CA1106772A - 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 or the to-and-fro dialyzate travel.

Description

77~
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 flat-tened 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 fi`bers 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 formalde-hyde.
According to the present teachings, there is provided a hollow fiber dialyzer which has an elongated tubular casing con-taining partitioning that divides i-ts interior into at least five separate longitudinally-extending passageways with dialyzate flow directing means for receiving dialyzate from an external source and directing it to flow from one casing end to the other through 3Q one of the passageways and then back to the said one casing and through another of the passageways and so to and fro lengthwise through the other passageways and finally out of the casing with .~ ~ .

. ~ .

7;~

at least three of the passageways each having a longitudinally-extending bundle of elongated hollow blood dialysis fibers which extend lengthwise therethrough. Means are 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. At least two of the passageways which do not contain dialysis fibers and the three passageways which have the bundles of fibers are arranged~in closely-packed triangular relationship.
The invention will now be described in more detail, by way of example only, with reerence to the accompanying drawings, in which:-F~g. 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;
2Q Figs. 6, 7 and 8 are sectional views of the construction of Fig. 5 taken along the lines 6-6, 7-7 and 8-8, respectively;
F~gs. 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;
Fig. 13 is a sectional view of a cap suitable for use with the construction of 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 .~

with the present application.

A dialysis casing such as shown at 10 in Fig. 1 and molded or cemented together from polyc:arbonate or polystyrene resin, is ~irst provided. This casing has an over-all length o~ about 7-1/2 incheq with its intermediate portion 12 having an internal diameter of 1-3/8 inches, each end 14, 16 being o~ enlarged bore having internal diameters about 1~7/8 inches.
The tubular length of the interior of the casing i8 divided into three individual passageways 21, 22, 23 by an axial tveb 26 of three ~langes~ 31, 32 and 33. An inlet tube 36 opens into enlarged end 14, and a discharge tube 38 leads out from end 16~
l~'Jeb 26 has ~low control means at each end 14, 16 arranged ~o that ~luid entering inlet 36 flows upwardly through passage-way 21 from end 14 to end 16, then at end 16 moves ~rom the top of paqsageway 21 to the top of passageway 22, then downwardly through passageway 22 to lower end 14 where it then transrers 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 againQtthe outer wall o~ the casing throughout the length of 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 ~lange 31 is cut out as shown at 40 to provide a flow-through space l~l that thus opens between the upper ends o~ passageways 21 and 22.
Flanæe 32 is similarly shaped in an opposite sense so that at its lower portion it provides an edge 50 spaced ~rom the lowest point o~ casing end 14 to provide a flow-through space 51 between the lower ends of passageways 22 and 23.

. . .

~5~

A batch of hollow cuprammonium regenerated cellulose fiber3 having a wall thickness of about 12 microns plus or minus 2 microns and an internal diamet;er o~ about 200 microns plus or minus 50 microns is unspooled, preferably ~rom a plurality of spool3 in parallel strands, cut to a length of about g inches and carefully cleanedO As generally supplied these ribers are made by extruding cuprammonium cellulose solution through an annular die into a regenerating bath while introducing a water-immiscible liquid into the bore of the hollow extrudate. A typical water-insoluble liquid ls isopropylmyristate. After regeneration i9 completed care~ul washing with isopropanol removes such liquid. The interiors of the fibers can then be wet with a softening agent such as glycerine, preferably leaving about 5% of the softening agent by weight of the clean ~iber. This softening is not essen-tial but helps guard the fibers against breakage or damage during subsequent handling, and does not detract from the effectiveness by ~hich the fibers are sealed into the ca3ing 10.
A bundle of two to three thousand ~ibers so prepared is then inserted into one of the passage~ays 21, 22, 23, and additional bundles in each of the remaining pa~sa~eways. This insertion can be expedited by fir3t sliding over the bundle a tapered sleeve of polyethylene, then introducing the filled sleeve, narrow end first, into one of the passageways, and finally pulling the sleeve o~f the introduced bundle. At the narro~ end of the taper the ~ibers are arranged to project from the sleeve so they can be gripped to help pull the sleeve off the other ends of the fibers.

When all the passage~ays are ~illed with flbersJ the potting can be ~tarted. At each end of the casing each bundle o~ ~ibers pro~ects a short d~stance. Each o~ these proJecting ends is dipped in melted ¢arnauba wax which is then permitted to solidi~y after the carnauba vax has penetrated a very ~hort distance into all of the individual fibers. ~he casing is then clamped longitudinally between potting heads connected to a potting compound container as illustrated in Figo 19 o~ Patent 3,442,oo2, and centrifuged as also indicated in that patent while the uncured liquid freshly mixed potting mixture i3 poured into the potting compound container. This mixture csn be a polyurethane prepolymer resin with a chain extender, or an epoxy cement mixture as described ~n Patent 3,442,oo2, or a hardenable polysiloxane liquid or other settable resin.
When a hardenable poly3iloxane liquid wlth a curing agent ~uch as chlorplatinic acid is used~ the centrifuging is conducted at about 350 g while the mixture is heated, and after about 1/2 hour at 150F. the potting mixture is cured to the point that it no longer ~lows. The potting heads are then unclamped and remo~ed, and the curing completed b~ holding the dialyzer in an air oven at 150F for two hours. A~ter 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 shown

2~ Rt 56 and 57. Covers 61~ 62 each equipped with a flow connection 64, 6~ are then ~itted to the casing ends 14, 16 as by welding or cementingt although they can also be threaded in place i~ desired. The ¢onstruction is then complete and only needs a ~lushing through to remove the water-soluble so~tening agent ~rom the inside of the hollow f~bers ~7~ ~ 6 772 be~ore it is placed in service, The dialyzers can be stored either before or after washing out the softening agent9 without significantly affecting its dialysis properties.
IYhen the dialyzer is used it is generally held with end 16 up, a source of dialyzate is conneoted to inlet 36, discharge 38 is connected to waste, and a supply o~ blood to be dialyzed connected to inlet 65 with a blood return to outlet 64. In U39 bubbles of air or other gases can form in the dialyzate and tend to rise toward the upper end 16 o~ the dialyzer. To keep those bubbles from becoming trapped at the upper ends o~ passageways 21 and 22 and collecting there in an amount that could interfer~ with the dialysis~ a ~mall bleed 59 i3 shown as provided at the upper end of web ~lange 32. For a flange with a wall thiclmess o~ 1/16 inch a round opening as little as 1/2 millimeter in diameter will enable the gas trapped at the above-mentioned ends to readily make its way into the upper end of passageway 23 and out through discharge opening 38, without significantly reducing the erfectiveness of the dialysis. The gas vent can even be made sllghtly ~maller as for example 0.3 mm. in diameter. The optimum width of the vent is related to the thickness o~ the wall through which it penetrate~. For wall thiclmesses greater than 1/16 inGh the vent width is pre~erably a little larger than 1/2 millimeter.
A feature o~ the dialyzer construction o~ Fig. 1 is that such dialyzers are readily manufactured with more uni~orm dialysis effectiveness than corresponding dialyzers in which there is no partitioning and web 26 is oompletely omitted.
Notwithstanding the enlarged ends 14, 16 which serve as dialyzate manifolds that bring the dialyzate into direct -B ~ ~ 6 77 2 contact ~ith the outer layers o~ fibers in the ~iber bundles~
the dialyzate has a tenden¢y to make its way through one end of the dialyzer to the other through the easiest path and thu~
~ind and e~tablish a channel, even when the ~iber3 are fairly uell packed in place. Such channeling greatly reduces the e~ectiveness of the dialysis particularly through the walls of those ~ibers that are ome distance laterally spaced ~rom the channel. U~hen this happens with a dialyzer oontaining only a single dialy~ate passageway~ its efficiency becomes so poor that it generally has to be aiscQrded.
Such channeling i9 mors likely to take place as the wall thicknes~ of the hollow ~ibers diminishes and as the ~iber diameter decreases; these cause the ~ibers to be more ~lexible 90 that it i3 easier ~or the dialyzate to create a channel by deflecting the fibers. Wall thioknesses o~ about 5 to about 20 microns are suitable ~or e~ective use and thicknesses o~ ~rom about 10 to about 15 microns are pre~erred, Fibers with internal passageway3 not over about 500 micron~ wideJ pre~er-ably ranging ~rom about 100 to about 300 miorons in width, are very e~fective. Cuprammonium regenerated hollow ~ibers of thi~
type are relatively sti~f, partioularly when dry, and are aocordingly very easy to handle in the assembling o~ a bundle ~or insertlon in a dialyzer, and in the insertion it~el~.
In the con~truction o~ Fig. 1 R ohanneling-induced drop in e~ficisncy o~ pa~sageway 21 can also occur, but when that happens the dialyzate emerg~ng ~rom passageway 21 is less loaded with contaminants 90 that it becomes more ef~ective in its subsequent pass~ge through passageways 22 and 23.
In addition each of the passageways 21, 22 and 23 is nsrrower than it would be without the web 26~ and channeling _9~ 677~

becomes less likely in narrower pas~ageways. Also the total length of fibers contacted by the dialyzate in the construction of Fig. 1 is three times the length contaoted ~f web 26 were omitted, and the e~icienoy loss through channeling dimlnlshe3 as such length increases.
Because of the more reproducible greater e~iciencies o~ th~ construction of Fig. 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 desirable3 desirable, although in general overall lengths o~ ~rom about 6 to about 12 inches can be attractive for hospital US9 Figs. 5, 6, 7 and 8 illustrate a modified dialyzer 110 pursuant to the present inventionr In this dialyzer there are three parallel dialyzer passageways along the lines of Fig, 1 but the ~low of dialyzate is arranged so that throughout its ~iber-contacting path it moves on the outside o~ the individual fibers in a direction countercurrent to the ~low o~ blood or other medium being dialyzed within the fibers.
As in the construction of Fig. 1, dialyzer 110 has a central tubular section 112 with enlarged ends 114, 116 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 addition also has two supplemental flanges 134~ 135 that de~ine supplemental passageways 124, 125.
The bundles of hollow ~ibers are contained in passage-ways 121~ 122~ 123; passageways 124, 125 being un~illed so that they provide paths ~or the dialyzate to ~low whlle out -9~

~lo~ 7~7~

of contact with the fibers.
The flow of dialyzate is controlled by appropria~e shaping of the web flanges in the construction o~ Fig. 5 so that it enters and flows upwardly first through passage 121 then downwardly through passage 124 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 lower ends of webs 131 and 132 are spaced from the inside surface of casing end 114, as more clearly illustrated in Figs. 7 and 8.
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 o~ only about one foot a second is generally sufficient to sweep out gas bubbles that tend to form. For slower flow rates, as ~or example when the dialyzate is discarded after a single passage -through the dialyzer and is 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 for example by boiling it under reduced pressure before it is introduced into the dialyzer. This removes almost all of the dissolved gases, and the maintenance of some pressure Oll the dial~Tzate as it is impelled through the dialyzer acts as an additional preventive to gas evolution.
The dialyzer casings of the present invention need not be circular in cross-section but can be oval, rectangular or 6~2 triangular if desired, both in their external shape as well as in the shape of the passageways. Similarly, they do not have to be perfectly linear in longitudinal direction.

Figs. 9 through 13 illustrate a dialyzer 210 according to tne present invention ~hich is generally triangular in cross-section, particularly at its ends 214, 216. Those ends each have a mounting rib 217 which helps in positioning end connector covers 262. ~qoreover each rib 217 can be provided with a ridge 219 which need only be about 15 to about 20 mils high that helps in welding 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 ruse as a result of the frictional heating effects of the vibration between them, and weld together making a very ef~ective 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 ~or receiving the hollow fibers, passageways 224 and 225 ror di~alyzate 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, covers 262 are each provided with an internal sealing lip 263 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 of the cover and external sur~ace of the casing wall.
To further help with such sealing, the potting seal 257 ~0 can be arranged to project out a short distance 267, guch as ~12~ '6 1/8 inch, beyond the casing end.

EXAMPLE h Figs. 14, 15 and 16 illustrate a dialyzer 412 having A
generally rectangular configuration both in its external aspect as well as in its passageways Such a configuration makes better use of space and can contain more fibers than other configurations having the same averal:L dimensions.
The construction and operation of this exemplification, as well as the numbering of its parts, is similar to that of Figs. 1 through 49 except that its covers 462 and cover engagement are like those of Figs. 9 through 13 without the internal sealing lip. Internal seal~ng is provided in FigD 14 by having its end coverq 462 tightly engage the outer margin of the potting seal. Also instead of having the fiber-containing passageways 421, 422 and 423 arrayed generally circumforentially 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 walls of a casing end provide a gradual taper from their large internal bore down to the smaller bore o~ central portion 12 or 112. Alternatively the bundles can be sleeved and the sleeves left in the dialyzer in position around the bundles, This alternative is particularly desirable ~hen the sleeve~
are of relatively thin wall section, 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 wh0n the casings are hot. The heat expands the casing and thus provides a little more room for more .

... . .
' ' 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 partit:ioning 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 centimeters, as compared to an unpartitioned dialyzex, reduces the number of fibers per passager-ay and thus simpli~ies the preparation of the individual bundles~ By way of illustration~
the task of preparing a 6000-~iber bundle ~or an unpartitioned dialyzer is more complex than that Or preparing three 2000-fiber bundles for use in the dialyzer o~ Flg. 1 or Fig. ~ or Fig. g.
The fiber-containing passageways can also be double tapered as illustrated at 211 in Fig. 9 90 that they provide a constriction in their central portions. Such a constriction of about 1/2 to 1 millimeter helps grip the fibers and keep them from being deflected by the flow around them, thus reducing the tendency to channelling.
Another feature of the present invention i3 that the different compartments of the described dialyzers need not be used for the same function. One of the compartments can for example be used to hold an absorbent such as activated charcoal or the lil~e, instead of fibers~ so as to absorb impurities or other undesirable ingredients in the dialyzand. Different kinds of ~ibers can be used in different passageways to obtain di~ferent dialysis effects on the dialyzand as it passes through the dialyzer. Indeed some of the passageways, such as pa~sageway 124, can be filled with absorbent for the purpose of treating the dialyzate as it moves through the dialyzer and better condition the dialyæate for its passage through the remaining fiber-containing passageways.
The potting o* the fiber ends can be accomplished with techniques other than that described above. Thu3 the preliminary dip of the fibers to plug their bores can be into melted resin-modified wa~es or thermoplastic resins Or compositions that harden to form thermosetting resinsO The potting mixture itself can for example be used as a prel~mlnary dip of shallow depthl followed by deeper potting- A1SOJ by maintaining slightly higher pressure in unplugged fiber bores as against the pressure over the potting mixture into which the unplu~ged fiber ends are dipped9 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 altarnatively be sealed by melting the fiber ends when they are of fusible nature, and in this way make a prior dip un-nscessary.
'~hile centrifugal force applied to the liquid pottingmixture helps assure that such mixture thoroughly impregnates all crevices and pores around and between the fibers and in this way assures thorough sealing of the dialyzate chamber from the dialyzand gas pressure applied over the liquid potting composition during the potting, has a similar effect. One end of a fiber bundle oan accordingly be potted at a time, without the need for the centrifugal potting 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 flexible and the potted ends they snap over can be fitted with ridges as at 163 to help lock the snap-on covers in place.
The dialysis discussed above is to be distinguished from osmosis in that the dialysis uses fibers 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 desalinatin$ brackish water for instance, requires membranes of relativel~J non-porous material such as .

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 emer~e at the discharge face of the cellulose in substantially the same condition as it entered the entrance face.
The dialyzer construction of the present invention can also be used with the dialyzate passing through the bores of the hollow fibers and the dialyzand moving along the outside of the fibers, although this arrangement is not desirable here blood is the dialyzand. However with 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 preferred to pass the fluid being treated around the holloY/ fibers so that the high pressures used on such fluids in reverse osmosis is applied to the exteriors of the fibers. 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 ~n the oxygenation of blood where silicone fibers are pre~erred.
Obviously many modifications and variations of the present invention are possible in the light of the above teachings. It is, therefore~ to be understood that within the scope of the appended claims the invention may be practiced otherwise than as specifically described.

: : .

Claims (3)

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 five 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 there are at least two passageways which do not contain dialysis fibers, and the three passageways having said bundles of fibers are arranged in closely-packed triangular relationship.

2. The hollow fiber dialyzer as in claim 1 wherein the two passageways which do not contain dialysis fibers are smaller in cross-section that those passageways which contain dialysis fibers and are located adjacent the lateral periphery of the elongated casing, and the casing is molded of a transparent material.

3 . The hollow fiber dialyzer as in claim 1 wherein the two passageways which do not contain dialysis fibers are smaller in cross-section that those passageways which contain dialysis fibers and said two passageways of smaller cross-section are located adjacent the lateral pheriphery on the elongated casing, and the casing is molded of a resin selected from the group consisting of polystyrene and polycarbonate.