definitive nucleation and growth kinetics. Today the role of inhibitors is recognized as being an important factor in the genesis of renal calculi and recent studies have accordingly been directed towards quantitizing this inhibitory power. In attaining accurate quantitative crystallization kinetics, two important approaches have been utilized. The first employs the use of a continuous crystallizer system and the second involves particle size distribution analysis using a Coulter counter. Finlayson11 was the first to describe the usefulness of a continuous crystallizer as a simple urinary tract model while Robertson and Peacock4 determined the size distribution of calcium oxalate crystalluria in normal and stone forming patients. Miller, Randolph and Drach combined these ideas and have determined the crystallization kinetics of calcium oxalate in simulated urine12 and have also measured the inhibition of calcium oxalate crystallization by pyrophosphate and methylene blue13.

We evaluated the effect of a range of physiological concentrations of magnesium on calcium oxalate crystallization from artificial urine in a continuous mixed suspension mixed product removal crystallizer at 37C. Magnesium was found to decrease both the growth and nucleation rates of calcium oxalate crystals in the simulated renal environment.

We determined quantitative nucleation and growth kinetics of calcium oxalate in the presence of various combinations of urine constituents, using a continuous mixed suspension mixed product removal crystallizer and a Coulter counter. Nucleation rates of calcium oxalate from the pure component system were approximately an order of magnitude higher than those from an artificial urine. The presence of citrate inhibited nucleation rates under high conditions. The ions Na+, K+, NH4+, Cl-, and SO42- did not affect the overall kinetics in the synthetic urine. Di- and tri-hydrate products were formed, except when crystallizing from pure components, when only the thermodynamically stable monohydrate was observed.