CA1106774A - 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

7~L

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 construction hav-ing bundles of thousands of hollow fibers each a very narrow tubethat functions as a dialysis element, but this modified construc-tion still presents problems. An example of hollow apparatus is shown in U.S.P. 3,442,002 and a fiber has recently come into use for hollow fiber dialyzers in the deacetylated cellulose acetate fiber referred to in U.S.P. 3,545,209. These fibers are generally ~èquired 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 shipping and storing dialyzers based on such hollow fibers while the fibers are filled with water and with the water containing formaldehyde to keep it from develop-ing microbial growth. Before each use it then becomes necessary to flush out all the formaldehyde.
According to the present teachings, there is provided a tubular casing integrally molded to contain longitudinal parti-tioning that subdivides it into five longitudinally extending side-by-side passageways, three of the passagewavs being of much wider cross-section than the other two with the three wider passageways being about eaual in size. The partitioning contains inter-passage communication openings that permit fluid introduced into one of the wider passageways near one end of the casing to move through that passageway to a location near the other end of the casing, then move from there into one of the smaller passage-6~7~

ways and back through that smaller passageway to a location near the said one end, from there to move into a second of the wider passageways and through that passagewaY to a location near the other end from there into a smaller passageway and through that passageway back to a location near said one end and from there into the third wider passageway and through that passageway to a location near the other end. The casing is about 6 to about 12 inches long and the five passageways are clustered about a common longitudinal center line with the three wider passageways arranged in closely-packed triangular relationship with the two smaller passageways being each circular in cross-section.
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 inveht-ion;
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 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 embodirnent of the present invention.
The following exarnples illustrate very desirable manners of preparing hollow fiber dialyzers in accordance -4~ 6~

with the present application.

A dialysis casing such as shown at 10 in Fig. 1 and molded or cemented together from polycarbonate or polystyrsne resin, is first pro~ided. 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 9 16 being of enlarged bore having internal diameters about 1-7/8 lnches.
The tubular length of the interior of the casing is divided into three individual passageways 2~, 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 discharge tube 38 leads out from end 16.
~ leb 26 has flow control means at each end ~, 16 arranged so that fluid entering inlet 36 ~lows upwardly through passage-way 21 from end 14 to end 16, then at end 16 moves from the top of passageway 21 to the top of passageway 22, then downwardly through passageway 22 to lower end 14 where it then transfers to the bottom of passageway 23 along which it moves upwardly to end 16 for discharge through outlet 3a. To effect thi~
~low control, flange 31 is arranged as a barrier seal againstthe outer wall Or 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 flange 31 is cut out as shown at 40 to provide a ~low-through space 1~1 that thus opens bet~een the upper ends of passageways 21 a~ld 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 o~ casing end 14 to provide a flow-through 3~ ~pace 51 between the lower ends of passageways 22 and 23.

~5~

A batch of hollow cuprammonium regenerated cellulose fibers having a wall thickness of about 12 microns plu9 or minus 2 microns and an internal diameter of about 200 microns plus or minus 50 microns is unspooled, preferably from a plurality of spools in parallel strands 3 cut to a length of about 9 inches and carefully cleaned. As generall~ ~upplied these fibers are made by extruding cuprammonium cellulose solution through an annular die into R regenerating bath while introducing a water-immiscible liquid into the bore of the hollow extrudate. A typical water-insoluble li~uid is isopropylmyristate. After regeneration is completed careful washing with isopropanol removes such liquid. The interiors of the fibers can ~hen be wet with a softening agent such as glycerine, preferably leaving about 5% of the softening agent by weight of the clean fiber. This softening is not e~sen-tial but helps guard the fibers against breakage or damage during subsequent handling, and does not detract from the effectiveness by which the fibers are sealed into the casing 10 .
A bundle of two to three thousand fibers so prepared i3 then inserted into one of the passageways 21, 22, 23, 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 filled sleeve, narrow end first, into one of the passageways, and ~inally pulling the sleeve off the introduced bundle. At the narrow end of the taper the fibers are arranged to project ~rom the sleeve so they can be gripped to help pull the sleeve off the other ends of the fibers.
When all the passageways are filled with fibers, the '74 potting can be started. At each end of the casing eaoh bundleof fibers projects a short distance. Each of these pro~ecting ends i~ dlpped in melted carnauba wax whioh is then permitted to solidify after the oarnauba wax ha~ penetrated a very short distance into all of the indi~idual fibers. ~he casing is then clamped longitudinally between pottin~ 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 freshl~ mixed potting mixture i9 poured into the potting compound container This mixture can be a polyurethane prepolymer resin with a chain extender, or an epoxy cement mixture as described in Patent 3J442Joo2, or a hardenable polysiloxane liquid or other ~ettable resin.
When a hardenable polysiloxane liquid with a curing 15 agent such as chlorplatinic acid is used9 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 flo~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 i~ a cleanly cutting solid and a sharp metal blade is used to cut the potting mixture flush with the open ends 14, 16 of the casingO This leaves the construction as illu~trated in Fig. 1, the potting composition being shown at 56 and 57. Covers 61, 62 each equipped with a flow conneotion 64, 65 are then fitted to the ca~ing ends 14, 16 as by welding or cementing, although they can also be threaded in place i~ desired. The oonstruction is then oomplete and only needs a flushing through to romove the water-soluble softening agent from the inside of the hollow flbers before it is placed in service, The dialyzers can be stored either be~ore or a~ter washing out the softening agentJ without significantly a~ecting its dialysis properties.
When the dialyzer is used it is generally held with end 16 up, a source o~ dialyzate is conneoted to inlet 36, discharge 38 is connected to wastel and 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 ~orm in the dialyzate and tend to rise toward the upper end 16 of the dialyzer. To keep those bubbles ~rom becoming krapped at the upper snd3 of passageways 21 and 22 and collecting there in an amount that could interfere with the dialysis~ a small bleed 59 is sho~n as provided at the upper end of web flange 32. For a M ange with a wall thickness o~ 1/16 inch a round opening as little as 1/2 millimeter in diameter will enable the gas trapped at the above-mentloned ends to readily make its way into the upper end of passageway 23 and out through discharge opening 38, without 3ignificantly 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 ls related to the thickness o~ the wall through which it penetrates. For wall thicknesses greater than 1/16 inch the vent width is pre~erably a little larger than 1/2 millimeter.
A feature ol ths dialyzer construction o~ Fig. 1 is that such dialyzers are readily manufactured with more uni~orm dialysis e~fectiveness than corresponding dialyzers in which there is no partitioning and web 26 is completely omitted.
Notwithstanding the enlarged ends 14, 16 which ser~e a3 dialyzate mani~olds that bring the dialyzate into direct -~ 7t~

contact with the outer layers o~ fibers in the riber bundles~
the dialyzate has a tendency to make its way through one end of the dialyzer to the other through the easlest path and thus ~lnd and establish a ohannell even when the riberQ are fairly well packed in place. Such channeling greatly reduoes the ef~ectiveness o~ the d~alysis particularly through the walls o~ those fibers that are some distance laterally spaced from the channel. ~hen this happens with a dialyzer containing only a qingle dialyzate passagewayg itA efriciency bacomes so poor that it generally has to be discardedO
Such channeling i9 more likely to take place as the wall thickness of the hollow ~ibers diminishes and a9 the fiber diamster dacrease3; these cause the ~ibers to be more flexible so that lt is easier ror the dialyzate to create a channel by deflecting the ~ibers. l~all thicXnesses of about 5 to about 20 m~crons are suitable for e~ective use and thicknesses of ~rom about 10 to about 15 microns are preferred. Fibers with internal passageways not over about 500 microns wide~ prerer-ably ranging from about 100 to about 300 microns in width, are ~ery erfective. Cuprammonium regenerated hollow ~ibers o~ this type are relativel~ stirr, particularly when dry, and are accordingly very easy to handle in the assembling of a bundle for insertion in R dialyzer, and in the insertion itself.
In the construction o~ Fig. 1 a channeling-induced drop in e~ficienoy o~ passageway 21 can also occt~, but when that happens the dialyzat;e emerging ~rom passageway 21 is less loaded with contaminants so that it beoomes more e~eotive in its subsequent passage throt~h passageways 22 and 23.
In addition ~Lch o~ the pa~sageways 21, 22 and 23 i8 narrower than it would be without the web 26, and ohanneling , ''': . :

.-9~ 6i7~

become~ less likely in narrower passageways. Also the total length of ribers contacted by the dialyzate in the construction of Fig. 1 is three times the length contacted if web 26 were omitted, and the e~iciency loss through channeling diminishes as such length increases.
Because of the more reproducible graater efficiencies of the construction of Fig. 1, dialyzers having an operatin~
length between potting seals 56, 57, o~ only about 15 centi-meters can be readily manufaGtured with the desired high qualities. This small bulk is particularly desirable, desirable, although in general overall lengths of rrom about 6 to about 12 inches can be attractive for hospital u~e.

Figs. 5, 6, 7 and 8 illustrate a modified dialyzer 110 pursuant to the present invention. In this dialyzer there are three parallel dialyzer passageways along the lines of Fig. 1 but the flow of dialyzate is arranged so that throughout its ~iber-contacting path it moves on the outside o~ the individual fibers in a direction counterGurrent to the flow o~ blood or other medium being d-ialyzed within the fibers.
As in the construction of Fig. 1, dialyzer 110 has a central tubular section 112 with enlarged ends 114l 116 and wlth a partitionlng web 126 inserted or molded in section 112.
Web 126 has ~lange~ 131~ 132, 133 similar to the three flanges of web 26J and in addition also has two supplemental flange~
134, 135 that derine supplemental passageways 124, 125.
Tbe bundles of hollow ~ibers are contained in passage-ways 121, 122, 123; passageways 124, 125 being unfilled so that they provide paths ~or the dialyzate to ~low w~ile out ~9~

-10~ 79~

of contact with the fibers.
The flow of dialyzate is controlled by appropriate shaping o~ the web flanges in the construction of Fig. 5 so that it enters and ~lows up~ardly 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 tra~el through passage.iay 12~ and discharge at outlet 13~o For this result, the upper ends of webs 13~ 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 ~.
No gas vent is provided in the construction of Fig. 5 inasmuch as the dialyzate flow rate is fairly high in the very narro~ 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 a~ter a si~gle passage through the dialyzer and is not recirculated from outlet 130 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 be~ore it is introduced into the 25 dialyzer. This removes almost all of the dissolved gases, and the maintenance of qome pressure on the dialyzate 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 ~ 7~'~

triangular i~ desired, both in their external shape as well as in the shape of the passageways. ~imilarly, they do not have to be per~ectly linear in longitudinal direction.

Figs. 9 throu~h 13 illustrate a dialyzer 210 according to the present ~nvention which 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. ~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 o~ the mounted cover against that ridge.
Upon vibration in this manner the ridge and the ridge~engaging portion of the cover ~use as a result of the rrictional heating ef~ects of the vibration between them, and weld together making a very e~ective ~luid-tight seal.
The construction and operation o~ 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 ~or dialyzate return, and inter-passage spacings 241, are similarl~r numbered. However, to better seal the blood or other dialyzand away from undesired crevices and the like, covers 262 are each pro~ided 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 sur~ace o~ the cover and external sur~ace of the caslng wall.
To further help with such sealing, the potting seal 257 can be arranged to project out a short distance 267, such as ~!~ 7 1/8 inch, beyond the casing end.

Figs, 14, 15 and 16 illustrate a dlalyzer Ll12 having a generally rectangular confi~uration both in its external aspeot as well as in its passageways. Such a configuration makes better use of space and can contain more fibers than other con~igurations having the same overall dimensions.
The construction and operation of this exemplification~
as well as the numbering of its parts, i9 S imilar to that o~
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 of having the fiber-containing passageways 421, 422 and 423 arrayed generally circumferent~ly 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 o~ a sleeve, particularly if the walls of a casing end provide a gradual taper ~rom their large internal bore down to the smaller bore of oentral portion 12 or 112. Alternatively the bundles can be sleeved and the sleeves left in the dialyzer in position around the bundles. ;

~his alternative is particularly desirable when the sleeves are of relatively thin wall section, i4e. 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 -12_ 7~
readily sliding the b~ndles 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 ~.

f~ 7~

centimeters, as compared to an unpartitioned dialyzer~ reduces the number of' fibers per passagelay and thus simplifies the preparation of the individual bundlesO BJ way of illustration, the task of' preparing a 6000~f'iber bundle ~or an unpartitioned dialyzer is more complex than that of preparlng three 2000-~iber bundles for use in the dialyzer of' Fig. 1 or Fig~ 5 or Fig. 9.
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 o~
about 1/2 to 1 millimeter helps grip the fibers and keep them from being def'lected by the flow around them, thus reducing the tendency to channelling.
Another feature of the present invention i8 that the di~ferent compartments of the described dialyzers need nok be used for the same ~unction. One of the compartments can for example be used to hold an absorbent such as activated charcoal or the lil~e, instead of' f'ibers, so as to absorb impurities or other undesirable ingredients in the dialyzand. Diff'erent kinds of fibers can be used in different passageways to obtain dirferent dialysis effects on the dialyzand as it passes throu~h the dialyzer. Indeed some of the passageways, such as passageway 124, can be fllled with absorbent f'or the purpose of treating the dialyzate as it moves through the dialyzer and better condition the dialyzate for its passage through the remaining fiber-cont;aining passageways.
The potting of` the f'iber ends can be accomplished with techniques other than that described above. Thus the preliminary dip of the fibers to plug their bores can be into melted resin-modified wa~es or thermoplastic resins or ~.

7~7~L

compositions that harden to form thermosetting resins. The potting mixture itself can for example be used as a prel~mlnary dip of shallow depth9 followed by deeper potting- A1SOJ by maintaining slightly higher pressure in unplugged fiber bores as against the pressure over the potting mixture lnto 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 al~ernatively be sealed by melting the fiber ends when they are of fusible nature, and ln ~his 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 ~ay assures thorough sealing of the dial~zate chamber from the dialyzand gas pressure applied over the liquid potting composition during the potting, has a similar effeot~ One end of a ~iber bundle can accordingl~ 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 pottad 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 16~ 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 fact that a reverse osmosis process desalinating brackish water for instance, requires membranes of relati~el~ non-porous material such as .

polyvinyl chloride7 as well as the use of a driving pressure greater than the osmotic pressure and as high as practicableO
An attempt to carry out such a re~erse osmosis with the cupr-mmonium regenerated cellulose as dsscribed 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 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 whare 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 pre~erred to pass the fluid being treated around the hollow fibers so that the high pressures used on such fluids in reverse osmosis is appliad 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 in the oxygenation of blood where silicone fibers are preferred.
Obviously many modifications and variatlons of the present invention are possible in the light of the above teachings. It is, there~ore, to be understood that within the scope of the appended claims the invention may be practiced otherw~se than as specifically described.

Claims

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

l. A tubular casing integrally molded to contain longitudinal partitioning that subdivides it into five longitudinally extending side-by-side passageways, three of them being of much wider cross-section than the other two, the three wider passageways being about equal in size, the partitioning containing inter-passage communication openings that permit fluid introduced into one of the wider passageways near one end of the casing to move through that passageway to a location near the other end of the casing, then move from there into one of the smaller passageways and back through that smaller passageway to a location near said one end, from there move into a second wider passageway and through that passageway to a location near said other end, from there into the second smaller passageway and through that passageway back to a location near said one end, from there into the third wider passageway and through that passageway to a location near said other end, characterized in that the casing is about 6 to about 12 inches long, and in that the five passageways are clustered about a common longitudinal centerline with the three wider passageways arranged in closely-packed triangular relationship.
and the two smaller passageways are each circular in cross-section.