Tangential flow filtration applications

When CMP was first emerging as an important process, microporous membranes were tested in a tangential flow filtration (TFF) mode. In typical CMP slurries, TFF was found to be unacceptable due to the high solids content. Also, there was insufficient control of the retentate build-up on the membrane face, called concentration polarization. TFF works best with applications that have lower solids and a greater spread between retained and passed species. The excessive polarization we observed with high solids silica slurries prevented useful fractionation. TFF may be useful for the newer slurries with low solids content. Three critical questions to any filter design in slurry applications are (i) how sharp can the filtration curve be to enable clean fractionation, (ii) how is retained material handled to control filter life, and (iii) how does media selection affect the above two points. 

Membrane operations are conducted either in a direct flow filtration (also called dead end) mode or in a tangential flow filtration (TFF) mode. Direct flow filtration is simple and easy to implement but has limited capacity for applications with high-solid mass. TFF is capable of processing large-solid masses but is more complex and capital intensive. 

Applications Of Tangential Flow Filtration In Cell Separation... 

Currently, there are many examples of cell processing in the industrial environment using tangential flow filtration. To illustrate the breadth of microbial types which may be processed by this technology, we will discuss three applications which have been in routine operation under production conditions. The applications include cell/growth medium separations directly from fermentors (Escherichia coli and Mycoplasma species) and the concentration/washing of influenza virus used in the production of flu vaccines. 

All three of these applications are examples of commercial processes using tangential flow filtration. Clearly, the selection of... 

It was the object of this presentation to outline some of the key parameters which are evaluated during the application of tangential flow filtration for cell separations. A throrough understanding of what is required from the separation is an essential first step. 

Cross-flow filtration (CFF) also known as tangential flow filtration is not of recent origin. It began with the development of reverse osmosis (RO) more than three decades ago. Industrial RO processes include desalting of sea water and brackish water, and recovery and purification of some fermentation products. The cross-flow membrane filtration technique was next applied to the concentration and fractionation of macromolecules commonly recognized as ultrafiltration (UF) in the late 1960 s. Major UF applications include electrocoat paint recovery, enzyme and protein recovery and pyrogen removal. 

The unique features of tangential-flow filtration include the ability to remove cells and cell debris from the growth medium, which contains the product of interest, to concentrate the product of interest and to fractionate solutes of different size. These features have lead to numerous applications of tangential flow filtration in the purification of protein products. These same features could be exploited both for virus purification and validation of vims clearance as described in the following sections. 

Table 20.1 summarizes some of the important vimses for gene therapy applications and viral vaccines that have been purified using tangential-flow filtration. Vimses can be divided into two groups enveloped and nonenveloped. Enveloped vimses contain an outer lipoprotein bilayer membrane derived from the membranes of the host ceU. Nonenveloped vimses lack this outer lipoprotein membrane. 

Samples with particulate matter may present quite serious problems, and it may be desirable to remove particles, for example, by centrifugation, and examine this fraction by procedures applicable to solid phases which are discussed in Section 2.2.5. Tangential-flow high-volume filtration systems have been used for analysis of particulate fractions (>0.45 jum) where the analytes occur in only low concentration (Broman et al. 1991). Attention has already been drawn to artifacts resulting from reactions with cyclohexene added as an inhibitor to dichloromethane. It has also been suggested that under basic conditions, Mn2+ in water samples may be oxidized to Mn(III or IV) which in turn oxidized phenolic constituents to quinones (Chen et al. 1991). Serious problems may arise if mercuric chloride is added as a preservative after collection of the samples (Foreman et al. 1992) since this has appreciable solubility in many organic solvents, and its use should therefore be avoided. 

Cross-flow (tangential) filtration is finding increased interest and application in winemaking and juice/concentrate production. The process uses membranes of various porosities, depending on application. 

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