Liquid purification or separation – Processes – Liquid/liquid solvent or colloidal extraction or diffusing...
Reexamination Certificate
1999-12-14
2001-08-07
Fortuna, Ana (Department: 1723)
Liquid purification or separation
Processes
Liquid/liquid solvent or colloidal extraction or diffusing...
C210S638000, C210S321790, C210S321800, C210S500230, C210S502100
Reexamination Certificate
active
06270674
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to a membrane module for substance-specific treatment of a fluid, comprising
a) a housing with a longitudinal extent, and
b) therein, arranged substantially in the direction of the longitudinal extent of the housing, a bundle of hollow-fiber membranes with a semipermeable wall having a porous structure.
BACKGROUND
Substance-specific treatments of fluids are becoming increasingly significant for applications such as biotechnology, medicine, and chemical technology. Fluids include gases, gas mixtures, and liquids such as protein solutions, prefiltered suspensions, and clear solutions. An example of substance-specific treatment is the extraction of active agents from cell suspensions in which genetically modified cells have generated substances such as antibodies, hormones, growth factors, or enzymes, usually in small concentrations. Other important applications are the extracorporeal removal of undesired substances from human blood plasma and extraction of components such as immunoglobulins or clotting factors from the plasma of donated blood. Finally, another broad application area is the catalytic or biocatalytic—enzymatic—treatment of liquids, such as the hydrolysis of oils by lipases immobilized in a matrix.
The substance-specific treatment of fluids is frequently conducted such that the fluid to be treated is brought into contact with a carrier material, on and/or in which interacting groups or substances are immobilized that, in a specific, selective manner, interact with the target substance contained in the fluid, i.e., with the substance that is the object of the substance-specific treatment. Such interactions can be, for example, cationic or anionic exchange, hydrophilic/hydrophobic interaction, hydrogen bridge formation, affinity, or enzymatic or catalytic reactions, and the like. In affinity separation of substances, ligands are coupled to or immobilized in the carrier material and have the function of adsorptively binding a specific single target substance or an entire class of substances. This target substance is termed a ligate. One example of class-specific ligands are positively charged diethylaminoethyl (DEAE) groups or negatively charged sulfonic acid (SO
3
) groups, which adsorb the class of positively charged or negatively charged molecules, respectively. Specific ligands are, for example, antibodies against a certain protein, which is bound as a ligate to the antibody.
The major criteria in the substance-specific treatment of fluids are productivity and selectivity. With a view toward productivity, it is important that, per unit of volume, as many groups as possible are available that act in a substance-specific manner and can interact with the target substance contained in the fluid to be treated. At the same time, it is desirable to maximize the transport of the target substance to the groups or substances acting in a substance-specific manner.
One carrier material for ligands that is frequently employed in affinity chromatography is sepharose particles, which are present in bulk form in a chromatographic column. Even if a high concentration of ligands, with high selectivity, can be realized in this case, the productivity is known to be low due to the compressibility of the sepharose particles. Furthermore, the access of the ligates to the ligands contained in the sepharose particles is diffusion controlled, which results in long residence times and thus low throughput and productivity, in particular when separating larger molecules such as proteins, due to their low diffusion rates.
Improved chromatographic column materials made from rigid, porous particles through which convective flow is possible are described in U.S. Pat. No. 5,019,270. Compared to the previously cited column material, these particles permit a reduction of residence time and increased productivity. However, even chromatographic columns filled with these particles exhibit with larger-diameter column diameters a non-uniform flow rate that has a negative effect with respect to the uniform utilization of all the ligands present in the chromatographic column. Furthermore, technical control of the pressure required becomes more complex as the diameters increase.
The cited disadvantages of particle-shaped carrier materials led to the development of a number of processes for substance-specific treatment of fluids using porous, semipermeable membranes. Due to their porous structure, membranes present a large inner surface area, so that a large number of functional groups can be coupled to the membrane, in high concentration per volume unit, which can interact with the fluids to be treated that flow through the membrane (see, for example, E. Klein, “Affinity Membranes”, John Wiley & Sons, Inc., 1991; S. Brandt et al., “Membrane-Based Affinity Technology for Commercial Scale Purifications”, Bio/Technology Vol. 6 (1988), pp. 779-782).
Membranes are available that are made from a wide variety of materials and with varying pore structures, so that adaptation to the physico-chemical properties of the fluids to be treated and convective transport through the membrane of the fluid to be treated, for example with a target substance contained therein, is possible. Moreover, due to the generally thin walls (<100 &mgr;m, for example), membranes are distinguished by short transport distances of the fluid to be treated to, for example, the interacting groups immobilized in the membranes, resulting in relatively short residence times, low pressure losses, high linear flow rates, and thus high binding rates.
A number of modules containing such membranes have been described that are used in processes for substance-specific treatment of fluids. In this case, a distinction must be drawn between so-called dead-end mode, or dead-end modules, and cross-flow mode, or cross-flow modules.
In the cross-flow mode, the fluid flows as a feed stream parallel to one side of the membrane. A portion of the feed stream thereby passes through the membrane. The partial stream after passing through the membrane is drained off as a permeate, and the portion remaining on the feed stream side as a retentate. On the permeate side of the membrane as well, an additional fluid stream can be introduced that then absorbs the partial stream after it passes through the membrane.
In dead-end mode, on the other hand, the entire fluid entering the membrane module as a feed stream is directed through the membrane and removed as a filtrate or permeate from the downstream side of the membrane opposite the upstream side.
Dead-end membrane modules on the basis of hollow-fiber membranes are used extensively for applications in the fields of ultra- or microfiltration and often for treatment of liquids with gases, for example. In one part of these membrane modules, as described in EP-A-0,138,060 or EP-A-0,659,468; for example, the hollow-fiber membranes have been folded in a U-shape and their ends embedded jointly in a sealing compound and open. The gas or liquid to be filtered flows, for example, via the open ends into the lumina of the hollow-fiber membranes and, due to the prevailing pressure differential, permeates into the external space surrounding the hollow-fiber membranes. In the case of filtration applications, the component that is filtered out remains in the membrane.
In another embodiment of dead-end membrane modules, the hollow-fiber membranes are arranged substantially linearly in the housing and their open ends are embedded jointly in a sealing compound, while their other ends are free, i.e., not embedded. The unembedded ends of the hollow-fiber membranes are closed in these modules. Such membrane modules are described in U.S. Pat. No. 4,002,567, U.S. Pat. No. 4,547,289, EP-A-0,138,060, or EP-A-0,732,142, for example.
All dead-end membrane modules have a disadvantage in that they are often not suited for the treatment of suspensions, for example, when the size of the particles contained in the suspension is on the order of magnitude of the pore diameter. The particles would lead to the f
Baurmeister Ulrich
Wollbeck Rudolf
Akzo Nobel nv
Fortuna Ana
Oliff & Berridg,e PLC
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