CA1106771A - Hollow fiber dialysis - Google Patents

Abstract

Abstract of the Disclosure Improved dialyzer construction has elongated tubular casing with enlarged casing ends-and longitudinally-extending partitioning that divides its interior into a plurality of generally parallel passageways containing hollow dialysis fibers, the casing ends containing di-alyzate flow manifolding and directing means for re-ceiving dialyzate from a supply thereof, directing it from one casing end to the other through one of the passageways around the fibers, and so to and fro through the successive passageways, finally directing the dialy-zate out through a discharge opening. The dialyzate flow can in each fiber-containing passageway be counter-current to the flow within the fibers of the liquid being dialyzed. A gas by-pass can be provided in the partitioning at one end to bleed out gas that tends to accumulate at the high point of the to-and-fro dialyzate travel.

Description

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The present invention relates to dialysis, particularly dialysis of liquids such as blood.
There have been many suggestions for improving dialysis equipment especially of the artificial kidney type. A great many so-called coil-type artificial kidneys are in use in which the dialysis element is a tube many inches in diameter, but flattened and spirally wound with a spacer to separate the turns of the winding. An artificial kidney so made is relatively large in size, and there have been suggestions for smaller constructions having bundles of thousands of hollow fibers each a very narrow tube that functions as a dialysis element, but this modified con-struction still presents problems. An example of hollow fiber apparatus is shown in U.S. P. 3,442,002, and a fiber which has recently come into use for hollow fiber dialyzers in the deacety-lated cellulose acetate fiber referred to in U.S. P. 3,545,209.
These fibers are generally required to be kept wet with water at all times after the de-acetylation, in order to maintain their dialytic permeability. This has led to the awkwardness of ship-ping and storing dialyzers based on such hollow fibers while the fibers are filled with water and with the water containing form-aldehyde to keep it from developing microbial growth. Before each use it then becomes necessary to flush out all the formaldehyde.
According to the present invention there is provided a hollow fiber dialyzer which has an elongated tubular casing con-taining partitioning which divides the interior into at least three separate longitudinally-extending passageways with dialy-zate flow directing means for receiving dialyzate from an external source and directing it to flow from one casing end to the other through one of the passageways and then back to the one casing end through another of the passageways and so to and fro length-wise through the other passageways and finally out of the casing.

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At least three of the passageways each have a longitudinally-extending bundle of elongated hollow blood dialysis fibers extend-ing lengthwise therethrough and means are provided connected to deliver blood to be dialyzed from an inlet to the fiber ends of each of the bundles at the same end of the casing and to receive the blood from the other ends of the hollow fibers for delivery to an outlet. The passageways which have the bundles of fibers are generally circular in cross-section throughout their length between the dialyzate entrance and exit ends and are clustered around a common centerline.
The invention will now be described in more detail, by way of example only r with reference to the accompanying drawings, in which:-Fig. 1 is an elevational view partly in section and partly broken away, of a hollow fiber dialyzer in accordance with the present invention;
Figs. 2, 3 and 4 are sectional views of the construction of Fig, 1, taken along the lines 2-2, 3-3 and 4-4, respectively;
Fig. 5 is a view similar to Fig. 1 of a modified hollow fiber dialyzer representative of the present invention;
Figs. 6, 7 and 8 are sectional views of the construction of Fi~g, 5 taken along the lines 6-6, 7-7 and 8-8 respectively;
Figs. 9, 10, 11 and 12 are views similar to Figs. 1, 2, 3 and 4 of a further modified dialyzer typical of the present invention;
Fi~g. 13 is a sectional view of a cap suitable for use with the construction oE Fig. 9; and Figs. 14, 15 and 16 are views similar to Figs. 1, 2 and 3 of yet another embodiment of the present invention.
The following examples illustrate very desirable manners of preparing hollow fiber dialyzers in accordance --3~
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with the present application.

A dialysis casing such as shown at 10 in Fig. 1 and molded or cemented together ~rom polycarbonate or polystyrene resin, is ~irst provided. This casing has an over-all length of about 7-1/2 inches with its lntermediate portion 12 having sn internal diameter of 1-3/8 inches, each end 14, 16 being Or enlarged bore having internal diameters about 1-7/8 inches.
The tubular length o~ the interior of the casing is divided into three lndividual passageways 21~ 22, 23 by an axial web 26 of three rlanges~ 31, 32 and 33. An inlet tube 36 opens into enlarged end 14, and a discharge tube 38 leads out from end 160 ~ .Veb 26 has ~low control means at each end ~ , 16 arranged so that ~luid entering lnlet 36 ~lows upwardly through passage-way 21 ~rom and 14 to end 16, then at end 16 moveq ~rom the top o~ passageway 21 to the top o~ passageway 22, then down~vardly through passageway 22 to lower end ~ where it then transfers to the bottom o~ passageway 23 along which it moves upwardly to end 16 for discharge through outlet 38. To ef~ect this flow control, flange 31 is arranged as a barrier seal againstthe outer wall of the casing throughout the length o~ lower end 14 as well as throughout the length of the intermediate portion 12, but not at the upper end 16. Instead at that upper end rlange 31 is cut out as shown at 40 to provide a ~low-through space 41 that thus opens between the upper ends Or passageways 21 and 22.
Flange 32 is similarly shaped in an opposite sense so that at its lower portion it provides an edge 50 spaced ~rom the lowest point of casing end 14 to provide a flow-through space 51 between the lower ends of passageways 22 and 23, A batch o~ hollow cuprammonium regenerated cellulose ~ibers having a wall thickness of about 12 microns plus or minus 2 microns and an internal diameter o~ about 200 microns plus or minus 50 microns is unspooled, pre~erably ~rom a plurality of spools in parallel strands~ cut to a length of about 9 inches and carefully cleaned. As generally supplied thess fibers are made by extruding cuprammonium cellulose solution through an annular die into a regenerating bath while introducing a water-immiscible liquid into the bore o~ the hollow extrudate. A typioal water-insoluble liquid is isopropylmyristate. After regeneration is completed care~ul ~ashing with isopropanol removes such liquid. The lnteriors of the fibers can then be wet with a softening agent such as glycerine, preferably leaving about 5% of the softening agent b~ weight o~ the clean ~iber. This softening is not e~sen-tial but helps guard the ~ibers against breakage or damage during subsequent handling, and does not detract from the effectiveness by which the ~ibers are sealed into the casing 10.
A bundle of two to three thousand ~ibers so prepared is then inserted into one o~ the passageways 21, 22, 23, and additional bundles in each of the remaining passageways. This insertion can be e~pedited by first sliding over the bundle a tapered sleeve of polyethylene, then introducing the ~illed sleeve, narro~,7 end first~ into one o~ the passageways, and ~inally pulling the sleeve o~ the introduced bundle. At the narrow end of t;he taper the ~ibers are arranged to project from the sleeve so they can be gripped to help pull the sleeve o~ the other ends o~ the fibers.

When all the passagelNays are ~illed wlth flbers, the -6 ~ 7~

potting can be ~tarted. At each end o~ the casing each bundle o~ ~ibers projects a short distance. Each of these pro~ecting ends i3 dlpped in melted carnauba wax which is then permitted to solidi~y after the carnauba wax has penetrated a very short distance into all o~ the individual fîbers. The casing is then clamped longitudinally between potting heads connected to a potting compound container as illustrated in Fig. 19 o~ Patent 3,442,oo2, and centrifuged as also indicated in that patent while the uncured liquid freghly mixed potting mixture i9 poured into the potting compound container. This mixture can be a polyurethane prepolymer resin with a chain extender, or an epo~y csment mixture as desoribed in Patent 3,442,oo2, or a hardenable polysiloxane liquid or other settable resin.
When a hardenable polysiloxane liquid with a curing 15 agent quch as chlorplatinic acid is used, the centri~uging iq conducted at about 350 g while the mixture is hea~ed~ and after about 1/2 hour at 150F. the potting mixture is cured to the point that it no longer ~lo~s. The potting heads are then unclamped and removed, and the curing completed by holding the dialyzer in an air oven at 150F for two hours. After that the potting mixture is a cleanly cutting solid and a sharp metal blade is used to cut the potting mixture ~lush with the open ends 14, 16 o~ the casing. This leaves the construction as illustrated in Fig. 1, the potting composition being shoun at 56 and 57, Covers 61, 62 each equipped with a ~low connection 64, 65 are then fitted to the casing ends 14, 16 as by welding or cementing, although they can also be threaded in place lf` desired. The construction is then oomplete and only needs a ~lushing through to remove the wator-soluble so~tenlng agent from the lnslde o~ the hollow ~1bers -7~ 67~

before it is placed in ~ervice, The dialyzers can be stored either before or after washing out the softening agent, without significantly affecting its dialysis properties.
l~hen the dialyzer is used it is generally held with end 5 16 up, a source of dialyzate is connected to inlet 36, discharge 38 is cor~ected to wa3te, and a supply of blood to be dialyzed connected to inlet 65 with a blood return to outlet 64i In use bubbles of air or other gases can form in the dialyzate and tend to rise toward the upper end 16 o~ the di~lyzer. To keep those bubbles from becoming trapped at the upper ends of passageways 21 and 22 and collecting there in an amount that could interfere with the dialysis, a small bleed 59 i3 shown as provided at the upper end of web flange 32, For a flange with a wall thickness of 1/16 inch a round opening as 15 little as 1/2 millimeter in diameter will enable the gas trapped at the abo~e-mentioned ends to readily make its way into the upper end of passageway 23 and out through dischar~e opening 38~ without significantly reducing the e~fectiveness of the dialysis. The gas vent can even be made slightly smaller as for example 0~3 mm~ in diameter. The optimum width of the vent is related to the thickness of the wall through which it penetrates. For wall thicknesses greater than 1/16 inch the vent width is preferably a little larger than 1/2 millimeter.
A feature o~ the dialyzer construction of Fig. 1 is that sush dialyzers are readily manufactured with more uniform dialysis effectiveness than corresponding dialyzers in which there is no partiti.oning and web 26 is completely omitted D
Notwithstanding the enlarged ends 14, 16 which serve as dialyzate manifolds that bring the dialyzate into direct --B~ 677 contact with the outer layers o~ ~lber~ in the ~ber bundles~
the dialyzate has a tendency to make its way through one end of the dialyzer to the other through the easiest path and thus ~lnd and establish a ¢hannel, e~en when the riberQ are ~airly well packed ~n place. Such channeling greQtly reduces the e~ectiveness of the dialysis particularly through the wall~
of those ~ibers that are some distance laterally spa~ad ~rom the channel. When this happens with Q dialyzer oontaining only a single dialyzate passageway~ its ef~iciency becomes so poor that it generally has to be di3carded.
Such channeling is more likely to take place as the wall thickness of the hollow fibers diminishes and as the riber diameter decreases; these oause the fibers to be more ~lexible so that it is easier ~or the dialyzate to create a channel by de~lecting the ribers. Wall thicknesses of about 5 to about 20 microns are suitable ~or effecti~e use and thicknesses o~ ~rom about 10 to about 15 microns are preferred, Fibers with internal passageway3 not over about 500 microns wide, prerer-ably ranging from about 100 to about 300 miorons ln width, are very e~ecti~e. Cuprammonium reganerated hollow ~ibers o~ this type are relatively stif~, particularly when dry~ and are accordingly very easy to handle in the assembling o~ a bundle for insertion in a dialyzer~ and in the insertion ~t3el~.
In the construction of Fig. 1 a channeling-induced drop in efficiency o~ passageway 21 can also occur, but when that happens the dialyzate emerging ~rom pa3sagewa~ 21 is le3s loaded with contaminailts so that it becomes more e~ective in its sub3equent passage through pa3sageways 22 and 23.
In addition each of the passageways 21, 22 and 23 is narrower than it would be without the web 26, and channeling ~9~

becomes less likely in narrower passa~eways. Also the total length of fibers contacted by the dialyzate in the construction of Fig. 1 is three times the length contacted ~ web 26 were omitted, and the efficiency loss through channeling diminishe3 as such length increases, Because of the more reproducible greater efficiencies Or the construction Or Figo 1~ dialyzers having an operating length between potting seals 56, 57, of only about 15 centi-meters can be readily manufactured with the desired high qualities. This small bulk is particularly desirable, desirable, although in general overall lengths of from about 6 to about 12 inches can be attractive for hospital useO

Figs. 5, 6, 7 and 8 illustrate a modified dialyzer 110 15 pursuant to the present invention~ In this dialyzer there are three parallel dialyzer passaæeways along the lines of Figo 1 but the flow of dialyzate is arranged so that throughout its fiber-contacting path it moves on the outside of the individual ribers in a direction countercurrent to the rlow of blood or other medium being d-ialyzed within the ~ibers.
As in the construction of Fig. 1, dialyzer 110 has a central tubular seotion 112 with enlarged ends 114, 115 and with a partitioning web 126 inserted or molded in section 112~

Web 126 has flanges 131, 132 ~ 133 similar to the three flanges o~ web 26, and in acldition also has two supplemental ~lange~
134, 135 that define supplemental passageways 12LI, 125.
The bundles oY hollow fibers are contained ln passage-ways 121, 122, 123; passageways 124, 125 being unfilled 90 that they provide paths for the dialyzate to flow while out ~1 O-of contact with the fibers.
The flo~ of dialyzate is controlled by appropriat0 shaping of the web flanges in the construction of Fig. 5 so that it enters and flows upwardly first through passage 121 then downwardly through passage 12~ then back upwardly through passageway 122 returning this time to the bottom via passageway 125, and finally completing the dialysis by an upward travel through passageway 123 and discharge at outlet 138. For this result, the upper ends of webs 134 and 135 are spaced from the inside wall of casing end 116 and the lo~Jer ends of webs 131 and 132 are spaced from the inside surface of casing end 114, as more clearly illustrated in Figs. 7 and ~.
No gas vent is provided in the construction o~ Fig. 5 inasmuch as the dialyzate flow rate is fairly high in the very narrow return passageways 124, 125. Thus a flow rate of only about one foot a second is generally sufficient to sweep out gas bubbles that tend to form. For slower flow rates, as for example when the dialyzate is discarded after a sl~gle passage through the dialyzer and i9 not recirculated from outlet 138 back to inlet 136, gas venting can be provided in the construc-tion of Fig. 5.
Gas venting can be eliminated where the dialyzate is treated to reduce gas evolution, as ~or example by boiling it under reduced pressure before it is introduced into the dialyzer. This removes almost all o~ the dissolved gases, and the maintenance o~ some pressure on the dialyzate as it i9 impelled through the dialyzer acts as an additional preventive to ga~ evolution.
The dialyzer casings of the present invention need not be circular in cross-section but can be oval, rectangular or triangular if desired, both in their external shape as well as in the shape of the passageways. Similarly, thay do not have to be parfectly linear in longitudinal direction.
EX~MPLE 3 Fi~s. 9 through 13 illustrate a dialyzer 210 according to the present invention ~vhich is gene~ally triangular in cross-section, particularly at its ends 214, 2160 Those ends each have a mounting rib 217 which helps in positioning end connector covers 262. Moreover each rib 217 can be provided with a ridge 219 which need onl~ be about 15 to about 20 mils high that helps in ~elding the cover in place as by sonic or ultrasonic vibration of the mounted cover against that ridge.
Upon vibration in this manner the ridge and the ridge-engaging portion of the cover fuse as a result of the ~rictional heating effects of the vibration between them, and weld together making a very effective fluid-tight seal.
The construction and operation of Figs. 9 through 13 generally corresponds to that of Figs~ 5 through 8, and similar portions such as partitioning web 226, passageways 221, 222 and 223 for receiving the hollow fibers, passageways 224 and 225 for dialyzate return, and inter-passage spacings 241, are similarly numbered. However, to better seal the blood or other dialyzand away from undesired crevices and the like, co~ers 262 are each provided with an internal sealing lip 26~ shaped to engage the potting seal 257 outside the fiber-containing zone.
The dialyzand is thus kept from penetrating into the crevice 265 between the internal surface o~ the cover and external surface o~ the casing wall.
To further help with such sealing, the potting seal 257 can be arranged to project out a short distanc0 267, such as , --12~ 67~

1/8 inch, beyond the casing end.

Figs. 14, 15 and 16 illustrate a dlalyzer 412 having a generally rectangular confi~;uration both in its external aspect 5 as well as in its passageuvays. Such a configuration makes better use of space and can contain more ~ibers than other configurations having the same overall dimensions.
The construction and operation of this exemplification, as well as the numbering of its parts, i~ similar to that of Figs. 1 through 4, except that its covers 462 and cover engagement are like those of Figs~ 9 through 13 without the internal sealing lip. Internal sealing is provided in ~ig~ 14 by having its end covers 462 tightly engage the outer margin of the potting seal. Also instead o~ having the ~iber-containing passageways 421, 422 and 423 arrayed generally circumferentiaL~y around casing 410, these passageways are arranged in a simple row all lying in what can be considered the same thick plane.
The fiber bundles can be inserted in the dialyzer passageways without the help of a sleeve, particularly if the 20 wallq of a casing end provide a gradual taper from their large internal bore down to the smaller bore of central portion 12 or 112. Alternatively the bundles can be sleeved and the sleeves left in ths dialyzer in position around the bundles.
This alternative is particularly desirable when the sleeves 25 ~re of relatively thin wall section3 i.e. about 3 mils, so that they do not occupy much room.
The insertion of the fiber bundles is also made easier if this is done when the casings are hot. The heat expands the casing and thus provides a little more room for more 7~
readily sliding the bundles into place, after which the casing cools down and tightly encloses the fibers, thus making for added efficiency. Instead of an elongated sleeve to help the fiber insertion, a single narrow length of plastic or even wire can be looped around a fiber bundle adjacent one end, and tied or crimped against the fibers so as to provide a tail for the bundle. The bundle can then be pulled through a passageway by first passing the tail through the passageway and then pull-ing on the tail.
It is generally desirable to clean the hollow fibers for the dialysis as by washing or rinsing them with a readily volatilizable solvent, particularly where the bores in the fibers contain a liquid which should not contact the dialyzand or dialyzate.
The advantages of partitioning are obtained when the dialyzer is partitioned to provide only two parallel dialyzing passageways. A very simple construction of this type has inlet and outlet tubes 36, 38 on opposite sides of the upper casing 16 with a single central web extending longitudinally the entire length of the casing but with an opening in its lower portion.
The partitioning can even be more subdivided than is shown in the drawings so as to provide 4 or 5 parallel dialysis passageways, but the use of more partitions takes away some of the space for fibers so that the bulk of the casing has to be increased to maintain the dialyzing effectiveness.
The partitioning of the present invention simplifies the mechanical handling in the manufacture of the dialyzer. The reduced width of the individual passageways, e.g. one to three .

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centimeters, as compared to an unpartitioned dialyzsr, reduces the number of fiber~ per passagaray and thus simpli~ies the preparation Or the individual bundles. By way o~ illustrationg the task Or preparing a 6000-fiber bun~le for an unpartitioned dialyzer is more complex than that of preparing three 2000-fiber bundles for use in the dialyzer of Fig. 1 or Fig~ ~ or Fig. 9.
The ~lber-containing passageways can also be double tapered as ~llustrated at 211 in Fig. 9 90 that they provide a constriction ~n their central portions. Such a constriction of about 1/2 to 1 millimeter helps grip the fibers and ~eep them from being deflected by the flow around them, thus reducing the tendency to channellin~
Another feature of the present invention is that the di~ferent compartments o~ the described dialyzers need not be used ~or the same function. One of the compartments can for example be used to hold an absorbent such RS activated charcoal or the li!~e, instead of fibers~ so as to absorb impurities or other undesirable ingredients in the dialyzand. Different kinds of fibers can be used in different passageways to obtain different dialysis effects on the dialyzand as it passes through the dialyzer. Indeed some of the passageways, such as passageway 124, can be ~illed with absorbent for the purpose of treating the dialyzate as it moves through the dialyzer and better condition the dialyzate ror its passage through the remaining fiber-containing passageways.
The potting Or the fiber ends can be accomplished with techniques other than that described above. Thus the preliminary dip o~ the ~ibers to plug their bores can be into melted resin-modi~ied waxes or thermoplastic resins or --15- ~ 7~

compositions that harden to rorm thermosetting resins. The potting mixture itself can ~or example be used as a preliminary dip of shallow depth9 ~ollowed by deeper potting. Also, by maintaining slightly higher pressure in unplugged fiber bores as against the pressure over the potting mixture into which the unplugged fiber ends are dipped, the potting mixture is kept at a low level within those bores and the preliminary dip to plug those bores can be completely eliminated. The bores can alternatively be sealed by melting the ~iber ends when they are of fusible nature, and in this way make a prior dip un-necessary.
'~hile centrifugal ~orce applied to the liquid potting mixture helps assure that such mixture thoroughly impregnates all crevices and pores around and between the ~ibers and in this way assures thorough sealing o~ the dialyzate chamber from the dialyzand gas pressure applied over the liquid potting composition during the potting, has a similar e~ect. One end o~ a ~iber bundle can accordingl~ be potted at a time, without the need for the centri~ugal pott~ng apparatus.
Also the covers 61, 62 can be arranged to snap on over the potted ends of the dialyzer, as shown in Fig. 5 at 161, 162 for example. Such covers can be relatively ~lexible and the potted ends they snap over can be fitted with ridges as at 16~ to help lock the snap-on covers in place.
The dialysis discussed above i9 to be distinguished ~rom osmosis in that the dialysis uses ~ibers whose walls are extremely porous, much too porous for use in osmosis. This comparison is more clearly shown by the ~act that a reverse osmosis process desAlinatlng brackish water for instance, requires membranes of relatively non-porous material such as ' ~ , -16~ 37~

polyvinyl chloride, as well as the use o~ a driving pressure greater than the osmotic pressure and as high as practicable.
An attempt to carry out such a reverse osmosis with the cupr-mmonium regenerated cellulose as described above, will merely cause the brackish water to rapidly filter through the regenerated cellulose fibers and emerge at the discharge face of the cellulose in substantially the same condition as it entered the entrance ~ace.
The dialyzer construction of the present invention can al~o be used with the dialyzate passing through the bores o~
the hollow ~lbers and the dialyzand moving along the outside of the fibers, although this arrangement is not desirable here blood is the dialyzand. However ~ith osmosis-type fibers, the structural arrangement of the present invention is suitable for osmotic processes such as reverse osmosis, and in such use it is pre~erred to pass the fluid being treated around the hollow ~ibers so that the high pressures used on such fluid3 in reverse osmosis is applied to the exteriors of the ~ibers. Fiber failures are then not likely to cause leakage.
The apparatus of the present invention is also suitable for use in gas separation, again with an appropriate type of fiber, or in gas treatment of liquids as in ~he oxygenation o~ blood where silicone fibers are preferred.
Obviously many modifications and variatlons of the present invention are possible in the light o~ the above teachings. It is, therefore, to be understood that within the scope of the appended claims the invention may be practiced other~ise than as specifically described.

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Claims (2)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1 . A hollow fiber dialyzer having an elongated tubular casing containing partitioning that divides its interior into at least three separate longitudinally-extending passageways, dialyzate flow directing means for receiving dialyzate from an external source and directing it to flow from one casing end to the other through one of the passageways and then back to said one casing end through another of the passageways and so to and fro lengthwise through the other passageways and finally out of the casing, at least three of the passageways each having a longitudinally-extending bundle of elongated hollow blood dialysis fibers extending lengthwise therethrough, and means connected to deliver blood to be dialyzed from an inlet to the fiber ends of each of said bundles at the same end of the casing and to receive the blood from the other ends of the hollow fibers for delivery to an outlet, characterized in that the passageways having said bundles of fibers are generally circular in cross-section throughout their length between the dialyzate entrance and exit ends and are clustered around a common centerline.

2 The hollow fiber dialyzer as in claim 1 wherein the remaining passageways do not contain dialysis fibers, and these latter passageways are located adjacent the lateral periphery of the elongated casing.