Note: Descriptions are shown in the official language in which they were submitted.
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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 formaldehyde.
According to the present invention, there is provided a
hollow fiber dialyzer which has an elongated tubular casing which
containS partitioning that divides the interior into a plurali-ty
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 an then back -through the one casing
and through another of the passageways and so to and fro length-
wise through the other passageways and finally out of the casing.
~t least two of the passageways each has a longitudinally-extend-
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ing bundle of elongated hollow blood dialysis fibers which
extend lengthwise therethrough with means connected to deliver
blood to be dialyzed from an inlet to the fiber ends of each of
the bundles at the same end of the casing and to receive the
blood from the other ends of the hollow fibers for delivery to
an outlet. Each of the passageways which have a bundle of fibers
has the fibers packed in it and the dialyzate flow directing
means further includes manifolding of enlarged cross-section to
direct dialyzate into contact with the outer layers of fibers
and in each of the bundles as the dialyzate enters each passage-
way thereby to reduce undesirable channeling of the dialyzate.
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 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 oE Fig. 9; and
Figs. 14, 15 and 16 are views similar to Figs. 1, 2 and 3 of
yet another embodiment of the present invention.
The following examples illustrate very desirable manners of
preparing hollow fiber dialyzers in accordance
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with the present application.
EXAMPLE 1
A dialysis casing such as shown at 10 in Fig. 1 and
molded or cemented together ~rom polyc,arbonate or polystgrene
5 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 belng
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 ~,veb 25
of threa flange3J 31J 32 and 33. An inlet tube 36 opens into
enlarged end 14, and a discharge tube 3~ leads out from end 16.
~ reb 26 has flow control means at each end ~4, 16 arranged
so that fluid entering inlet 36 flows upwardly through passage-
way 21 ~rom end 14 to end 16, then at end 16 moves from the top
of pa~sageway 21 to the top of passageway 22, then down~Yardly
through passageway 22 to lower end 14 where it then trans~ers
to the bottom of' passageway 23 along which it moves upwardly
to end 16 for discharge through outlet 38. To effect this
~low control, flange 31 is arranged as a barrier seal against
the outer wall OI 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 snd flange 31 is cut out as shown at 40 to provide a
~low-through space l~l that thus opens between the upper ends
of passageways 21 and 22.
Flange 32 is similarly shaped in an opposite sense 30
that at its lower portion it provides an edge 50 spaced from
the lowest point o~ casing end 14 to provide a flow through
space ~1 between the lower ends of passageways 22 and 23.
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A batch o~ hollow cupra~mon~um rsgenerated cellulose
~ibers having a wall thickness o~ about 12 microns plu3 or
minus 2 microns and an internal diameter o~ about 200 microns
plus or minus 50 microns is unspooled, pre~erably ~rom a
plurality o~ spools in parallel strands~ cut to a length o~
about 9 inches and care~ully 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-immiscible liquid into the bore of the
hollow extrudate. A typical water-insoluble liquid is
isopropylmyristate. A~ter regeneration is completed care~ul
~ashing with isopropanol removes such liquid. The lnteriors
of the fibers can then be wet with a so~tening agent such as
glycerine, preferably leaving about 5% of the so~tening agent
by weight of the clean ~iber~ This so~tening is not essen-
tial but helps guard the ~ibers against breakage or damage
during subsequent handling, and does not detract from the
e~fectiveness by which 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 passageiiays 21, 22~ 23, and
additional bundles in each of the rem~ining passageways. This
insertion can be expedited by first sliding over the bundle a
tapered sleeve of polyethylene, then introducing the ~illed
sleeve, narrow end ~irst~ into one o~ the passageways, and
~inally pulling the sleeve of~ 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 o~ the other ends o~ the ~ibers~
When all the passageway~ are ~illed with ~ibers, the
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potting can be QtartedO At each end oF the casing each bundle
o~ fibers projects a short distance. 'Each o~ these pro~ecting
end~ is dlpped in melted carnauba wax which is then permitted
to solidi~y after the carnauba wax has penetrated a very short
distance into all of the individual fibers. ~he casing iB then
clamped longitudinall~ between potting heads connec~ed to a
potting compound container as illustrated in Fig. 19 o~ Patent
3,442,oo2) and centri~uged as also indicated in that patent
whils the uncured liquid freshly mixed potting mixture i9
poursd into the potting compound container. This mixture csn
be a polyurethane prepolymer resin with a chain extender, or
an epo~y 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 curing
agent such as chlorplatinic acid is used, the centrifuging is
conducted at about 350 g while the mixture is heated 7 and after
about 1/2 hour at 150F. the potting mixture is cured to the
point that it no longer ~lows. The potting heads are then
unclamped and removed, and the curing completed by holding the
dialyzer in an air oven at 150F for two hours. A~ter that
the potting mixture is a cleanly cutting solid and a sh~rp
metal blade is used to cut the potting mixture flush with the
open ends 14, 16 o~ the casing. This leaves the construction
as illustrated in ~ig. 1, the potting composition being sho~n
at 56 and 57. Covers 61, 62 each equipped with a ~low
connection 64, 65 are then ~itted to the casing ends 14, 16
as by welding or cementing, although they can also be
threaded in place i~ desired~ The construction 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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be~ore it is placed in servioe. The dialyzers can be ~tored
either before or a~ter washing out the softening agent, without
significantly a~ecting ~ts dialysis properties.
When the dialyzer is used it is generally held with end
16 up, a source of dialyzate is conneoted to inlet 36,
discharge 38 is connected to waste, and a supply o~ blood to
be dialyzed connected to inlet 65 with a blood return to outlet
64. In use bubbles of air or other ghses can form in the
dialyzate and tend to rise toward the upper end 16 o~ 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 with the dialysis~ a small bleed
59 i9 ShO'NIl as provlded at the upper end o~ web ~lange 32. For
a flanga with a wall thickness o~ 1/16 inch a round opening as
15 little as 1/2 millimeter in diameter will enable the gas
trapped at the abo~e-mentioned ends to readily make its wa~
lnto the upper end of passageway 23 and out through discharge
opening 38, without significantly reducing the er~ectiveness
of tne dialysis. The gas vent can even be made slightly
smaller as for example 0v3 mm. in diameter~ The optimum
width of the vent is related to the thickness of the wall
through which it penetrates. For wall thiclmesses greater
than 1/16 inch the vent width is pre~erably a little larger
than 1/2 millimeter.
A feature OL the dialyzer construction of Fig. 1 is
that such dialyzers are readily manufactured with more uniform
dialysis e~ectiveness than corresponding dialyzers in which
there is no partitioning and web 26 is completely omitted.
Notwithstanding the enlarged ends 1l~, 16 which serve as
dialyzate manirolds that bring the dialyzate into direct
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contact with the outer layers o~ ~iber~ in the ~iber bundles~
the dialyzate has a tendency to make its way through one end
of the dialyzsr to the other through the easiest path and thus
find and establish a channelg even when the flbers are ~alrly
well packed in place. Such channeling greatly reduees the
e~ectlveness of the dialy~is particularly through the walls
of those ~ibers that are some distance laterally spaced from
the channel. ~nlen this happens with a dialyæer oontaining
only a single dialyzate passageway~ lts efficiency becomes 50
poor that it generally has to be discarded.
Such channeling i9 more likely to take place as the wall
thickness of the hollow fibers diminishes and as the riber
diameter decreases; these cause the ~ibers to be more fle~ible
so that it is easier ~or the dialyzate to create a channel by
de~lecting the fibers. Wall thicknesses o~ about 5 to about 20
microns are suitable ~or e~ective use ~nd thioknesses of ~rom
about 10 to about 15 microns are pre~erred. Fibers with
internal passageways not over about 500 microns wide~ pre~er-
ably ranging ~rom about 100 to about 300 microns in width~ are
very e~fective. Cuprammonium regenerated hollow fibers o~ this
type are relatively sti~f, particularly when dry~ and are
accordingly very easy to handle in the assembling o~ a bundle
~or insertion in a dialyzer~ and in the insertion itself.
In the construction o~ Fig. 1 a channeling-induced drop
ln e~ficiency o~ passageway 21 can also occur9 but when that
happens the dialyzate emerging from passageway 21 is less
loaded with contaminant~ 90 that it be¢omes more ef~ective in
lts subsequent passage through passageways 22 and 23.
In addition el~ch of the passageways 21, 22 and 23 is
narrower than lt would be without the web 26, and channeling
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becomes less likely in narrower passQgeways. Also the total
length of ~ibers contacted by the dialyzate ln the construction
o~ Fig. 1 is three times the length contacted i~ web 26 were
omitted, and the e~lciency loss through channeling diminishes
as such length lncreases.
Because of the more reproducible greater e~iciencies
of the construction of Fig. 1, dialyzers having an operating
length between potting seals 56, 57, of only about 15 centi-
meters can be readily manufactured with the desired high
qualities. This small bulk is particularly de3irable,
desirable, although in general overall lengths of from about
6 to about 12 inches can be attractlve for hospital uss.
EXAMPLE 2
Figs. 5, 6, 7 and 8 illustrate a modified dialyzer 110
pursuant to the present inventlon. In this dialyzer there are
three parallel dialyzer passageways along the lines of Fig. 1
but the flow o~ dialyzate is arranged so that throughout its
fiber-oontacting path it moves on the outside of the individual
~ibers in a direction countercurrent to the ~low o~ blood or
other medium being dialyzed within the ~ibers.
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 ~langes 131, 132, 133 ~imilar to the three ~langes
~ web 26) and in addition also has two supplemental ~lange~
134, 135 that define ~upplemental passageways 124, 125.
The bundleq of hollow ~ibers are contained in pa~sage-
ways 121, 122, 123; passageways 124, 125 being unfilled so
that they provide paths ~or the dialyzate to ~low while out
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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 ~ia passageway
125, and finally completing the dialy9is by an upward travel
through passageway 123 and discharge at outlet 138. 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 o~ 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
narrow return passageways 124, 125. Thus a flow rate of only
about one ~oot 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 construc-
tion of Fig. 5.
Gas venting can be eliminated where the dialyzate iB
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 o~ some pressure on the dialyzate as it is
impelled through the dialyzer acts as an additional preventive
to ga~ evolution.
The dialyzer casings of the present invention need not
be circular in cross-section but can be oval, rectangular or
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triangular if desired, both in their external shape as well as
ln the shape of the passagewayqO 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 invent~on 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 of the mounted cover against that ridge~
Upon vibration in this manner the ridge and the ridge-engaging
portion of the cover ruse as a result of the ~rictional 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 partitloning web 2269 passageways 221J 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 æone.
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 2673 such as
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1/8 inch, beyond the C8S ing end.
EXA~PLE 4
Figs. 14, 15 and 16 illustrate a dlalyzer 412 having a
generally rectangular configuration both in its external aspect
as well as in its passageways. Such a configuration makes
better use o, space and can contain more fibers than other
com~iguratlons having the same overall dimensions.
The conQtruction and operation of this exemplification,
as well as the numbering of its parts, i3 S imilar to that of
Figs. 1 through ~, 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
pasQageways 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 dial-yzer
passageways without the help of 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 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
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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 ad~acent one end, and
tied or crimpea 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
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centimeters, as compared to an unpartitioned dialyzer, reduces
the number o~ ~ibers per passageray and thus simpli~ies the
preparation o~ the individual bundles. By way o~ illustration,
the task of preparing a 6000~iber bundle for an unpartitioned
dialyzer is more complex than that o~ preparing three 2000-
~iber ~undles ~or use in the dialyzer of Fig. 1 or Fig. ~ 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 o~
about 1/2 to 1 millimeter helps grip the ~ibers and keep them
~rom being de~lected by the ~low around them, thus reducing
the te~dency to channelling.
Another feature of the present invention i9 that the
different compartments o~ the described dialyzers need not be
used ~or the same function. One of the compartments can for
example be used to hold an absorbent such as activated charcoal
or the lil~e, instead o~ ~ibers, so as to absorb impurities or
other undesirable ingredients in the dlalyzand. Different
kinds of ~ibers can be used in dif~erent passageways to obtain
di~ferent dialysis ef~ects on the dialyzand as it passes
through the dialyzer. Indeed some o~ the passageways, such
as passageway 124, can be filled with absorbent for the purpose
o~ treating the dialyzate as it moves through the dialyzer and
better condition the dialyzate for its passage through the
remaining fiber-containing passagewa~s.
The potting Or the ~iber ends can be accomplished with
techniques other than that described above. Thus the
preliminary dip of the ~ibers to plug their bores can be into
melted resin~modi~ied waxes or thermoplastic resins Or
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compositions that harden to form thermosetting resins. The
potting mixture itself can for example be used as a preli~inary
dip of shallow depth9 followed by deeper pottin~. Also, by
maintaining slightly higher pressure in unplugGed fiber bores
5 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 natureJ and in this ~ay make a prior dip un-
necessary.
'~hile centrifugal force applied to the liquid potting
mixture hslps assure that such mixture thoroughly impregnates
all crevices and pores around and between the fibers and in
15 this ~ay assures thorough sealing of the dialyæate 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 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 tha 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 relativel~J non-porous material such as
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polyvinyl chlorideg 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 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 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 o~ the above
teachings. It is, therefore, to be understood that within
the scope of the appended claims the invention may be
practiced otherwise than a~ specifically described.
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