Cross-flow filtration downstream processing

The advantage of single-pass over cross-flow filtration is that it is an easier system to operate and can be cost effective, particularly if the product to be filtered is expensive, because very tittle of the initial fluid is lost during filtration. However, because the flow pattern of the fluid is directly through the filter, filter life maybe too short for the fluid being filtered. The minimum flow rate needed downstream of the filter must also be considered, especially when there are time constraints to the process. In some situations it may be more advantageous to use a cross-flow system where higher flow rates may be easier to obtain. 

Microfiltration is a unit operation for the separation of small particles. The separation limits are between 0.02 and 10 (jum particle dimensions. Microfiltration can be carried out in a dead-end mode and a cross-flow mode. In downstream processing, the cross-flow filtration is carried out continuously or discontinuously. The most important parameters that determine the productivity of cross-flow microfiltration are transmembrane pressure, velocity, particle size and surface, viscosity of the liquid and additives such as surfactants, and changing the surface and surface tension. 

Although this technique is not limited to the initial cell recovery stages of a downstream process, cross-flow filtration is commonly used for product recovery operations, particularly in lower volume processes where stringent hygiene requirements apply, as in the pharmaceutical and food industries. 

Clarification, or harvest, is typically the first step in downstream processing. During clarification, the cells, cell debris, and other particulates are removed from the cell culture broth, which contains the product. Clarification can be accomplished by depth filtration or by centrifugation followed by some form of filtration. Tangential flow filtration (ITT), sometimes also referred to as cross-flow filtration (CFF) is also used for clarification. Tangential flow filters are designed either in a flat sheet mode or hollow fiber mode. 

Kroner KH, Schiitte H, Hustedt FI et al. (1984) Cross-flow filtration in the downstream processing of enzymes. Proc Biochem 19(2) 67-74... 

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