Note: Descriptions are shown in the official language in which they were submitted.
1100~8~
The present invention relates to dialysis, particularly
dialysis of liquids such as blood.
There have been many suggestions for improving dialysis equip-
ment especially of the artificial kidney type. A great many so-
called coil-type artificial kidneys are in use in which the dialy-
sis 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.
Patent 3,442,002, and a fiber which has recently come into use for
hollow fiber dialyzers in the deacetylated cellulose acetate fiber
referred to in U.S. Patent 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 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.
Thus, in accordance with the present teachings, a hollow
fiber dialyzer is provided which has an elongated tubular casing
which contains partitioning that divides its interior into a
plurality of 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 one of the passageways and then back to the one
casing end through another of the passageways and so to and fro
lengthwise through the other passageways and finally out of the
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casing, at least two of the passageways each having a longitudin-
ally-extending bundle of elongated hollow blood dialysis fibers
extending lengthwise therethrough with means connected to deliver
blood to be dialyzed from an inlet to the fiber end 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.
The dialyzer is characterized in that only some but not all of the
passageways have bundles of fibers and the remaining passageways
do not contain dialysis fibers, and the dialyzate flow directing
means directs dialyzate to flow from one casing end to the other
in alternating fashion through the passageways having bundles of
fibers and the passageways which do not contain fibers so that the
dialyzate flow through each of the passageways having bundles of
fibers is always in the same lengthwise direction.
The invention will now be described in more detail, by way of
example only, with reference to the accompanying drawings, in which:
Fig. 1 is an elevational view partly in section and partly
broken away, of a hollow fiber dialyzer in accordance with the
present invention;
Figs. 2, 3 and 4 are sectional views of the construction of
Fig. 1, taken along the lines 2-2, 3-3 and 4-4, respectively;
Fig. 5 is a view similar to Fig. 1 of a modified hollow dial-
yzer 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 moldified 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 manner of pre-
paring hollow fiber dialyzers in accordance
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with th~ present application.
EXAMPLE 1
: A dialysi~ 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
Or about 7-1/2 inches with its intermediate portion 12 having
an internal diameter of 1-3/~ inches, each end 14, 16 being
of enlarged bore having internal diameters about 1-7/8 inches.
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.
Web 26 has ~low oontrol means at each end 14, 16 arranged
90 that fluid entering inlet 36 ~low~ upwardly through passaee-
way 21 ~rom end 14 to end 16, then at end 16 moves rrom the top
of passageway 21 to the top o~ passageway 22, then downwardly
through passageway 22 to lower end 14 where it then transfers
to the bottom Or passageway 23 along which it moves upwardly
to end 16 for discharge through outlet 38. ~o efrect this
flow control, flange 31 is arranged as a barrier seal againstthe outer wall o~ the oasing throughout the length of lower
end 14 as w911 as throughout the length of the intermediate
portion 12~ but not at the upper end 16. Instead at that
upper end Mange 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 simllarly shaped in an opposite sense so
that at its lower portion it provides an edge 50 spaced rrom
the lowest point o~ casing end 14 to provide a ~low-through
space 51 between the lower ends of passageways 22 and 23.
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A batch of hollow cuprammonium regenerated celluloqe
~ibers 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, pre~erably from a
plurality of spools in parallel strands, cut to a length of
about 9 inches and carefully cleaned. As generally supplied
these ~ibers are made by extruding cuprammonium cellulose
solution through an annular die into a regenerating bath while
introducing a water-immi~cible liquid into the bore of the
hollow extrudate. A typical water-insoluble liquid is
isopropylmyristate. After regeneration is completed carerul
washing with isopropanol removes such liquid. The interiors
o~ the ribers can then be wet with a sortening agent such as
glycerinef preferably leaving about 5% o~ the ~oftening agent
15 by weight Or the clean riber. Thi9 sortening is not essen-
tial but helps guard the ribers against breakage or damage
during subsequent handling, and does not detract rrom the
erreotiveness by which the ribers are sealed into the casing
10.
A bundle o~ two to three thousand ribers so prepared i9
then inserted into one Or the passageways 21, 22, 23, and
additional bundles in each o~ the remaining passageways. This
insertion can be expedited by ~irst sliding over the bundle a
tapered sleeve of polyethylene, then introducing the filled
25 sleeve, narrow end first, into one of the passageway~, and
finally pulling the sleeve o~f the introduced bundle. At
the narrow end of the taper the ~ibers are arranged to
project from the sleeve so they can be gripped to help pull
the sleeve of~ the other ends Or the fibers.
When all the passageways are rilled with ~ibers, the
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potting can be started. At each end of the casing each bundleo~ fibers projects Q short distance. Each of these pro~ecting
ends is dipped in melted carnauba wax which is then permitted
to solidi~ after the carnauba wax has penetrated a very short
distance into all of the individual fibers. Thc casing is then
clamped longitudinally between potting heads connected to a
pottlng ¢ompound container as illustrated in Fig. 19 of Patent
3,442~oo2, and centrifuged as also indicated in that patent
~hile 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 Patent 3,442,002, or
a hardenable polysiloxane liquid or other settable resin.
When a hardenable polysiloxane liquid with a ~uring
agent such as chlorplatinic aoid i9 u~ed, the ¢entrifuging is
oonduoted at about 350 g while the mixture ls 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
unolamped and removed, and the curing completed by holding the
dialyzer in an air oven at 150F for two hours. After that
the potting mixture is a cleanly cutting solid ~nd 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 ~low
conneetion 64, 65 are then ~itted to the ca9ing ends 14, 16
as by welding or cementing~ although they can also be
threaded in place if desired. The ¢onstruction ls then
complete and only needs a ~lushing through to remove the water-
soluble softening agent ~rom the inside of the hollow flbers
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before it i~ placed in ~ervice, The dialyzers can be stored
either before or after washing out the sortening agent, without
significantly a~fecting its dialysis properties,
When the dialyzer is used it is generally held with end
16 up, a ~ouroe of dialyzate is connected to inlet 36,
discharge 38 i8 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 ~orm in the
dialyzate and tend to rise toward the upper end 16 o~ the
dialyzer. ~o keep those bubbles from becoming trapped at the
upper ends o~ passageways 21 and 22 and collecting there in an
amount that could inter~ere with the dialysis~ a small hleed
59 is shown as provided at the upper end of web flange 32. For
a ~lange with a wall thickness of 1/16 inch a round opening a~
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 o~ pas~ageway 23 and out through disoharge
opening 3~, without significantly reducing the e~ectiveness
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 i9 related to the thickness o~ the wall
throu~h 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 o~ the dialyzer construction of Fig. 1 is
that such dialyzers are readily manufactured with more uniform
dialysis er~ectiveness than corresponding dialyzers in which
there is no partitioning and web 26 is completely omitted.
Notwithstanding the enlarged ends 14, 16 which ~erve as
dialyzate manifolds that bring the dialyæate lnto direct
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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 ~airly
5 well packed in place. Such channeling greatly reduces the
effectiveness of the dialy~is particularly through the walls
o~ those fibers that are ~ome distance laterally spaced from
the channel. When this happens with a dialyzer contalning
only a single dialyzate passageway, its e~iciency becomes so
10 poor that it genei~ly has to be di~cQrded~
Such ¢hanneling is more likely to t~ke place as the wall
thicknes~ of the hollOw ~ibers diminishes and as the ~iber
diameter decreases; these oau9e the ~ibers to be more flexible
90 that it is easier for the dialyzate to create a channel by
15 deflectlng the fibers. Wall thiaknesses o~ about 5 to about 20
microns are suitable ~or e~ecti~re use and thicknesses of` ~rom
about 10 to about 1~ microns are preferred. Fibers with
internal passageways not over about 500 microns wide, prefer-
ably rangin~ from about 100 to about 300 microns in width, are
20 ~rery effective. Cuprammonium regenerated hollow fibers of thi~
type are relatively stiff, particularly when dry, and are
acoordingly very easy to handle in the assembling of a bundle
ror insertlon in a dialyzer~ and in the insertion it~elf.
In the construction of Fig. 1 a channeling-induced drop
25 in e~i¢iency of passageway 21 can also occur, but when that
happens the dialyzate emerging from passageway 21 i9 less
loaded with contaminants so that it becomes more ef~ective in
its 9ubsequerlt passage throu~h pa~sageways 22 and 23~
In addition each of the passageways 21, 22 and 23 is
30 narrower than it would be without the web 26, and channeling
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becomes less likely in narrower passageways. Also the total
length o~ fibers contacted by the dialyzate in the construction
of Fig. 1 is three times the len~th contacted i~ web 26 were
omitted, and the efficiency loss throu~h channeling diminishes
as such length increases.
Because o~ the more reproducible greater e~iciencies
o~ the construction of Fig, 1, dialyzers having an operating
length between potting seals 56, 57, Or only about 15 centi
meters can be readily manufactured with the desired high
qualities. This small b~lk is particularly desirable,
desirable, although in general overall length~ o~ ~r~m about
6 to about 12 inches can be attractive for hospital use.
EXAMPLE 2
Figs, 5, 6, 7 and 8 illustrate a modiried dialyzer 110
pursuant to the present invention. In this dialyzer there are
three parallel dialyzer passageway~ along the lines Or Eigo 1
but the rlow Or dialyzate is arranged so that throughout its
~iber-conta¢ting path it moves on the outside o~ the individual
~ibers in a direction countercurrent to the ~low of blood or
other medium being dialyzed within the fibers.
As in the construction o~ 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 rlanges 131, 132~ 133 similar to the three ~langes
Or web 26~ and in addition also has two supplemental rlanges
134~ 135 that derine supplemental passageways 124, 125.
The bundles o~ hollow ribers are contained in passage-
ways 121, 122, 123; pa~sageways 124, 125 being unrilled 80
that they provide paths ror the dialy2ste to ~low while out
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o~ contact with the fibers.
The flow of dialyzate is controlled by appropriate
shaping of the web ~langes 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 o~ webs 134 and 135 are spaced from the
inside wall of casing end 116 and the lower ends o~ webs 131
and 132 are spaced from the inside sur~ace Or 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 ~low rate is ~airly high in the very
narrow return passageways 124, 125. Thu9 a flow rate o~ only
about one ~oot a second is generally sufficient to sweep out
gas bubbles that tend to ~orm. For slower rlow rates, as for
example when the dialyzate is discarded a~ter a siDgle passage
through the dialyzer and is not recirculated ~rom outlet 138
back to inlet 136, gas venting can be provided in the construc-
tion o~ Fig. 5.
Gas venting can be eliminated where the dialyzate is
treated to reduce gas evolution, as ~or example by boiling it
under reduced pressure before it is introduoed into the
dialyzer. This removes almost all of the dissolved gases~ and
the maintenance o~ some pressure on the dialyzate as it i9
impelled through the dialyzer acts as an additional preventive
to gas evolution.
The dialyzer casings o~ the present invention need not
be circular in cross-section but can be oval, rectangular or
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triangular if de3ired, both in their external shape as well as
ln the shape of the passageway~. Similarly, they do not have to
be perfectly linear in longitudinal direction.
EXAMPLE 3
Figs, 9 throu~h 13 illustrate a dialyzer 210 according
to the present invention which is generally triangular in
cros~-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 aæ 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 a~ a result of the frictional heating
efrects 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 correæponds to that of Figs. 5 through 8, and similar
portion~ such as partitloning web 226, passageways 221, 222 and
223 ~or reoeiving the hollow fibers, passageways 224 and 225
for dialyzate return, and inter-passage spacings 241, are
similarl~ numbered~ However~ to better seal the blood or other
dialyzand away ~rom undesired crevices and the like, covers 262
are eaoh provided with an internal sealing lip 263 shaped to
engage the potting seal 257 outæide the fiber-containing zone.
The dialyzand is thus kept from penetrating into the crevice
265 between the internal surface of the cover and external
æurface of the casing wall.
To further help with such sealing, the potting seal 257
can be arranged to project out a short distance 267, ~uch as
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1/~ inchj 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
5 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 exempli~ication,
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 ~igs. 9 through 13 without the
internal sealing lip. Internal sealing is provided in Fi~s~ 14
by having it~ end covers 462 tightly engage the outer margin of
the potting seal. Al~o instead of having the fiber-containing
passageways 421, 422 and 423 arrayed generally circumferentia~ly
around casing 410, these passageways are arranged in a simple
row all lying ln what can be considered the same thick plane.
The fiber bundles can be inserted in the dialyzer
passageways without the help of a sleeve, particularly if the
20 walls of a casing end provide a gradual taper from their large
internal bore down to the smaller bore of ¢entral 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
25 are of relatively thin wall section~ i.e. about 3 mils, so
that they do not occupy much room.
~ he 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
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readily sliding the bundles into place, after which the ca9ing
cools down an~ tightly encloses the ~ibers, thus making ror
added e~iciency~ Instead o~ an elongated sleeve to help the
fiber însertion, a single narrow length o~ plastic or even
wire oan be looped around a ~iber bundle adjacent one end, and
tied or crimped against the fibers so as to provide a tail for
the bundle. The bundl~ can then be pulled through a passageway
by ~irst pa~sing the tail through the passageway and then pull-
ing on the tail.
It is generally desirable to clean the hollow fibers ~or
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 contaot the dialyzand
or dialyzat~.
The advantages o~ partitioning are obtained when the
dialyzer is partitioned to provide only two parallel dialyzing
passageways. A very simple constructlon of this type has inlet
and outlet tubes 36, 38 on opposite sldes of the upper casing
16 with a single central web extending longitudinally the
entire length o~ the oasing 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 ~ parallel
dialysis passageways, but the use o~ more partitions takes
away some of the space ~or fibers so that the bulk of the
casing has to be increased to maintain the dialyzing
effectiveness.
The partitioning o~ the present invention simpli~ies the
mechanical handling in the manufacture o~ the dialyzer. The
reduced width of the individual pa~sageways, e.g, one to three
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centimeters, as compared to an unpartitioned dialyzer, reduces
the number of fibers per passageway and thus simpli~ies the
preparation Or the individual bundles. By way of illustration,
the task of preparing a 6000-fiber bundle for an unpartitioned
dialyzer is more complex than that o~ preparing three 2000-
fiber bundles for use in the dialyzer of Flg. 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 i9 that the
di~ferent compartments of the descrlbed 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, 90 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 effeots on the dialyzand as it passes
through the dialyzer. Indeed some of the passageways, such
as passageway 124, can be fllled 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
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compositions that harden to form thermosetting resins. ~he
potting mixture itself can for example be used as a prel~minary
dip of shallow depth~ ~ollowed by deeper potting. Also, by
maintaining slightly higher press~e in unplugged ~iber 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 bore3 can be completely eliminated. ~he 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.
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 o~ the dialyzate chamber
~rom the dlalyzand gas pressure applied over the liquid potting
composition during the potting, has a similar ef~ect. One end
o~ a ~iber bundle can accordlngly be potted a~ a time, without
the need ror the centrifugal potting apparatus.
Also the covers 61, 62 can be arranged to snap on over
the potted ends o~ the dialyzer, as shown in Fig. 5 at 161,
162 ~or example. Such covers can be relatively ~lexible and
the potted ends they snap over can be ritted 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 desalinating brackish water ~or instance,
requires membranes of relatively non-porous material such as
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polyvinyl chloride, as well RS the use of a driving pressure
grsater than the osmotic pressure and as high as practicable.
An attempt to carry out such a reverse osmosis with the cupr-
mmonium regenerated cellulose as described above, will merely
cause the brackish water to rapidly filter through the
regenerated cellulose fibers and emerge at the discharge face
of the cellulose in substantially the same condition as it
entered the entrance face.
The dialyzer construction of the present invention can
also be used with the dialyzate 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 i9 the dialyzand. However with osmosis-type
fibers, the structurQl arrangement of the present invention is
suitable for osmotic processes such as reverse osmosis~ and in
suoh use it is pre~erred to pass the fluid being treated around
the hollow fibers so that the high pressures used on such
flulds 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
o~ 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.
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