Background of the Invention

Capillary fiber dialyzers are currently being used in the dialysis of blood, and also show promise for use as oxygenators for blood and _^ for other types of semi- permeable diffusion apparatus. An example of such a capillary fiber dialyzer is the«CF® dialyzer sold by the Artificial Organs Division of Travenol Laboratories, Inc. Other forms of capillary dialyzers involving a multiple tube flow path include West German Patent No. 2,82 ,98 published on December 21,.1978; West German Patent No. 2,622,684, published November 24, 1977; Kohl U.S. Patent No. 3,557,962; and Riede U.S. Patent No. 4,016,082.

It has been long known to be desirable, particu¬ larly in blood dialysis as well as other diffusion tech- niques involving blood, for the blood flow paths to be of capillary nature, having a transverse dimension of, for example, 5-00 nicrons or less. These capillary flow paths for the blood or other material improve the dialysis efficiency of the device. Such capillary tubes are used, for example, in the commercial capillary fiber dialyzer mentioned above, as well as other commercial capillary fiber dialyzers.

It would be desirable to form joined arrays of capillary semipermeable tubes, for example, to obtain a sheet of such joined capillary tubes. However, no efficient and effective way of manufacturing joined arrays

of such tubes having a maximum transverse inner diameter o less than one millimeter has been available prior to this present invention.

In accordance with this invention, the diffusion ^' membrane unit defining an internal flow path is provided i which the individual flow channels through the diffusion membrane unit may preferably have a maximum transverse dimension of less than one millimeter or one thousand microns, with a minimum transverse dimension being as low as 70 or 100 microns, for greatly improved dialysis efficiency, or corresponding improvements in any other desired diffusion process.

Description of the ^Invention

In accordance with this invention, a method of making a unitary membrane made of the plastic, semipermeab material is provided in which the membrane defines a plura ity of parallel tubular passages passing longitudinally fr end to end of the membrane.

In accordance with this invention, plastic mater ial is extruded through an extrusion orifice exhibiting the cross-sectional shape of the membrane, while applying mandrel means through the orifice to displace the plastic material with the mandrel means in a manner corresponding to the pattern and shape of the parallel tubular passages. Thereafter, the Extruded plastic material is allowed to harden, and the hardened plastic material is separated from the mandrel means to open the tubular passages.

By this extrusion technique, a continuous proces membrane diffusion-.device may be formed out of an extruder and then cut into lengths and placed into a housing for us as a diffusion device such as a dialyzer, an oxygenator for blood, an ultrafiltration device, or a membrane plas a peresis device. For example, the blood can pass through

the membrane diffusion device, or a stack of such devices, in the tubular passages while dialysis solution or oxygen gas passes along the exteriors of such membrane diffusion devices. Alternatively, an opposite flow pattern can be utilized as well.

The plastic semipermeable material may be a form of cellulose, for example, Cupraphane-type cupraamonium cellulose, particularly in the instance where dialysis of blood is contemplated. Other plastic materials may be used to make up the unitary membrane diffusion device as may be desired.

While it is contemplated that thin, metallic wire mandrels may be used to define the tubular passages in the diffusion device of this invention, it is also contemplated to use as the mandrel means an organic liquid having a molecular weight in excess of 150, and substantially immiscible with the plastic material utilized to make the membrane diffusion device. For example, in the instance where a cellulose-type material is used, the organic liquid used for the mandrel device may be isopropyl myristate.

The technology for forming the liquid mandrel means out of an organic liquid is available to the prior art, and is presently used on a commercial basis- to manu¬ facture the capillary tubing made out of cellulose which constitutes the dialysis membrane in presently available hollow fiber-type dialysers, for example, the CF® dialyser sold by Travenol Laboratories, Inc. of Deerfield, Illinois. Preferably, the parallel tubular passages defined by the extrusion process of this invention have diameters of less than 1000 microns, and preferably no more than 500 microns, specifically 100 to 300 microns. The center to center spacing of the tubular passages is most preferably from 110 to 400 microns, so that they are separated by only thin walls, the minimum wall thickness between the tubular passages and the exterior being preferably as lew as 3 to 15 microns.

When the immiscible organic liquid is utilized as the mandrel, the resulting unitary membrane device is formed with the passages being filled with the organic liquid. It may be delivered to the user in this form, so that the user may drain the organic liquid or, alternativel the manufacturer can take the added step of removal of the organic liquid from the hardened plastic material to open the tubular passages.

Alternatively, the semipermeable membrane mater- ial may be any desired membrane material besides cellulose, for example,* polycarbonate resins, polyvinyl alcohol, or the like for dialysis procedures, for example he odialysis . If the diffusion membrane unit is used for the oxygenation of blood, polytetrafluoroethylene or silicone rubber may be used, by way of example. Also,_. conventional membrane materials for plasmapheresis or ultrafiltration may be used if desired.

Preferably, the unitary membrane diffusion device of this invention may have a minimum wall thickness between tubular passages and the exterior of 3 to 40 microns. Pre¬ ferably, the diameter of the tubular passages used in hemo¬ dialysis may be 20.0- - 50 microns. If the membrane diffu¬ sion device is intended for use for the oxygenation of bloo it may preferably have tubular passages of 500 - 200 micron in diameter.

As an advantage of this invention, the diffusion membrane unit ..of this invention may have thinner walls than the usually 'capillary membrane tubes found in fiber- type dialysers and the like, because the indivual tubular passageways are supported as a membrane unit and not just as separate fibers, which provides them a measure of protection.

In the drawings, Figure 1 is a perspective view of a stack of the membrane diffusion devices of this inven- tion, positioned within a housing for use as a diffusion device, for example a dialyser.

Figure 2 is a sectional view, taken on line 2-2 of Figure 1. _

_ρ.y.

Figure 3 is an enlarged elevational view of the face of extrusion apparatus shown in the process of ex¬ truding the unitary membrane diffusion device of this invention. Figure 4 is a longitudinal sectional view of the extrusion device of Figure 3 shown in the process of ex¬ truding the diffusion device of this invention, and further showing other process steps in the manufacture thereof, said drawing being in schematic form. Figure 5 is a transverse sectional view of another embodiment of the unitary membrane diffusion device of this invention.

Referring to Figures l.and 2, a stack of the membrane diffusion- devices of this invention is enclosed in a generally rectangular housing-having enlarged manifold ends. The individual unitary membrane diffusion devices 10, within housing 12, are preferably present in a number sufficient to provide enough diffusion surface area for a particular use desired. Diffusion _^ devices 10 may be sealed at their ends

14 in any conventional manner to define sealed manifold chambers 16, 18 at- the housing ends, respectively defining an inlet 19 and an outlet 21, which communicate only with tubular passages 23, while being sealed from the exterior of each diffusion device for the purpose of defining a first flow path through the device within tubular passages 23•

A second flow path through the diffusion device housing 12 along the exterior of diffusion devices 10 may then be defined between a second fluid inlet 20 and out¬ let 22, positioned in the sides of housing 12 in a manner which is analagous to conventional fiber dialyser tech¬ nology. The rectangular shape of housing 12 and diffusion devices 10 provides a substantially simplified and effi- cient diffusion device, which is easy to manufacture.

As shown in Figure 2, each of the diffusion

devices 10 define linear humps 26 on both sides of diffu¬ sion devices, and adjacent each tubular passage 23, so that the overall thickness of each unitary membrane device adjacent each parallel tubular passage 23 is increased over the thickness of the membrane device in the space between the tubular passages, for example at area 28. This provides flow channels 30 for the fluid that enters and exits through ports 20, 22 along membrane devices 10 on both sides thereof. The individual membrane devices 10 in the stack are retained in an orientation by housing 12 so that the facing humps 26 of each membrane device 10 abut each other to provide open channels 30 between the unitary membrane devices 10, for the flow of fluid in the second flow path, for example dialysis solution in the case of hemodialysiε.

Accordingly, blood, for example, can flow throug port 19, entering the open tubular passages 23 of each of the diffusion devices 10 in the stack enclosed within housing 12, while being sealed from flow along the exterio of each diffusion device 10. Thereafter, the blood flows into manifold 18 and out of port 21, as part of a conven¬ tional hemodialysi-s circuit, for example.

In this instance, dialysis solution can flow through inlet 20 into a manifold area 32 at one end of housing 12, flowing, for example, through transverse interior grooves 3* positioned on inner surfaces of both sides of housing _^ 12 to permit the distribution of dialysis solution along bo ^' tlϊ sides of the stack of diffusion de¬ vices. Apertures may be punched through areas 28 at one end of devices 10, to permit distribution of dialysis solution to all faces of the diffusion devices in the stack and to inter onnect flow channels 30.

The dialysis solution then runs along the variou channels 30 along the exteriors of members 10, passing optionally through additional punched aperture sections in areas 28 between the tubular passages 23 adjacent the

f O.V.Fi

other end of housing 12, so that the dialysis solution can be collected in transverse grooves 36 on the inner walls of housing 12, for flow communication with manifold 38 and dialysis solution outlet port 22. Accordingly, the diffusion device of this inven¬ tion can function as a very simple dialyser, utilizing segments of the extruded diffusion device 10 as the diffusion membrane.

Referring to Figure 3, the face of an extrusion device 3^ is shown, defining an extrusion orifice 36, through which the unitary membrane diffusion device of this invention may be extruded. As shown in Figure 4, a chamber 37 is filled with liquid- plastic material 38, for example a conventional cupraamonium "dope" solution con- taining alpha cellulose, copper"sulfate, and ammonia, the solution being pressurized by means of pump 40, which may continuously add cupraamonium solution to container 37. The pressurized cupraamonium solution is extruded through orifice into a bath of ^' caustic soda 43, which causes the prompt coagulation of the material.

Simultaneously with this extrusion process, which takes place through extrusion orifice 36, conduits 44 are provided, extending through tank 37, for the application of liquid isopropyl-myristate to serve as mandrel means and to define the open tubular passages 23 which, in this embodiment, are filled with the isopropyl myristate. The application of the column of isopropyl myristate can be balanced with the pressures in chamber 37 to form a solidi¬ fied membrane diffusion device containing the tubular passages 23, as shown in cross-section for ex ple in Figure 3.

Chamber 37 may be vertically positioned as shown in Figure 4. Alternatively, it may be horizontally posi¬ tioned, as shown in phantom, beneath the liquid level of the caustic soda bath 43, being sealed within an aperture within the wall of the container of the caustic soda bath.

OΛPI

Following the caustic treatment in container 42, a continuous length 46 of extruded cellulose membrane sheet may be carried by rollers 48, 0 and other rollers as desired into a wash bath and an acid bath in accordance with conventional technology for the preparation of coagu¬ lated cupraamonium cellulose materials. Thereafter, as shown schematically in Figure 4, the continuous strip of extruded material 46 can be severed by a knife member 2 or other means into discrete lengths 53, to form the unit- ary membrane diffusion devices, which may then be stacked and utilized in housing 12 as described above. Upon cutti the isopropyl myristate mandrel fluid, or other liquid as desired for the same purpose, ay be removed from open tubular passages 23, with the diffusion devices being pre- ferably washed in Freon or the like, dried, and then for¬ warded for assembly into diffusion devices as shown on Figure 1 ^' .

Referring to Figure 5, an alternative unitary membrane diffusion device 10a is shown., having flat outer faces 54 without the humps of the previous embodiment as shown in Figure 2. The open tubular passages 23a are pro¬ vided,* being made in a manner similar to that described above. In this particular embodiment, if stack of the diffusion devices 10a are used in a housing, it is de- sirable to separate them with a spacer member such as a porous screen or the like to facilitate the flow of fluid the outer faces 54 of the membrane diffusion device lba.

Alternatively, as a substitute for the liquid mandrel system shown in Figure 4, short metal mandrels of wire may be utilized. In this instance, Figure 3 shows the outer faces of those mandrels within open tubular passages 23, which maintain the form of the extruded structure for a period of time sufficient to permit coagulation of the extruded structure by the caustic solution, the length of the wire mandrels being governed by the time required for

coagulation to take place and the rate of advance of the extruded member.

The above has been offered for illustrative purposes only, and is not intended to limit the invention of this application, which is as disclosed in the claims below.

>ά ^χ - . ^'~ A υ