Ultrafiltration membrane principle

Cross-flow is the usual case where cake compressibility is a problem. Cross-flow microfiltration is much the same as cross-flow ultrafiltration in principle. In practice, the devices are often different. As with UF, spiral-wound membranes provide the most economical configuration for many large-scale installations. However, capillary devices and cassettes are widely employed, especially at smaller scale. A detailed description of cross-flow microfiltration had been given by Murkes and Carlsson [Crossflow Filtration, Wiley, New York (1988)]. 

Fig. 6.2 The principle of micellar catalysis and the recycling of the catalytic active micelles by (a) using an extracting solvent or (b) an ultrafiltration membrane.

This chapter will focus on three types of membrane extracorporeal devices, hemodialyzers, plasma filters for fractionating blood components, and artificial liver systems. These applications share the same physical principles of mass transfer by diffusion and convection across a microfiltration or ultrafiltration membrane (Figure 18.1). A considerable amount of research and development has been undertaken by membrane and modules manufacturers for producing more biocompatible and permeable membranes, while improving modules performance by optimizing their internal fluid mechanics and their geometry. 

In principle the time could be reduced further by forcing the solution through an ultrafiltration membrane under pressure but we have no experience of the application of this method to oligonucleotides. Ultrafiltration could also be used for concentrating oligonucleotide solutions. 

The method of thermoporometry, developed by Brun, Lallemand, Quinson and Eyraud( ), represents another method applicable, at least in principle, to characterization of pore volume in ultrafiltration membranes (, ). However, for asymmetric membranes, pore volumes explored by thermoporometry may not be the volumes associated with membrane skins and "functional" pores. 

Compared to batch processes, continuous processes often show a higher space-time yield. Reaction conditions may be kept within certain limits more easily. For easier scale-up of some enzyme-catalyzed reactions, the Enzyme Membrane Reactor (EMR) has been developed. The principle is shown in Fig. 7-26 A. The difference in size between a biocatalyst and the reactants enables continuous homogeneous catalysis to be achieved while retaining the catalyst in the vessel. For this purpose, commercially available ultrafiltration membranes are used. When continuously operated, the EMR behaves as a continuous stirred tank reactor (CSTR) with complete backmixing. For large-scale membrane reactors, hollow-fiber membranes or stacked flat membranes are used 129. To prevent concentration polarization on the membrane, the reaction mixture is circulated along the membrane surface by a low-shear recirculation pump (Fig. 7-26 B). 

Figure 15.3 (a) Principle of construction of (A) artificial kidney and (B) artificial bladder (1) flow of blood, (2) flow of ultrafiltrate, (3) plasma-filtrating membrane, (4) adsorbing material, (5) ultrafiltration membrane, (b) Reasonable disposition of the artificial kidney (A) artificial kidney, (B) artificial bladder, (C) artificial ureter, (D) Implanted arteries and venous canulas. (Reprinted from [356] with permission of Elsevier.)... 

A different approach of major practical importance is the separation of polymer-bound catalysts from low molecular weight products and substrates by means of appropriate nano- or ultrafiltration membranes. For porous membranes, the larger size of the dissolved macromolecules, which prevents permeation through the pores, can be regarded as the underlying principle. In nonporous membranes, the solubility of the macromolecules in the membrane material in combination with the diffusion coefficent can be considered as the physical basis. The unit operations for membrane separation are discussed in the following Section 7.3.2. 

Ultrafiltration is a membrane process whose nature lies between nanofiltration and microfiltration. The pore sizes of the membranes used range from 0.05 um (on the microfiltration side) to 1 am (on the nanofiltration side). Ultrafiltration is typically used to retain macromolecules and colloids from a solution, the lower limit being solutes with molecular weights of a few thousand Daltons. Ultrafiltration and microfiltration membranes can both be considered as porous membranes where rejection is determined mainly by the size and shape of the solutes relative to the pore size in the membrane and where the transport of solvent is directly proportional to the applied pressure. Such convective solvent flow through a porous membrane can be described by the Kozeny-Carman equation (see eq. VI - 27) for example. In fact both microfiltration and ultrafiltration involve similar membrane processes based on the same separation principle. However, an important difference is that ultrafiltration membranes have an asymmetric structure with a much denser toplayer (smaller pore size and lower surface porosity) and consequently a much higher hydrodynamic resistance. 

Membrane Filtration. Membrane filtration describes a number of weU-known processes including reverse osmosis, ultrafiltration, nanofiltration, microfiltration, and electro dialysis. The basic principle behind this technology is the use of a driving force (electricity or pressure) to filter... 

Fig. 5-17. Principle of micellar-enhanced ultrafiltration (MEUF). The d-enantiomer of a racemic mixture is preferentially bound to the micelles, which are retained by the membrane. The bulk containing the 1-enantiomer is separated through the membrane [72].

In bioprocesses, a variety of apparatus that incorporate artificial (usually polymeric) membranes are often used for both separations and bioreactions. In this chapter, we shall briefly review the general principles of several membrane processes, namely, dialysis, ultrafiltration (UF), microfiltration (MF), and reverse osmosis (RO). 

The principles behind ultrafiltration are sometimes misunderstood. The nomenclature implies that separations are the result of physical trapping of the particles and molecules by the filter. With polycarbonate and fiberglass filters, separations are made primarily on the basis of physical size. Other filters (cellulose nitrate, polyvinylidene fluoride, and to a lesser extent cellulose acetate) trap particles that cannot pass through the pores, but also retain macromolecules by adsorption. In particular, these materials have protein and nucleic acid binding properties. Each type of membrane displays a different affinity for various molecules. For protein, the relative binding affinity is polyvinylidene fluoride > cellulose nitrate > cellulose acetate. We can expect to see many applications of the affinity membranes in the future as the various membrane surface chemistries are altered and made more specific. Some applications are described in the following pages. 

We can use the same filtration principle for the separation of small particles down to small size of the molecular level by using polymeric membranes. Depending upon the size range of the particles separated, membrane separation processes can be classified into three categories microfiltration, ultrafiltration, and reverse osmosis, the major differences of which are summarized in Table 10.2. 

W. Eykamp, Microfiltration and Ultrafiltration, in Membrane Separation Technology Principles and Applications, R.D. Noble and S.A. Stem (eds), Elsevier Science, Amsterdam, pp. 1-40 (1995). 

Figure 7.4 Membrane pore diameter from bubble point measurements versus Bacillus prodigiosus concentration [1], Reprinted from W.J. Elford, The Principles of Ultrafiltration as Applied in Biological Studies, Proc. R. Soc. London, Ser. B 112, 384 (1933) with permission from The Royal Society, London, UK...

Adsorbents are used in medicine mainly for the treatment of acute poisoning, whereas other extracorporeal techniques based on physico-chemical principles, such as dialysis and ultrafiltration, currently have much wider clinical applications [1]. Nevertheless, there are medical conditions, such as acute inflammation, hepatic and multi-organ failure and sepsis, for which mortality rates have not improved in the last forty years. These conditions are usually associated with the presence of endotoxin - lipopolysaccharide (LPS) or inflammatory cytokines - molecules of peptide/protein nature [2]. Advantages of adsorption over other extracorporeal techniques include ability to adsorb high molecular mass (HMM) metabolites and toxins. Conventional adsorbents, however, have poor biocompatibility. They are used coated with a semipermeable membrane of a more biocompatible material to allow for a direct contact with blood. Respectively, ability of coated adsorbents to remove HMM solutes is dramatically reduced. In this paper, preliminary results on adsorption of LPS and one of the most common inflammatory cytokines, TNF-a, on uncoated porous polymers and activated carbons, are presented. The aim of this work is to estimate the potential of extracorporeal adsorption technique to remove these substances and to relate it to the porous structure of adsorbents. 

Blatt, WF, Principles and practice of ultrafiltration, in Meares, P, Ed., Membrane Separation Processes, Elsevier Science, Amsterdam, 1976. 

In principle, ultrafiltration can be an easy way to quantify free drug fraction present in plasma, serum, or other biological fluids. The approach is not without pitfalls, however, in that ion suppression, clogged membranes, and poor sensitivity due to extensively bound drugs can derail this type of assay. Still, ultrafiltration has a lot of untapped potential and could become pervasive as membranes are made more robust and adapted to high-throughput formats such as 96-well plates. A related sample preparation technique, microdialysis, is discussed in Chapter 12. 

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