CA1106773A - 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

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 form-aldehyde.
~ ccording to the present teachings, there is provided a hollow fiber dialyzer which has an elongated tubular casing which contains partitioning that divides its interior into a plurality of separate longitudinally-extending passageways with di~alyzate flow directing means provided for receiving dialyzate from an external source and for directing it to flow from one end of the casing 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

-2-' passageways and finally out of the casing. At least two of the passageways have a longitudinally-extending bundle of elongated hollow blood dialysis fibers which extend lengthwise therethrough.
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 end of the hollow fibers for delivery to an outlet. At one end of the casing the flow directing means contains a gas by-pass connected between successive passageways to permit gas bubbles trapped at that end, when the dialyzer is operated with that end up, to be discharged out of the casing without having to be carried by the dialyzate to the other end.
The invention will now be described in more detail, by way of example only, with reference 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;
F~gs. 2, 3 and 4 are sectional views of the construction of 2n 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 Fig. 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;
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 followinq examples illustrate very desirable manners of preparing hollow fiber dialyzers in accordance ~' 67~3 uith the present application.

A dialysis casing such as shown at 10 in F~g. 1 and molded or cemented together from polycarbonate or polystyrene resin, is first provided. This casing has an over-all length of about 7-1/2 inches with its intermediate portion 12 having an internal diameter of 1-3/8 inches, each end 14, 16 being of enlarged bore having internal diameters about 1~7/6 inches.
The tubular length of the interior of the casing i8 divided into three individual passageways 21, 22, 23 by an axial web 26 of three flanges, 31, 32 and 33. An inlet tube 36 opens into enlarged end 14, and a dischargs tube 38 leads out from end 16.
Web 26 has flow control means at each end ~ , 16 arranged 90 that fluid entering inlet 36 flows upwardly through passage-way 21 from end 14 to end 16, then at end 16 moves ~rom the top o~ pa~sageway 21 to the top of passageway 22, then downwardly through passageway 22 to lower end 14 where it then transfers to the bottom o~ passageway 23 along which it moves upwardly to end 16 for discharge through outlet 38. To effect this flow control, flange 31 is arranged as a barrier seal againstthe outer wall of the caslng throughout the length of lower end 14 as well as throughout the length of the intermedia~e portion 12, but not at the upper end 16. Instead at that upper end flange 31 is cut out as shown at 40 to provid0 a ~low through space 41 that thus opens between the upper ends o~ passageways 21 and 22.
Flange 32 is similarly shaped in an opposite sense 80 that at its lower portion it provides an edge 50 spaced from the lowest point o~ casing end ll~ to provide a flow-through ~0 space 51 between the lower ends of passageways 22 and 23.

A batch of hollow cupram~onium regenerated cellulose ~iber3 having a wall thickness of about 12 microns plus or minus 2 microns and an internal diameter of about 200 microns plus or minus 50 microns is unspooled, preferably ~rom a plurality of spools in parallel strands, cut to a length of about 9 inches and carerully cleaned. As generally supplied these fibers are made by egtruding cu;prammonium cellulo~e solution through an annular die into a regenerating bath wh~le introducing a water-immiscible liquid into the bore of the hollow extrudate. A typical water-insoluble liquid is isopropylmyristate. After regeneration is completed careful washing with isopropanol removes such liquid. The interiors of the fibers can then be wet with a softening agent 3uch as glycerine, preferably leaving about 5~ of the softening agent by weight of the clean fiber. 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 casing 10.
A bundle of two to three thousand ~ibers so prepared is then inserted into one of the passageways 21, 22, 23J and additional bundles in each of the remaining passageways. This insertion can be expedited by first sliding over the bundle a tapered sleeve of polyethylene, then introducing the ~illed sleeve, narrow end first, into one o~ the passageways, and finally pulling the sleeve off the introduced bundle. At the narrow end of the taper the fibers are arranged to project from the sleeve so they can be gripped to help pull the sleeve of~ the other ends of the fibers.

IVhen all the passageways are filled with fibers, the -6 ~ 73 potting ean be started. At each end o~ the casing each bundle o~ fibers pro~eots a short distance. ~Each o~ these pro~ecting ends i9 dlpped in melted oarnauba wax ~which is then permitted to solidi~y after the carnauba wax has penstrated a very short distanca into all o~ the individual f'ibers. ~he casing is than clamped longitudinallg between potting heads connected to a potting compound container as illustrated in Fig. 19 of' Patent

3,442,oo2, and centrifuged as also indicated in that patent while the uncured liquid freshly 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 cement mixture as described in Patent 3,442,oo2, or a hardenable polysiloxane liquid or other settable resin.
When a hardenable poly~iloxane liquid with a curing agent such as chlorplatinic acid is used, the centrif'uging is conducted at about 350 g while the mixture is hea~ed~ and a~ter about 1/2 hour at 150F. the potting mixture is cured to the point that it no longer f'lows. The potting heads are then unclamped and removed, and the curing completed by holding the dialyzer in an air oven at 150F f`or two hours. A~ter that the potting mixture is a cleanly cutting solid and a sharp metal blade i3 used to cut the potting mixture f'lush with the open ends 14, 16 o~ the casing. This leaves the construction as illustrated in Fig. 1, the potting composition being sho~n at 56 and 57. Covers 61, 62 each equipped with a f`low connection 64, 65 are then fitted to the casing ends 14, 16 as by ~elding or cementing~ although they can also be threaded in placs lf' desired. The construction ls then oomplete and only needs a flushing through to remove the water-soluble sof'tening aKent ~rom the inside of the hollow fibers ~6-7~ i7~3 be~ore it is placed in service. The dialyzers can be stored either be~ore or a~ter washing out the softening agent, without significantly a~fecting its dialysis properties.
l~hen the dialyzer is used it is generally held with end 16 up, a source of dialyzate is connected to inlet 36, discharge 38 is connected to waste, arld a supply o~ blood to be dialyzed connected to inlet 65 with a blood return to outlet 64. In use bubbles of air or other gases can form in the dialyzate and tend to rise toward the upper end 16 of the dialyzer. To keep those bubbles ~rom becoming trapped at the upper ends o~ passageways 21 and 22 and collecting there in an amount that could interfere uith the dialysis~ a small bleed 59 i3 shown as provlded at the upper end of web ~lange 32, For a flange with a wall thickness o~ 1/16 inch a round opening as little as 1/2 millimeter in diam3ter will enable the gas trapped at the above-mentioned ends to readily make its way into the upper end o~ passageway 23 and out through discharge opening 38, without signi~icantly reducing the er~ectiveness o~ the dialysis. The gas vent can even be m~de slightly smaller as ~or example 0.3 mm. in diameter. The optimum width o~ the vent is related to the thickness o~ 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 ~eature Or the dialyzer construction o~ Fig. 1 is that such dialyzers are readily manu~actured with more uni~orm dialysis ef~ectiYeness than corresponding dialyzers in which there is no partitioning and web 26 is completely omitted.
Notuithstanding the enlarged ends 14, 16 which serve as dialyzate mani~olds that bring the dialyzate into direct ~ 7 contact with the outer layers o~ ~iber3 in the ~lber bundles~
the dialyzate has a tendenc~ to make iLts way throu~h one end of the dialyzer to the other through the e~sie~t path and thus ~ind and e~tablish a channel, even when the flbers are ~airly well packed in place. Such channeli~g greatly reduces the e~fectiveness Or the dialysis particularly through the walls o~ those fibers that are some distance laterally spaced ~rom the channel. When this happens with Q dialyzer oontaining only a single dialyzate passageway~ lt3 ef~iciency becomes so poor that it generally has to be discarded.
Such channeling i9 mors likely to ta~e place as the wall thickness of the hollow fiber~ diminishes and as the fiber diameter decreases; these cause the fibers to be mors flexible 90 that lt is easier for the dialyzate to create a channel by de~lecting the fibers. l~all thicknesses of about 5 to about 20 microns are suitable for e~ective use and thioknesses of ~rom about 10 to about 15 microns are pre~erred. Fibers with internal passageways not over about 500 m~crons wide, prerer-ably ranging ~rom about 100 to about 300 m~crons in widthg are very effective. Cuprammonium regenerated hollow ~ibers of this type are relatively sti~f, particularly when dry~ and are accordingly very ea~y to handle in the assembling of a bundle ~or insertion in a dialyzer, and in the insertion it~el~.
In the con3truction o~ Fig. 1 a channeling-induced drop in erficiency of passageway 21 can also occur, but when that happens the dialyzate emerging from pa~sageway 21 is less loaded with contaminants so that it becomes more effective in its subsequent passage through passageways 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~ 3 bscome~ less likely in narrower passageways. Also the total length of ~ibers contacted by the dialyzate in the construction o~ ~ig. 1 is three times the length oontacted ~ web 26 were omitted, and the e~ficiency loss through channeling diminishes as such length increases.
Because of the more reproducible greater e~iciencies of the construction o~ Fig~ 1, dialyzers having an operating length between potting seals 56, 57, of only about 15 centi-meters can be readily man~actured with the desired high qualities. This small bulk is particularly desirable, desirable, although in general overall lengths of ~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 invention. In this dialyzer there arethree parallel dialyzer passageways along the lines o~ Fig, 1 but the ~low o~ dialyzate is arranged so that throughout its fiber-contacting path it mo~es on the outside o~ the individual fibers in a direction countercurrent to the ~low o~ blood or other medium being d-ialyzed within the ~ibers.
As in the construction o~ Fig~ lg dialyzer 110 has a central tubular section 112 with enlarged ends 1141 116 and with a partitioning web 126 inserted or molded in section 112.
Web 126 has ~langss 131, 132, 133 similar to the three flanges ~ web 26, and in a~ldition also has two supplemental ~langes 134, 135 that de~ine supplemental passageways 12ll, 125.
~ he bundle~ o~ hollow ~ibers are contained in passage-ways 121, 122, 123; passageways 124, 125 being unfilled so that they provide paths ~or the dialyzate to flow while out ~9_ ~10~ '773 of contact with the fibers.
The flow of dialyzate is controlled by approprlate 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 passage~iay 122 returning this tlme to the bottom via passageway 125, and ~inally completing the dialysis by an upward travel through passageway 123 and discharge at outlet 138. For this result, the upper ends o~ webs 13~ and ~35 are spaced ~rom the inside wall of casing end 116 and the lower ends o~ webs 131 and 132 are spaced ~rom the inside surface of casing end 114, as more clearly illustrated in Figs. 7 and ~. -No gas vent is provided in the construction of 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 i9 generally su~icient to sweep out gas bubbles that tend to form. For slower flow rates, as ror example when the dialyzate is discarded after a si~gle passage through the dialyzer and is not recirculated ~rom outlet 138 20 back to inlet 136, gas venting can be provided in the construc- -tion of Fig. 5 .
Gas venting can be eliminated ~here 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 on the dialyzate as it i9 lmpelled 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 o~al, rectangular or triangular i~ desired, both in their external shape as well as in the shape o~ the passageways. Similarly, they do not have to be per~ectly linear in longitudinal direction.

Figs. 9 through 13 illustrate a dialyzer 210 according to the present invention which ls generally triangular in cross-section, particularly at its ends 214~ 2165 Those ends each have a mounting rib 217 which helps in positioning end connector covers 262. ~oreover 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 o~ the cover ruse as a result Or the frictional heating e~ects o~ the vibration between them, and weld together making a very e~ective M uid-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 ~ibers, 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 ~rom undesired crevices and the like, covers 262 are each provided with an internal sealing lip 263 shap~d to engage the potting seal 257 outside the ~iber-containing zone.
The dialyzand is thus kept ~rom penetrating into the crevice 265 between the internal sur~ace of the cover and external sur~ace o~ the casing wall.
To ~urther help with such sealing, the potting seal 257 can be arranged to project out a short distance 267, such as .

~677;3 1/8 inch, beyond the casing end.

Figs. 14, 15 and 16 illustrate a dialyzer Ll12 having a gen_rally rectangular configuration both in its external aspect as well as in its passageways. Such a configuration makes better use ol space and can contain more fibers than other com~igurations having the same overall dimensions.
The construction and operation of this exempli~ication, as ~Jell as the numbering of its parts, is 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 Fig~ 14 by having its end covers 462 tightly engage the outer margin of the potting seal. Al30 instead of having the fiber-containing passageways 421, 422 and 423 arrayed generally circumferentially 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 dial-yzer passageways without the help of a sleeve, particularly i~ the walls of a casing end provide a gradual taper ~rom their large internal bore down to the smaller bore of central portion 12 or 112. Alternatively the bundles can be sleeved and the sleeves le~t in tht~ dialyzer in position around the bundles.
This alternative i9 particularly desirable when the sleeves are o~ relatively thin wall section, i.e. about 3 mils, so that they do not occupy much room.
The insertion of the ~iber 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 - . .

j773 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 ~ores 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 , ~

centimeters, as compared to an unpartitioned dialyzer, reduces the number of fibers per passageway and thus simpli~ies the preparation of the individual bundles. By way o~ illustration, the task o~ preparing a 6000 fibsr bundle ~or an unpartitioned dialyzer is more complex than that o~ preparing three 2000-~iber bundles for use in the dialyzer of Fig. 1 or Figo 5 or Fig~ 9.
The ~lber~containing passageways can also be double tapered as illustrated at 211 in Fig. 9 30 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 ~rom being de~lected by the ~low around them, thus reducing the tendency to channelling.
Another ~eature o~ the present invention is that the di~erent compartments o~ the described dialyzers need not be used ~or the same function. One of the compartments can ~or 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. Di~ferent kinds o~ fibers can be used in di~ferent passageways to obtain different dialysis e~fects on the dialyzand as it passes through the dialyzer. Indeed some o~ the passageways, such as passageway 124, can be ~illed with absorbent ~or the purpose o~ treating the dialyzate as it moves through the dialyzer and better condition the dialyzate ~or 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 ~ .

'7 compositions that harden to form thermosetting resins. The potting mixture itself can for example be used as a prel~Dinary dip of shallow depth~ follo~ed by deeper potting. Also, by maintaining slightly higher pressure in unplug~ed 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 eliminatedv The bores can alternatively be sealed by melting the fiber ends when they are of fusible nature, and in this way make a prior dip un-necessary.
'~hile centrifugal force applied to the liquid potting mixture 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 can accordingly be potted at a time9 without the need ~or 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 relatîvely 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. ~his comparison is more clearly shown by the fact that a reverse osmosis process desalinating brackish water for instance, requires membranes of relatively non-porous material such as -16~ 77 ~

polyvinyl chloride, as well as the use of a driving pressure graater than the osmotic pressure and as high as praoticable.
An attempt to oarry out suoh a reverse osmosis with the oupr-mmonium regenerated oellulose as described above, will merely cause the brackish water to rapidly filter through the regenerated cellulose fibers and emerge at the disoharge 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 dialy7ate passing through the bores of the hollow flbers and the dialyzand moving along the outside of the fibers, although this arrangement is not desirable where blood is the dialyzand. However with osmosiswtype fibers, the structural arrangement o~ the present invention is 5 suitable for osmotic processes such as reverse osmosis3 and in such use it is pre~erred to pass the fluid being treated around the hollo~t fibers so that the high pressures used on such fluids in reverse osmosis is applied to the exteriors of the f~bers. ~iber 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 the oxygenation of blood where silicone fibers are preferred.
Obviously man~ modifications and variations of the 25 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

}he 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 a plurality of separate longitudially-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 passage-ways and so to and fro lengthwise through the other passageways and finally out of the casing, at least two 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 at one end of the casing the flow directing means contains a gas by-pass connected between successive passageways to permit gas bubbles trapped at that end, when the dialyzer is operated with that end up, to be discharged out of the casing without having to be carried by the dialyzate to the other end.