Membrane module with layered hollow-fiber membranes

Details Membrane module with layered hollow-fiber membranes Membrane module with layered hollow-fiber membranes

1999-06-25

2001-04-10

Drodge, Joseph W. (Department: 1723)

Liquid purification or separation

Processes

Liquid/liquid solvent or colloidal extraction or diffusing...

C210S805000, C210S321750, C210S321760, C210S321790, C210S321800, C210S321840, C210S321850, C210S321890, C210S500230

Reexamination Certificate

active

06214232

ABSTRACT:

BACKGROUND OF THE INVENTION
The invention relates to an apparatus for substance-specific treatment of a fluid, comprising
a) a housing,
b) an inlet arrangement, connected to a distribution space, for introducing the fluid to be treated into the housing
c) an outlet arrangement, connected to a collection space, for removing the treated fluid from the housing, and
d) an arrangement of first hollow-fiber membranes and second hollow-fiber membranes,
whereby the hollow-fiber membranes are substantially parallel to each other and the hollow-fiber membranes have an end facing the distribution space and an end facing the collection space, whereby the first hollow-fiber membranes have cavities formed by their walls, open in the direction of the distribution space and closed in the direction of the collection space, and at least at the end facing the distribution space are embedded in a sealing compound that is joined in a fluid-tight manner with the wall of the housing, and whereby the second hollow-fiber membranes have cavities formed by their walls, open in the direction of the collection space and closed in the direction of the distribution space, and at least at the end facing the collection space are embedded in a sealing compound that is joined in a fluid-tight manner to the wall of the housing.
Substance-specific treatments of fluids are becoming increasingly significant for applications such as biotechnology, medicine, or chemical technology. Fluids include gases, gas mixtures, and generally 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, such as affinity chromatography, 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 high pressure drops of the particle column and 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 are described in U.S. Pat. No. 5,019,270. These consist of rigid, porous particles through which convective flow is possible. As a result of the convective substance transport through the particles and the non-compressibility, reduced residence time and increased productivity are possible compared to the previously mentioned column material.
While it is an advantage of chromatographic columns filled with such particles that their construction and use are simple, they have a number of disadvantages, one of which, aside from those discussed for sepharose particles, is that, particularly with larger-diameter chromatographic columns, the flow through the bulk particle material is not uniform, having a negative effect with respect to the uniform use of all the ligands present in the chromatographic column. Furthermore, technical control of the pressure required becomes increasingly complex as the diameters increase.
The cited disadvantages of particle-shaped carrier materials led to the development of a number of methods for substance-specific treatment of fluids, in which membranes with a porous structure are used as carrier materials for interacting groups. 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 passing 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).
Adaptation to the requirements of the treatment method can be attained via the type of the membrane used. Membranes are available in the form of hollow fibers or as flat membranes made from a wide variety of materials, so that adaptation to the physico-chemical properties of the fluids to be treated is possible. In addition, the pore size of the membranes can be adjusted such that a fluid to be treated, containing a target substance, for example, can pass through the membrane convectively, and—in the case of binding of the target substance to the interacting groups—there is no blockage of the membrane.
For a given linear flow rate, the thickness of the membrane wall can influence the residence time in the membrane of the fluid to be treated and the pressure drop during flow. Due to the generally thin walls (<300 &mgr;m, for example), membranes are distinguished by short transport distances of the fluid to be treated to interacting groups immobilized in the membranes, for example, resulting in relatively short residence times, low pressure drops, high linear flow rates, and thus high binding rates.
A number of apparatus 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 to be treated flows as a feed stream parallel to one side of the membrane, and a portion of the feed stream passes as a permeate through the membrane. Thus, in cross-flow modules, it is always only a portion of the liquid to be treated that passes through the membrane, namely the portion that passes through the membrane wall as a permeate and can be

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