Note: Descriptions are shown in the official language in which they were submitted.
677~
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 con-
taining partitioning which divides the interior into at least
three separate longitudinally-extending passageways with dialy-
zate 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 length-
wise through the other passageways and finally out of the casing.
7~
At least three of the passageways each have a longitudinally-
extending bundle of elongated hollow blood dialysis fibers extend-
ing lengthwise therethrough and means are provided connected to
deliver blood to be dialyzed from an inlet to the fiber ends of
each of the bundles at the same end of the casing and to receive
the blood from the other ends of the hollow fibers for delivery
to an outlet. The passageways which have the bundles of fibers
are generally circular in cross-section throughout their length
between the dialyzate entrance and exit ends and are clustered
around a common centerline.
The invention will now be described in more detail, by way
of example only r 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
Fi~g, 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;
Fi~g. 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 polycarbonate or polystyrene
resin, is ~irst provided. This casing has an over-all length
of about 7-1/2 inches with its lntermediate portion 12 having
sn internal diameter of 1-3/8 inches, each end 14, 16 being
Or enlarged bore having internal diameters about 1-7/8 inches.
The tubular length o~ the interior of the casing is divided
into three lndividual passageways 21~ 22, 23 by an axial web 26
of three rlanges~ 31, 32 and 33. An inlet tube 36 opens into
enlarged end 14, and a discharge tube 38 leads out from end 160
~ .Veb 26 has ~low control means at each end ~ , 16 arranged
so that ~luid entering lnlet 36 ~lows upwardly through passage-
way 21 ~rom and 14 to end 16, then at end 16 moveq ~rom the top
o~ passageway 21 to the top o~ passageway 22, then down~vardly
through passageway 22 to lower end ~ where it then transfers
to the bottom o~ passageway 23 along which it moves upwardly
to end 16 for discharge through outlet 38. To ef~ect this
flow control, flange 31 is arranged as a barrier seal againstthe outer wall of the casing throughout the length o~ 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 rlange 31 is cut out as shown at 40 to provide a
~low-through space 41 that thus opens between the upper ends
Or 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 ~rom
the lowest point of casing end 14 to provide a flow-through
space 51 between the lower ends of passageways 22 and 23,
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A batch o~ hollow cuprammonium regenerated cellulose
~ibers having a wall thickness of about 12 microns plus or
minus 2 microns and an internal diameter o~ about 200 microns
plus or minus 50 microns is unspooled, pre~erably ~rom a
plurality of spools in parallel strands~ cut to a length of
about 9 inches and carefully cleaned. As generally supplied
thess fibers are made by extruding cuprammonium cellulose
solution through an annular die into a regenerating bath while
introducing a water-immiscible liquid into the bore o~ the
hollow extrudate. A typioal water-insoluble liquid is
isopropylmyristate. After regeneration is completed care~ul
~ashing with isopropanol removes such liquid. The lnteriors
of the fibers can then be wet with a softening agent such as
glycerine, preferably leaving about 5% of the softening agent
b~ weight o~ the clean ~iber. This softening is not e~sen-
tial but helps guard the ~ibers against breakage or damage
during subsequent handling, and does not detract from the
effectiveness by which the ~ibers are sealed into the casing
10.
A bundle of two to three thousand ~ibers so prepared is
then inserted into one o~ the passageways 21, 22, 23, and
additional bundles in each of the remaining passageways. This
insertion can be e~pedited by first sliding over the bundle a
tapered sleeve of polyethylene, then introducing the ~illed
sleeve, narro~,7 end first~ into one o~ the passageways, and
~inally pulling the sleeve o~ the introduced bundle. At
the narrow end of t;he 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 fibers.
When all the passagelNays are ~illed wlth flbers, the
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6 ~ 7~
potting can be ~tarted. At each end o~ the casing each bundle
o~ ~ibers projects a short distance. Each of these pro~ecting
ends i3 dlpped in melted carnauba wax which is then permitted
to solidi~y after the carnauba wax has penetrated a very short
distance into all o~ the individual fîbers. The casing is then
clamped longitudinally between potting heads connected to a
potting compound container as illustrated in Fig. 19 o~ Patent
3,442,oo2, and centrifuged as also indicated in that patent
while the uncured liquid freghly mixed potting mixture i9
poured into the potting compound container. This mixture can
be a polyurethane prepolymer resin with a chain extender, or
an epo~y csment mixture as desoribed in Patent 3,442,oo2, or
a hardenable polysiloxane liquid or other settable resin.
When a hardenable polysiloxane liquid with a curing
15 agent quch as chlorplatinic acid is used, the centri~uging iq
conducted at about 350 g while the mixture is hea~ed~ and after
about 1/2 hour at 150F. the potting mixture is cured to the
point that it no longer ~lo~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 is a cleanly cutting solid and a sharp
metal blade is used to cut the potting mixture ~lush with the
open ends 14, 16 o~ the casing. This leaves the construction
as illustrated in Fig. 1, the potting composition being shoun
at 56 and 57, Covers 61, 62 each equipped with a ~low
connection 64, 65 are then fitted to the casing ends 14, 16
as by welding or cementing, although they can also be
threaded in place lf` desired. The construction is then
oomplete and only needs a ~lushing through to remove the wator-
soluble so~tenlng agent from the lnslde o~ the hollow ~1bers
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before it is placed in ~ervice, The dialyzers can be stored
either before or after washing out the softening agent, without
significantly affecting its dialysis properties.
l~hen the dialyzer is used it is generally held with end
5 16 up, a source of dialyzate is connected to inlet 36,
discharge 38 is cor~ected to wa3te, and a supply of blood to
be dialyzed connected to inlet 65 with a blood return to outlet
64i In use bubbles of air or other gases can form in the
dialyzate and tend to rise toward the upper end 16 o~ the
di~lyzer. 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 i3 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
15 little as 1/2 millimeter in diameter will enable the gas
trapped at the abo~e-mentioned ends to readily make its way
into the upper end of passageway 23 and out through dischar~e
opening 38~ without significantly 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 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 o~ the dialyzer construction of Fig. 1 is
that sush dialyzers are readily manufactured with more uniform
dialysis effectiveness than corresponding dialyzers in which
there is no partiti.oning and web 26 is completely omitted D
Notwithstanding the enlarged ends 14, 16 which serve as
dialyzate manifolds that bring the dialyzate into direct
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contact with the outer layers o~ ~lber~ in the ~ber 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
~lnd and establish a ¢hannel, e~en when the riberQ are ~airly
well packed ~n place. Such channeling greQtly reduces the
e~ectiveness of the dialysis particularly through the wall~
of those ~ibers that are some distance laterally spa~ad ~rom
the channel. When this happens with Q dialyzer oontaining
only a single dialyzate passageway~ its ef~iciency becomes so
poor that it generally has to be di3carded.
Such channeling is more likely to take place as the wall
thickness of the hollow fibers diminishes and as the riber
diameter decreases; these oause the fibers to be more ~lexible
so that it is easier ~or the dialyzate to create a channel by
de~lecting the ribers. Wall thicknesses of about 5 to about 20
microns are suitable ~or effecti~e use and thicknesses o~ ~rom
about 10 to about 15 microns are preferred, Fibers with
internal passageway3 not over about 500 microns wide, prerer-
ably ranging from about 100 to about 300 miorons ln width, are
very e~ecti~e. Cuprammonium reganerated hollow ~ibers o~ this
type are relatively stif~, particularly when dry~ and are
accordingly very easy to handle in the assembling o~ a bundle
for insertion in a dialyzer~ and in the insertion ~t3el~.
In the construction of Fig. 1 a channeling-induced drop
in efficiency o~ passageway 21 can also occur, but when that
happens the dialyzate emerging ~rom pa3sagewa~ 21 is le3s
loaded with contaminailts so that it becomes more e~ective in
its sub3equent passage through pa3sageways 22 and 23.
In addition each of the passageways 21, 22 and 23 is
narrower than it would be without the web 26, and channeling
~9~
becomes less likely in narrower passa~eways. Also the total
length of fibers contacted by the dialyzate in the construction
of Fig. 1 is three times the length contacted ~ web 26 were
omitted, and the efficiency loss through channeling diminishe3
as such length increases,
Because of the more reproducible greater efficiencies
Or the construction Or Figo 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 desirable,
desirable, although in general overall lengths of from about
6 to about 12 inches can be attractive for hospital useO
EXAMPLE 2
Figs. 5, 6, 7 and 8 illustrate a modified dialyzer 110
15 pursuant to the present invention~ In this dialyzer there are
three parallel dialyzer passaæeways along the lines of Figo 1
but the flow of dialyzate is arranged so that throughout its
fiber-contacting path it moves on the outside of the individual
ribers in a direction countercurrent to the rlow of blood or
other medium being d-ialyzed within the ~ibers.
As in the construction of Fig. 1, dialyzer 110 has a
central tubular seotion 112 with enlarged ends 114, 115 and
with a partitioning web 126 inserted or molded in section 112~
Web 126 has flanges 131, 132 ~ 133 similar to the three flanges
o~ web 26, and in acldition also has two supplemental ~lange~
134, 135 that define supplemental passageways 12LI, 125.
The bundles oY hollow fibers are contained ln passage-
ways 121, 122, 123; passageways 124, 125 being unfilled 90
that they provide paths for the dialyzate to flow while out
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of contact with the fibers.
The flo~ of dialyzate is controlled by appropriat0
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 12~ 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 lo~Jer 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 o~ 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 sl~gle passage
through the dialyzer and i9 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 is
treated to reduce gas evolution, as ~or example by boiling it
under reduced pressure before it is introduced into the
dialyzer. This removes almost all o~ 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 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
in the shape of the passageways. Similarly, thay do not have to
be parfectly linear in longitudinal direction.
EX~MPLE 3
Fi~s. 9 through 13 illustrate a dialyzer 210 according
to the present invention ~vhich is gene~ally triangular in
cross-section, particularly at its ends 214, 2160 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 onl~ be about 15 to about 20 mils
high that helps in ~elding 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 ~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 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, co~ers 262
are each provided with an internal sealing lip 26~ 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 o~ the cover and external
surface o~ the casing wall.
To further help with such sealing, the potting seal 257
can be arranged to project out a short distanc0 267, such as
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1/8 inch, beyond the casing end.
EXAMPLE 4
Figs. 14, 15 and 16 illustrate a dlalyzer 412 having a
generally rectangular confi~;uration both in its external aspect
5 as well as in its passageuvays. Such a configuration makes
better use of space and can contain more ~ibers than other
configurations having the same overall dimensions.
The construction and operation of this exemplification,
as well as the numbering of its parts, i~ 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 ~ig~ 14
by having its end covers 462 tightly engage the outer margin of
the potting seal. Also instead o~ having the ~iber-containing
passageways 421, 422 and 423 arrayed generally circumferentiaL~y
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
20 wallq 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 ths dialyzer in position around the bundles.
This alternative is particularly desirable when the sleeves
25 ~re of relatively thin wall section3 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 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
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centimeters, as compared to an unpartitioned dialyzsr, reduces
the number of fiber~ per passagaray and thus simpli~ies the
preparation Or the individual bundles. By way o~ illustrationg
the task Or preparing a 6000-fiber bun~le 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~ ~ or
Fig. 9.
The ~lber-containing passageways can also be double
tapered as ~llustrated at 211 in Fig. 9 90 that they provide a
constriction ~n their central portions. Such a constriction of
about 1/2 to 1 millimeter helps grip the fibers and ~eep them
from being deflected by the flow around them, thus reducing
the tendency to channellin~
Another feature of the present invention is that the
di~ferent 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 RS activated charcoal
or the li!~e, 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 ~illed with absorbent for the purpose
of treating the dialyzate as it moves through the dialyzer and
better condition the dialyzate ror its passage through the
remaining fiber-containing passageways.
The potting Or the fiber ends can be accomplished with
techniques other than that described above. Thus the
preliminary dip o~ the ~ibers to plug their bores can be into
melted resin-modi~ied waxes or thermoplastic resins or
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compositions that harden to rorm thermosetting resins. The
potting mixture itself can ~or example be used as a preliminary
dip of shallow depth9 ~ollowed 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 ~iber ends when they
are of fusible nature, and in this way make a prior dip un-
necessary.
'~hile centrifugal ~orce applied to the liquid potting
mixture helps assure that such mixture thoroughly impregnates
all crevices and pores around and between the ~ibers and in
this way assures thorough sealing o~ the dialyzate chamber
from the dialyzand gas pressure applied over the liquid potting
composition during the potting, has a similar e~ect. One end
o~ a ~iber bundle can accordingl~ be potted at a time, without
the need for the centri~ugal pott~ng 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 ~lexible 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 i9 to be distinguished ~rom
osmosis in that the dialysis uses ~ibers 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 desAlinatlng brackish water for instance,
requires membranes of relatively non-porous material such as
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polyvinyl chloride, as well as the use o~ 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 ~ace.
The dialyzer construction of the present invention can
al~o be used with the dialyzate passing through the bores o~
the hollow ~lbers and the dialyzand moving along the outside
of the fibers, although this arrangement is not desirable
here blood is the dialyzand. However ~ith 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 ~ibers so that the high pressures used on such
fluid3 in reverse osmosis is applied to the exteriors of the
~ibers. 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 ~he oxygenation
o~ blood where silicone fibers are preferred.
Obviously many modifications and variatlons 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 other~ise than as specifically described.
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