ISPR with Crystallization

A further interesting method of ISPR that has received quite some attention for reductions is the use of ISPR with crystallization (in situ product crystallization 

ISPC looks attractive with reasonable productivity improvements reported [43], but clearly for the future a wider range of processes as well as issues like effective particle-particle separation need to be examined. As with all cases, a comparison with other methods is also required to assist implementation. 

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When reactions are reversible or products unstable, it is attractive to int ate recovery and (bio-)reaction, that is in situ product removal (ISPR). Compatibility of bioconversion and separation conditions is a key issue in ISPR. It will be demonstrated in a later section that constraints in an integrated system are completely different from those in the individual, non-int ated process steps. It may also be attractive to combine separation steps. A well-known example is crystallization with a withdrawal of coarse crystals (integration of molecular and mechanical separations). Often, an optimal integrated system will operate imder conditions that are not equal to those of the individual and non-integrated conversion and separation steps. This is process integration at the level of unit operations. 

Direct product precipitation allows pure recovery without need of further separation steps. Contamination by organic solvents is thereby avoided, which is often a problem for drug and food applications. A fermentation process that removes lactic acid by in situ crystallization with calcium ions was one of the first successful applications of a whole cell ISPR process [11]. Recently, the potential of in situ precipitation was shown for the solid-solid enzymatic conversion of Ca-maleate to Ca-D-malate. In situ crystallization processes employing whole cells are expected to be increasingly applied in the recovery of carboxylic acids, antibiotics, and proteins. 

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