Abstract:
A filter module includes a first filter stage and a second filter stage which are substantially concentrically arranged. The first filter stage and the second filter stage each include a plurality of hollow fiber membranes having a first fiber end and a second fiber end, which are embedded in a respective casting compound. The first filter stage is a filter stage for the filtration of a first medical fluid, and the second filter stage is a filter stage for the filtration of a second medical fluid. The first filter stage has unilaterally closed fiber ends, and is surrounded by a boundary element which separates the first filter stage and the second filter stage from one another. The boundary element has at least one opening which provides fluid communication between the first filter stage and the second filter stage.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. provisional application No. 61/457,957, filed Jul. 18, 2011, and priority of German number 10 2011 107 980.0 filed Jul. 18, 2011, hereby incorporated by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of Invention 
     The present invention relates to a filter module and to a method of manufacturing a hollow fiber membrane bundle having at least two concentrically arranged filter stages. The invention in particular relates to filter modules for hemodialysis, in particular to filter modules which integrally contain a plurality of filtration stages. 
     2. Description of the Prior Art 
     A plurality of filters are required for a number of therapeutic processes of extracorporeal blood purification. In these processes, blood is as a rule filtered or dialyzed at hollow fiber membranes of a filter module for purifying toxic metabolites. High demands are made in this respect on the fluids used for substitution or for dialysis to be able to be used in the therapeutic processes. Such fluids are provided in pouches licensed under drug law or are manufactured online by the extracorporeal blood treatment machines. To be able to ensure the microbiological purity in the online processes, these fluids have to run through one or two filtration stages before they may be used as replacement fluids in dialysis or as substitution fluids in blood filtration processes. 
     There have previously been endeavors to design the fluid circuits of extracorporeal blood treatment circuits more compact and to integrate them for disposable articles. Cassette systems for extracorporeal blood treatment have in particular been developed for which a plurality of functions for blood treatment and fluid treatment are integrated. 
     Developments have equally been promoted in the field of blood filters using hollow fiber membranes in which a plurality of filter stages have been integrated in a filter module. 
     EP 0 791 368 A2 shows a two-stage filter module for hemodiafiltration. In a first stage, inflowing substitution fluid penetrates into the interior of the hollow fiber membrane, is filtered in so doing and is mixed with blood in a blood chamber at the head end of the filter module. In a second stage, the diluted blood runs through the interior of the hollow fiber membranes and is dialyzed and filtrated in so doing. 
     DE 39 01 446 A1 describes a two-stage filter having a first stage in which dialysis fluid is directed into the interior of the hollow fiber membranes, passes through the membrane and is filtered in so doing. The filtrate of the first stage is directly directed into the second stage and there flows through the outer space of the hollow fiber membrane bundle as dialysis fluid. 
     DE 33 26 704 A1 shows a two-stage filter module in which the hollow fiber membrane bundles are concentrically arranged. Blood is filtered in an inner first filtration stage. In the second, surrounding filtration stage, blood is treated in substance exchange with dialysis fluid. 
     SUMMARY OF THE INVENTION 
     It is therefore the object of the present invention to further develop in an advantageous manner a filter module and a method of manufacturing a hollow fiber membrane bundle having two concentrically arranged filter stages, in particular such that the setup of a medical fluid circuit can be simplified using the filter module. 
     This object is achieved in accordance with the invention by a filter module having at least one first filter stage and at least one second filter stage is manufactured comprising and/or consisting of hollow fiber membranes which are arranged substantially concentrically, wherein the fiber ends of the hollow fiber membranes are embedded at least partly and/or at least unilaterally in a casting compound, wherein the first filter stage is a filter stage for filtration of a first medical fluid and the second filter stage is a filter stage for filtration of a second medical fluid, wherein the first filter stage has closed fiber ends at one side, wherein a bounding means surrounding the first filter module is provided which separates the first filter stage and the second filter stage at least partly from one another and has at least one opening which establishes a filter communication between a first filter stage and a second filter stage. 
     The advantage thereby results that an integrated arrangement of an ultrafilter and a blood filter can be achieved in a single filter housing of a filter module. The advantage hereby in particular results that a cost reduction can be achieved by lower material use since now two to three filters can be integrated for a single filter or the function of two to three filters can be achieved by a single filter module. 
     It is furthermore possible to use an extruded housing, whereby a cost reduction can be achieved in comparison with injection molding manufacturing processes. It is furthermore possible by a simplified setup which results from the filter module in accordance with the invention to simplify the setup of a blood treatment apparatus such as a dialysis machine overall, for instance such that fewer valves, hoses or less electronics or software is/are required or is/are required in less complex form. An advantage furthermore results in that the filter module can be designed completely as a disposable article, that is as a so-called disposable, whereby overall a higher security can be achieved by individual product tests in production before each use at lower costs. It is in particular no longer necessary to perform a reuse of sterile filters on the dialysis side of a blood treatment apparatus such as a dialysis machine. 
     It is furthermore possible to achieve a reduction of test times during dialysis, for which purpose filter integrity tests have previously had to be used since the sterile filters on the dialysis side are reused. A higher dialysis dosage for the patient can hereby be achieved. In addition, it is possible to achieve a higher dialysis dosage with an unchanged area flowed through by blood since a better dialysate distribution can be achieved by means of the filter module in accordance with the invention. 
     Provision can be made that the first medical fluid is a dialyzing liquid and/or a substitution fluid and/or that the second medical fluid is blood and/or that the first filter stage is surrounded by the second filter stage. Provision can be made in this respect that the first filter stage is designed in the form of a substantially cylindrical hollow fiber bundle, whereas the second filter stage is designed in the form of a hollow cylindrical hollow fiber bundle in which the first filter stage is arranged. 
     Provision is in particular made that the second filter stage in each case has unclosed fiber ends at both sides. 
     It is furthermore possible that the boundary means has and/or forms a boundary wall and that the opening in the boundary means is arranged in the boundary wall in the region adjacent to the casting compound and/or that the boundary means has at least one venting opening. Openings in the boundary wall in the region adjacent to the casting compound can be arranged peripherally in the boundary wall, e.g. by perforating and/or piercing this section of the boundary wall. A uniform transition of the filtrate into the second filter stage and an optimized onflow of the fibers in the second filter stage thus takes place at the periphery of the first filter stage. A venting opening which is preferably designed with an opening smaller in comparison with the opening arranged in the boundary means is in particular sensible when the filter module is set slightly slanted, with the blood entry side being somewhat higher. The venting of the filter module is hereby facilitated. Since, however, a small quantity of dialysate can flow directly to the dialysate outlet during operation, whereby the performance might be negatively influenced, it is expedient to provide a comparatively small opening as a venting opening. It is generally also conceivable that a plurality of openings are provided in the boundary means, with the openings being arranged running around the periphery of the boundary means. It hereby becomes possible to achieve a particularly uniform distribution of the dialysate so that the second filter stage is flowed about by dialysate uniformly on its outer side. 
     It is possible that the boundary means is or comprises a film and/or a tube. 
     Provision can furthermore be made that the opening in the boundary means is formed from one or from a plurality of openings arranged peripherally at the boundary means, with the openings preferably being peripherally arranged slits, perforations, holes, labyrinth slits or the like. 
     Provision can furthermore be made that the filter module has a first end cap in which a connection to the first filter stage and a connection to the second filter stage is arranged, with the fiber ends of the first filter stage being unclosed on the side of the first end cap and with at least one sealing element being provided by means of which the unclosed fiber ends of the first filter stage can be and/or are sealed from the connection to the second filter stage and from the second filter stage. 
     It is furthermore possible that the filter module has a second end cap in which a connection to the second filter stage is arranged and/or that the fiber ends of the first filter stage are closed on the side of the second end cap. 
     Provision can moreover be made that the filter module has a housing in which the filter stages are arranged, with at least one connection to the first filter stage being arranged in the housing. 
     A connection can generally be an inflow to or an outflow to a filter stage since it is generally possible to operate the filter module in both the one and in the other fluid direction, that is to have a fluid flow through the filter stages both in the one direction and in the other direction. 
     Provision can furthermore be made that at least one passage element is provided concentrically and coaxially to the longitudinal axis of the filter module and/or to the filter stages, said passage element being connected to the second filter stage, and/or that at least one passage element is provided at the outer side of the filter module and is connected to the second filter stage. 
     It is furthermore conceivable that the filter module has at least one pump element and/or can be connected to at least one pump element, by means of which the first and/or second medical fluid can be pumped. 
     Provision can moreover be made that the pump element is a pump element integrated into the filter module and/or that the pump element is an impeller pump. 
     It is furthermore possible that a third filter stage is provided, with the first filter stage and the third filter stage being arranged with respect to one another such that the first medical fluid can be introduced from the first filter stage into the third filter stage via and/or through the hollow fiber membranes of the first and third filter stages. 
     It is furthermore conceivable that the first, second and third filter stages are arranged concentrically and coaxially, with the first filter stage surrounding the third filter stage and the second filter stage surrounding the first filter stage. 
     Provision can moreover be made that the filter module has a first end cap into which a connection to the first filter stage and a connection to the second filter stage is arranged, with the fiber ends of the first filter stage being unclosed on the side of the first end cap and with at least one sealing element being provided by means of which the unclosed fiber ends of the first filter stage can be and/or are sealed from the inflow to the first filter stage and from the second filter stage, with the fiber ends of the third filter stage being closed on the side of the first end cap, with a second end cap being provided in which a connection of the third filter stage is arranged and with the fiber ends of the third filter stage being unclosed on the side of the second end cap. 
     Provision can furthermore be made that at least one pump element can be and/or is connected to the connection to the third filter stage, with the pump element preferably being an integrated pump element and/or with the connection to the third filter stage being connectable and/or connected to the third filter stage using a connection to the second filter stage. 
     The present invention furthermore relates to a method of manufacturing a hollow fiber membrane bundle having two concentrically arranged filter stages. The method includes at least the following steps:
         surrounding a first hollow fiber membrane bundle for a first filter stage in a film, tube film and/or a tube;   embedding the first filtration stage in hollow fibers of the second filtration stage;   molding the first and second filtration stage by a casting compound in a molding process;   cutting off an end region of the casting compound, including closed fiber ends, for exposing and laying open all fiber ends; and   closing a fiber end side of the first filtration stage by thermal influence and melting the fiber end side and the casting compound.       

     Processes for molding hollow fiber bundles are known in the prior art, e.g. for instance from JP 06-006156. The fiber ends first have to be closed so that no casting mold can penetrate into the fiber. This is already done by smelting processes with thermal effect on the fiber ends, e.g. by laser irradiation, heat mirrors or hot stamps. Subsequently, the casting takes place with a hardening castable compound, e.g. polyurethane materials, so that the fiber ends are closed except for some centimeters by the casting compound. Subsequently a cut takes place through the casting compound at the outer end of the fiber ends so that the closed fiber ends embedded in the casting compound are cut off. The fiber bundle cast at the end and now having open fiber ends remains. 
     To close the ends of a filtration stage in the manufacturing process again as in the present invention, a further step of closing the hollow fiber ends has to take place. A filtration stage can be closed by melting the casting compound having fiber ends by a repeated geometrically precise application of heat on a zone of the hollow fiber bundle including a plurality of filtration stages. The heat application can take place, for example, by laser, heat mirror or hot stamp. 
     Provision can in particular be made that the closing of the fiber end side takes place by means of laser and/or hot stamp. 
     It is furthermore conceivable that a third filtration stage is formed in the first filtration stage, with a first region being closed on a fiber end side and with a second region being closed on the other fiber end side, with hollow fibers being closed in the first region and these hollow fibers being surrounded by the second region on the other fiber end side and being at least partly unclosed. 
     It can hereby be achieved that the fluid, e.g. the dialysate, first enters into the first filter stage on the one fiber end side and cannot enter into the third filter stage due to the closed fiber ends. A transition of the fluid from the first filter stage into the third filter stage can thus advantageously only take place via the membranes of the hollow fiber membranes of the first and third filter stages. Since the hollow fiber ends of the first filter stage are closed on the other fiber end side and the hollow fiber ends of the third filter stage are unclosed, the fluid cannot pass unfiltered, but must rather flow through the membranes. The fluid, e.g. a medical fluid such as dialysate, is hereby securely filtered. 
     It is possible that a third filtration stage is formed in the first filtration stage, with a first region being closed on one fiber end side and a second region being closed on the other fiber end side, with hollow fibers being closed in the first region and these hollow fibers being surrounded and at least partly unclosed on the other fiber end side and that the first region is circular and the second region is annular, with the inner diameter of the second region preferably being selected to be smaller than the outer diameter of the first region. The outlet diameter of the fiber bundle of the third filter stage is hereby made smaller, for example, than the core diameter of the molded or closed bundle on the entry side of the third filter stage. It is thus advantageously ensured that dialysate is always filtered in two stages before it e.g. is infused into the extracorporeal blood circuit as postdilution and/or predilution. It can thereby in particular be achieved that individual fibers which are unexpectedly obliquely disposed in the total bundle by the production do not project from the third filter stage into the first filter stage. A two-stage filtration can thereby be ensured simply, reliably and advantageously. 
     Provision can furthermore be made that, in at least one further step, a filter module as described herein is manufactured from the hollow fiber membrane bundle. 
     The present invention furthermore relates to a disposable element that includes at least one filter module as described herein, and that is or includes a disposable cassette. 
     Provision can furthermore be made that the disposable is and/or comprises a disposable cassette. 
     The present invention furthermore relates to a blood treatment apparatus that has at least one filter module and/or a disposable element as described herein. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Further details and advantages of the invention will now be explained in more detail with reference to an embodiment shown in the drawing. 
       There are shown 
         FIG. 1 : a schematic representation of a filter module through a section along the central axis of symmetry of the concentric fiber bundle; 
         FIG. 2 : a schematic plan view of the blood entry side; 
         FIG. 3 : a schematic plan view of the blood outlet side; 
         FIG. 4 : a further schematic representation of a filter module in a second embodiment through a section along the central axis of symmetry of the concentric fiber bundle; 
         FIG. 5 : a further schematic representation of a filter module in a third embodiment through a section along the central axis of symmetry of the concentric fiber bundle; and 
         FIG. 6  a further schematic representation of a filter module in a fourth embodiment through a section along the central axis of symmetry of the concentric fiber bundle; 
         FIG. 7 : a schematic plan view of the blood entry side; and 
         FIG. 8 : a schematic plan view of the blood outlet side. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. 
       FIG. 1  shows a schematic representation of a single-stage integrated ultrafilter as a first filter stage  20  in a filter module  10 , with only the upper half of the filter module  10  substantially radially symmetrical to the axis X being shown. 
     The core of the fiber bundle of the first filter stage  20  comprises the ultrafilter membranes  22 . They can be identical to the blood filter membranes  32  of the second filter stage  30 , but can also be adapted in membrane structure (high CUF for water; CUF=ultrafiltration coefficient) and dimensions (small inner diameter) to the object of the water filtration. 
     This fiber bundle  24  of the first filter stage  20  is surrounded by a boundary means  40  in the form of a tubular film or a tube which shows a housing having an outlet  44  at one side. The opening  44  can include a plurality of openings peripherally at the tube  40  so that a radially uniform transfer of the filtrate from the first filter stage  20  into the second filter stage  30  takes place. The dialysate enters at an end face through the connection  54  which is arranged in the end cap  50  and which is a dialysate inlet  54 , through the unclosed hollow fiber membrane ends  26  into the lumen of the first filter stage  20  which is an ultrafilter stage and is discharged through the wall into the inner region of the fiber bundle  24  since the ends  28  of the hollow fibers  22  of the first filter stage  20  are completely closed on the side of the second end cap  60 . 
     The fiber bundle  24  is sealed before closure, e.g. using a laser or hot stamp, on both end faces so that the ultrafilter membrane  22  of the first filter stage receive unilaterally closed fibers after the closing, that is in the end region  28 , whereas the end region  26  is unclosed. In order reliably to preclude a direct overflow of dialysate through individual fibers into the dialysate space or blood space, the entry diameter for the dialysate is somewhat smaller due to a sealing ring  70  than the outlet diameter (cf.  FIGS. 2 and 3 ). The sealing ring  70  lies on the ultrafilter fibers on the contact surface  72  and closes them. 
     The fiber module  10  is provided on the entry side with the especially designed end cap  50  in which the dialysate is supplied centrally via the connection  54  and the blood is supplied radially via the connection  52 . The dialysate outlet  82  is here located radially at the housing  80 . The arrows designate the flow direction D of the dialysate and the flow direction of the blood B. 
     The module is provided with a standard cap  60  having a central blood outlet  62  on the blood outlet side. It is generally also conceivable that the blood outlet is radially arranged. 
     Since the dialysate is discharged in the core of the fiber bundle  24 , a good dialysate distribution is possible without diameter enlargement of the housing at the ends. A simple tube is therefore conceivable as a housing which is either integrated into a cassette or was extruded in an inexpensive manner. 
     The filter module  10  should be operated while lying horizontally to ensure good venting on priming. The dialysate outlet  82  and the (radial) blood outlet should face upwardly. 
     Alternatively, the module can be set slightly obliquely, with the blood inlet side being somewhat higher. In this case, it is meaningful to provide the inner tube or the boundary means  40  which separates the ultrafilter  20 , that is the first filter stage, from the blood filter  30 , that is the second filter stage  30 , with a small venting opening  42  at the inlet side of the dialysate. A small amount of dialysate will here flow directly to the outlet during operation and the performance is negatively influenced. The opening should therefore preferably be kept very small. 
     The hollow fiber membranes  32  of the second filter stage  30  form a substantially hollow cylindrical fiber bundle  34  in which the bundle  24  is arranged. Both ends  36 ,  38  of the fiber bundle  34  are unclosed. 
     The fibers  32  for the blood purification can have an alignment which is not parallel to the axis X of the filter module  10 . The fibers  32  then run at the periphery at an angle to the longitudinal axis about the core module (ultrafilter) and thus have a larger effective length. The ideal design of an ultrafilter (a plurality of short fibers) would hereby be combined with that of a blood filter requiring diffusion (longer bundles). This oblique laying of the blood filter fibers can run in the opposite direction, similar to the technique of yarn bobbins. 
       FIG. 4  shows a modified second embodiment of a filter module  110 , with identical or comparable features being provided with identical reference numerals. The second embodiment substantially corresponds to the embodiment shown in  FIG. 1  with the exception of the following differences. 
     Alternatively, the blood can also be returned to the cap  50  on the inlet side by a suitable cap  60  through a central tube  90  which could also be arranged horizontally on the periphery of the housing  80 . The advantage of such a configuration is that all connections  52 ,  54 ,  62  and  82  are on one side of the module  110 . 
     The cap  50  having the feed for blood and dialysate receives an additional sealing ring  74  to separate the blood outlet from the dialysate space. 
       FIG. 5  shows a modified third embodiment of a filter module  210 , with identical or comparable features being provided with identical reference numerals. The third embodiment also substantially corresponds to the embodiment shown in  FIGS. 1 and 2  with the exception of the following differences. The blood inflow into the second filter stage  30  takes place via the passage  90  and via a deflection of blood flow B in the cap  60 . 
     The rotor of an (impeller) pump  220  can additionally be integrated in the cap  60  and the flow in the filter module  210  can be reversed as a possible modification, but one which is not necessary. To achieve the flow reversal, the opening slits  44  for the internal dialysate outlet are displaced in the direction of the dialysate inlet  54  and the internal dialysate outlet  83  is moved in the direction of the pump cap  60 . 
     To have all connections on one side, in this variant, the dialysate is returned in a passage  90 ′ on the periphery of the housing  80 . This channel  90 ′ opens into the connection cap  50  in the connection  82  or in the dialysate outlet  82 . 
     To facilitate the venting of the dialysate space, a small bore  84  can be provided just before the connection point to the end cap between the outwardly disposed dialysate passage  90 ′ and the inner dialysate space. The bore  84  has to be kept small to minimize the bypass current of dialysate resulting therefrom. 
       FIG. 6  shows a modified third embodiment of a filter module  310 , with identical or comparable features being provided with identical reference numerals. The general setup is identical to the embodiment shown in  FIG. 1 . 
     The core of the hollow fiber membrane bundle in this variant comprises 2 ultrafilters formed by the first filter stage  20  and the third filter stage  330  in that the innermost fibers  332  of the third filter stager  330  have in comparison to the fibers  22  surrounding them of the first filter stage  20  closed ends  336  on the one side and open ends  338  on the oppositely disposed side. The housing cap  60  on the blood outlet side has an additional chamber  65  in the central region through which the infusate can flow to the pump  320  and from there via the line  325  into the blood region  67 . This chamber  65  is separated from the blood region  67  by a seal  68 . 
     A part flow of the dialysate flows around the hollow fiber membranes  32  of the second filter stage  30  as in the embodiment shown in  FIG. 1  and is discharged again via the connector  82  located at the periphery. A second part flow of filtered dialysate is drawn at the center of the filter module  310  through the wall of the membranes  22  onto the lumen side of the third filter stage. An external pump (or a pump integrated in the cap similar to the pump  220  in accordance with the embodiment shown in  FIG. 5 ) establishes the required pressure difference. The pump  320  establishes the underpressure in the bundle  334 , that is in the third filter stage  330 , since these fibers  332  have open ends  338  on the outlet side. 
     The outlet diameter D 2  of this fiber bundle is smaller (cf.  FIGS. 7 and 8 ) than the core diameter of the molded bundle on the inlet side D 1 . It is thus ensured that dialysate is always filtered in two stages before it e.g. is infused as postdilution and/or predilution. The outlet diameter D 2  of the third filter stage  330  is thus designed smaller than the core diameter D 1  of the third filter stage  330  in the inlet region. It is thereby achieved that individual fibers which are unexpectedly obliquely disposed in the total bundle by the production do not project from the third filter stage  330  into the first filter stage  20 . A two-stage filtration is thereby advantageously ensured. 
     The invention being thus described, it will be apparent that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be recognized by one skilled in the art are intended to be included within the scope of the following claims.