Membrane module for substance-specific fluid treatment

Details Membrane module for substance-specific fluid treatment Membrane module for substance-specific fluid treatment

1999-06-25

2003-04-08

Kim, John (Department: 1723)

Liquid purification or separation

Processes

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

C210S651000, C210S805000, C210S321840, C210S321850, C210S321890

Reexamination Certificate

active

06544423

ABSTRACT:

BACKGROUND OF INVENTION
The invention relates to an apparatus for substance-specific treatment of a fluid, including
a) a housing,
b) an inlet arrangement for introducing the fluid to be treated into a distribution space in the housing,
c) an outlet arrangement for removing the treated fluid from a collection space in the housing,
d) at least one first treatment element and at least one second treatment element for substance-specific treatment of the fluid, where each treatment element has an end pointing toward the inlet arrangement and an end pointing to ward the outlet arrangement,
whereby the at least one first treatment element has at least one cavity formed by its walls, open toward the inlet arrangement and closed toward the outlet arrangement, and the at least one second treatment element has at least one cavity formed by its walls, open toward the outlet arrangement and closed toward the inlet arrangement; a process for substance-specific treatment of a fluid; and use of the apparatus.
Fluids in the context of the present invention are understood to be gases, gas mixtures, gases containing particles, and generally liquids such as clear solutions or suspensions.
Substance-specific treatments of fluids are becoming increasingly significant for applications such as biotechnology, medicine, or chemical technology. An example 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 fluids, 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 classs-pecific 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.
Substance-specific treatments in the context of the present invention are also understood to be those treatments via which molecules or particles are separated or retained due to their size. For a number of applications, it is desirable or necessary to subject a fluid to be treated to several, possibly different substance-specific treatments. In the case of filtration processes of suspensions with differing particle fractions, it is practical to first prefilter larger particles with a coarse, open-pored prefilter and then to subject the filtrate to further substance-specific treatment, according to size or to affinity for a ligand, for example.
In so-called “downstream processing”, such as further processing of biotechnically generated substances like proteins or biomolecules, several process stages for substance separation are conducted in series in order to isolate with optimum efficiency a certain target substance, such as an enzyme, from a prefiltered cell suspension. In this case, virus filtration stages are also employed in series with chromatographic stages. In other separation methods, anionic adsorbers are used sequentially with cationic adsorbers, or ionic adsorbers sequentially with hydrophobic adsorbers. Frequently, certain sizes of particle-shaped components, such as of a precipitate, must be retained from a suspension to be treated before the target substance is obtained in at least one chromatographic separation stage.
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 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 times 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 in many cases 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. Making the flow between the particles more uniform could probably be achieved by using spherical particles with as uniform a diameter as possible, but the production of such uniform particles is complex.
The cited disadvantages of particle-based 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 high 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 ra

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