324 Fermentation and Biochemical Engineering Handbook UF offers many advantages over traditional processes such as vacuum evaporation or vacuum evaporation with desalting. These include higher product purity and yields(concentration factor 10 to 50), lower operating costs, ability to fractionate when the molecular sizes of the components differ by a factor of at least 10. The availability of a wide range of Mwco membranes enables the selection of a suitable membrane to maximize flux without substantially compromising retention. UF canalso minimize enzyme inactivation or denaturation by maintaining a constant pH and ionic strength Other techniques such as solvent precipitation, crystallization or solvent extraction may sometimes denature the product owing to phase change UF performance, however, may be influenced by process variables such as pH, nature of ions and ionic strength, temperature and shear. For xample, Melling 50] has reported the effect of pH on the specific enzyme activity of E-coli penicillinase in the ph range 5 to 8. Effects of shear inactivation associated with pumping effects are described by o sullivan et al.(23 Recessed impeller centrifugal pumps or positive displacement pumps may be used to minimize enzyme inactivation due to shear 7.3 Microfiltration for Removal of Microorganisms or Cell Debris In recent years there has been a significant interest in the use of micro- organism-based fermentations for the production of many specialty hemicals (511[531 The product of interest may be produced by either an extracellular or intracellular process relative to the microorganisms. In either of these situations, one of the key steps is the efficient removal of microorgani cell debris from the fermentation broth. 154(551 In biotechnology terminology this step, where cells are separated from the soluble components of the broth, is described as cell harvesting Filtration is often preferred over centrifugation due to problems associated with poor separation which results in either reduced product yield or purity. Aerosol generation during centrifugation could be a maje problem. This can be alleviated in the CfF mode due to the closed nature of system operation. Additionally, centrifuges may require high since there is no appreciable density difference between the bacterial cell walls and the surrounding medium. Pre-coat filtration, when applicable, will suffer from reduced product yield and lower filtration rates (e.g, 0.7 to 16L/hrm2.52324 Fermentation and Biochemical Engineering Handbook UF offers many advantages over traditional processes such as vacuum evaporation or vacuum evaporation with desalting. These include higher product purity and yields (concentration factor 10 to 50), lower operating costs, ability to fractionate when the molecular sizes of the components differ by a factor of at least 10. The availability of a wide range of MWCO membranes enables the selection of a suitable membrane to maximize flux without substantially compromising retention. UF can also minimize enzyme inactivation or denaturation by maintaining a constant pH and ionic strength. Other techniques such as solvent precipitation, crystallization or solvent extraction may sometimes denature the product owing to phase change.i8] UF performance, however, may be influenced by process variables such as pH, nature of ions and ionic strength, temperature and shear. For example, Melling[sol has reported the effect of pH on the specific enzyme activity of E-coli penicillinase in the pH range 5 to 8. Effects of shear inactivation associated with pumping effects are described by O’Sullivan et a1.[12] Recessed impeller centrifugal pumps or positive displacement pumps may be used to minimize enzyme inactivation due to shear. 7.3 Microfiltration for Removal of Microorganisms or Cell Debris In recent years there has been a significant interest in the use of micro￾organism-based fermentations for the production of many specialty chemicals. I5 11-[531 The product of interest may be produced by either an extracellular or intracellular process relative to the microorganisms. In either of these situations, one of the key steps is the efficient removal of microorganisms or cell debris from the fermentation br~th.[~~][~~] In biotechnology terminology, this step, where cells are separated from the soluble components of the broth, is described as cell harvesting. Filtration is often preferred over centrifugation due to problems associated with poor separation which results in either reduced product yield or purity. Aerosol generation during centrifugation could be a major problem. This can be alleviated in the CFF mode due to the closed nature of system operation. Additionally, centrifuges may require high energy inputs since there is no appreciable density difference between the bacterial cell walls and the surrounding medium. Pre-coat filtration, when applicable, will suffer from reduced product yield and lower filtration rates (e.g., 0.7 to 16 L/hr-m2).[52]