Hollow fiber dialysis

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 dialyzate flow manifolding and directing means for receiving 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 dialyzate 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.

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 
construction still presents problems. An example of hollow fiber apparatus 
is shown in U.S. Pat. No. 3,442, 002, and a fiber which has recently come 
into use for hollow fiber dialyzers is the deacetylated cellulose acetate 
fiber referred to in U.S. Pat. No. 3,546,209. 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 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 developing microbial growth. Before each use 
it then becomes necessary to flush out all the formaldehyde. 
Among the objects of the present invention is the provision of improved 
hollow fiber dialyzer constructions.

A feature of the present invention is the provision of a hollow fiber 
dialyzer having an elongated tubular casing with ends of larger bore than 
its central portion, the central portion containing 
longitudinally-extending partitioning that divides its interior into a 
plurality of generally parallel passageways, the casing ends containing 
dialyzate flow manifolding and directing means for receiving dialyzate 
from a supply thereof, directing it from one casing end to the other 
through one of the passageways, and so to and fro through the successive 
passageways, finally directing the dialyzate out through a discharge 
opening, bundles of parallel hollow dialysis fibers being crowded into at 
least all of the passageways in which the directing means directs 
dialyzate flow in the same direction. 
The following examples illustrate very desirable manners of preparing 
hollow fiber dialyzers in accordance with the present application. 
EXAMPLE 1 
A dialysis casing such as shown at 10 in FIG. 1 and molded or cemented 
together from polycarbonate or polystyrene resin, is first provided. This 
casing has an over-all length of about 71/2 inches with its intermediate 
portion 12 having an internal diameter of 13/8 inches, each end 14, 16 
being of enlarged bore having internal diameters about 11/2 inches. The 
tubular length of the interior of the casing is 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 discharge 
tube 38 leads out from end 16. 
Web 26 has flow control means at each end 14, 16 arranged so that fluid 
entering inlet 36 flows upwardly through passageway 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 38. To effect this flow 
control, flange 31 is arranged as a barrier seal against the outer wall of 
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 
flow-through space 41 that thus opens between the upper ends of 
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 from 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 of hollow cuprammonium regenerated cellulose fibers 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 from a plurality of spools in parallel strands, cut to a length 
of about 9 inches and carefully cleaned. As generally supplied these 
fibers are made be 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 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 such as glycerine, preferably 
leaving about 5% of the softening agent by weight of the clean fiber. This 
softening is not essential 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 is 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 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 off the other ends of the fibers. 
When all the passageways are filled with fibers, the potting can be 
started. At each end of the casing each bundle of fibers projects a short 
distance. Each of these projecting ends is dipped in melted carnauba wax 
which is then permitted to solidify after the carnauba wax has peenetrated 
a very short distance into all of the individual fibers. The casing is 
then clamped longitudinally between potting heads connected to a potting 
compound container as illustrated in FIG. 19 of U.S. Pat. No. 3,442,002, 
and centrifuged as also indicated in that patent while the uncured liquid 
freshly mixed potting mixture is 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 U.S. Pat. No. 
3,442,002, or a hardenable polysiloxane liquid or other settable resin. 
When a hardenable polysiloxane liquid with a curing agent such 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 150.degree. F. 
the potting mixture is cured to the point that it no longer flows. The 
potting heads are then unclamped and removed, and the curing completed by 
holding the dialyzer in an air oven at 150.degree. F. 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 flush with the open ends 14, 16 
of the casing. This leaves the construction as illustrated in FIG. 1, the 
potting composition being shown at 56 and 57. Covers 61, 62 each equipped 
with a flow connection 64, 65 are then fitted to the casing ends 14, 16 as 
by welding or cementing, although they can also be be threaded in place if 
desired. The construction is then complete and only needs a flushing 
through to remove the water-soluble softening agent from the inside of the 
hollow fibers before it is placed in service. The dialyzers can be stored 
either before or after washing out the softening agent, without 
significantly affecting its dialysis properties. 
When 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, 
and a supply of 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 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 is 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 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 effectiveness 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 of the dialyzer construction of FIG. 1 is that such dialyzers are 
readily manufactured with more uniform dialysis effectiveness than 
corresponding dialyzers in which there is no partitioning and web 26 is 
completely omitted. Notwithstanding the enlarged ends 14, 16 which serve 
as dialyzate manifolds that bring the dialyzate into direct contact with 
the outer layers of fibers in the fiber 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 find and establish a channel, even when 
the fibers are fairly well packed in place. Such channeling greatly 
reduces the effectiveness of the dialysis particularly through the walls 
of those fibers that are some distance laterally spaced from the channel. 
When this happens with a dialyzer containing only a single dialyzate 
passageway, its efficiency becomes so poor that it generally has to be 
discarded. 
Such channeling is more likely to take place as the wall thickness of the 
hollow fibers diminishes and as the fiber diameter decreases; these cause 
the fibers to be more flexible so that it is easier for the dialyzate to 
create a channel by deflecting the fibers. Wall thicknesses of about 5 to 
about 20 microns are suitable for effective use and thicknesses of from 
about 10 to about 15 microns are preferred. Fibers with internal 
passageways not over about 500 microns wide, preferably ranging from about 
100 to about 300 microns in width, are very effective. Cuprammonium 
regenerated hollow fibers of this type are relatively stiff, particularly 
when dry, and are accordingly very easy to handle in the assembling of a 
bundle for insertion in a dialyzer, and in the insertion itself. 
In the construction of FIG. 1 a channeling-induced drop in efficiency of 
passageway 21 can also occur, but when that happens the dialyzate emerging 
from passageway 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 becomes less likely in narrower 
passageways. Also the total length of fibers contacted by the dialyzate in 
the construction of FIG. 1 is three times the length contacted if web 26 
were omitted, and the efficiency loss through channeling diminishes as 
such length increases. 
Because of the more reproducible greater efficiencies of the construction 
of FIG. 1, dialyzers having an operating length between potting seals 56, 
57, of only about 15 centimeters can be readily manufactured with the 
desired high qualities. This small bulk is particularly desirable, 
although in general overall lengths of from about 6 to about 12 inches can 
be attractive for hospital use. 
EXAMPLE 2 
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 fiber-contacting path it moves on the 
outside of the individual fibers in a direction countercurrent to the flow 
of 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 of web 26, and in addition also has two 
supplemental flanges 134, 135 that define supplemental passageways 124, 
125. 
The bundles of hollow fibers are contained in passageways 121, 122, 123; 
passageways 124, 125 being unfilled so that they provide paths for the 
dialyzate to flow while out of contact with the fibers. 
The flow of dialyzate is controlled by appropriate 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 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 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 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 single 
passage through the dialyzer and is not recirculated from outlet 138 back 
to inlet 136, gas venting can be provided in the construction 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 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 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. 
EXAMPLE 3 
FIGS. 9 through 13 illustrate a dialyzer 210 according to the present 
invention 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. Moreover 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 fuse as a 
result of the frictional 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, 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 surface of the casing wall. 
To further help with such sealing, the potting seal 257 can be arranged to 
project out a short distance 267, such as 1/8 inch, beyond the casing end. 
EXAMPLE 4 
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 overall 
dimensions. 
The construction and operation of this exemplification, as well 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. Also 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 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 of 
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 when the sleeves 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 when 
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 pulling 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 centimeters, as compared to an 
unpartitioned dialyzer, reduces the number of fibers per passageway and 
thus simplifies the preparation of the individual bundles. By way of 
illustration, the task of preparing a 6000-fiber bundle 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. 5 or FIG. 9. 
The fiber-containing passageways can also be double tapered as illustrated 
at 211 in FIG. 9 so 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 is 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 like, 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 filled with 
absorbent for the purpose of treating the dialyzate as it moves through 
the dialyzer and better condition the dialyzate for its passage through 
the remaining fiber-containing passageways. 
The potting of the fiber 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 waxes or thermoplastic 
resins or compositions that harden to form thermosetting resins. The 
potting mixture itself can for example be used as a preliminary dip of 
shallow depth, followed 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 fiber ends when they are 
of fusible nature, and in this way make a prior dip unnecessary. 
While 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 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 fact that 
a reverse osmosis process desalinating brackish water for instance, 
requires membranes of relatively non-porous material such as polyvinyl 
chloride, as well as the use of a driving pressure greater than the 
osmotic pressure and as high as practicable. An attempt to carry out such 
a reverse osmosis with the cuprammonium 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 
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 where 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 hollow 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 in the oxygenation of blood where silicone fibers are 
preferred. 
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.