Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
P6773
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 form-
aldehyde.
~ ccording to the present teachings, there is provided a
hollow fiber dialyzer which has an elongated tubular casing
which contains partitioning that divides its interior into a
plurality of separate longitudinally-extending passageways with
di~alyzate flow directing means provided for receiving dialyzate
from an external source and for directing it to flow from one
end of the casing to the other through one of the passageways
and then back to said one casing end through another of the
passageways and so to and fro lengthwise through the other
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passageways and finally out of the casing. At least two of the
passageways have a longitudinally-extending bundle of elongated
hollow blood dialysis fibers which extend lengthwise therethrough.
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
end of the hollow fibers for delivery to an outlet. At one end
of the casing the flow directing means contains a gas by-pass
connected between successive passageways to permit gas bubbles
trapped at that end, when the dialyzer is operated with that end
up, to be discharged out of the casing without having to be
carried by the dialyzate to the other end.
The invention will now be described in more detail, by way
of example only, with reference to the accompanying drawings, in
which:-
F~g. 1 is an elevational view partly in section and partly
broken away, of a hollow fiber dialyzer in accordance with the
present invention;
F~gs. 2, 3 and 4 are sectional views of the construction of
2n Fig. 1, taken along the lines 2-2, 3-3 and 4-4, respectively;
Fig. 5 is a view similar to Fig. 1 of a modified hollow fiber
dialyzer representative of the present invention;
Figs. 6, 7 and 8 are sectional views of the construction of
Fig. 5 taken along the lines 6-6, 7-7 and 8-8, respectively;
Figs. 9, 10, 11 and 12 are views similar to Figs. 1, 2, 3 and
4 of a further modified dialyzer typical of the present invention;
Fig. 13 is a sectional view of a cap suitable for use with
the construction of Fig. 9; and
Figs. 14, 15 and 16 are views similar to Figs. 1, 2 and 3 of
yet another embodiment of the present invention.
The followinq examples illustrate very desirable manners
of preparing hollow fiber dialyzers in accordance
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uith the present application.
EXAMPLE 1
A dialysis casing such as shown at 10 in F~g. 1 and
molded or cemented together from polycarbonate or polystyrene
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 being
of enlarged bore having internal diameters about 1~7/6 inches.
The tubular length of the interior of the casing i8 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 dischargs tube 38 leads out from end 16.
Web 26 has flow control means at each end ~ , 16 arranged
90 that fluid entering inlet 36 flows upwardly through passage-
way 21 from end 14 to end 16, then at end 16 moves ~rom the top
o~ pa~sageway 21 to the top of passageway 22, then downwardly
through passageway 22 to lower end 14 where it then transfers
to the bottom o~ 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 againstthe outer wall of the caslng throughout the length of lower
end 14 as well as throughout the length of the intermedia~e
portion 12, but not at the upper end 16. Instead at that
upper end flange 31 is cut out as shown at 40 to provid0 a
~low through space 41 that thus opens between the upper ends
o~ passageways 21 and 22.
Flange 32 is similarly shaped in an opposite sense 80
that at its lower portion it provides an edge 50 spaced from
the lowest point o~ casing end ll~ to provide a flow-through
~0 space 51 between the lower ends of passageways 22 and 23.
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A batch of hollow cupram~onium regenerated cellulose
~iber3 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 ~rom a
plurality of spools in parallel strands, cut to a length of
about 9 inches and carerully cleaned. As generally supplied
these fibers are made by egtruding cu;prammonium cellulo~e
solution through an annular die into a regenerating bath wh~le
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 3uch as
glycerine, preferably leaving about 5~ of the softening agent
by weight of the clean fiber. This softening is not essen-
tial but helps guard the fibers against breakage or damage
during subsequent handling, and does not detract from the
effectiveness by ~hich 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 passageways 21, 22, 23J 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 ~illed
sleeve, narrow end first, into one o~ 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 of~ the other ends of the fibers.
IVhen all the passageways are filled with fibers, the
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potting ean be started. At each end o~ the casing each bundle
o~ fibers pro~eots a short distance. ~Each o~ these pro~ecting
ends i9 dlpped in melted oarnauba wax ~which is then permitted
to solidi~y after the carnauba wax has penstrated a very short
distanca into all o~ the individual f'ibers. ~he casing is than
clamped longitudinallg between potting heads connected to a
potting compound container as illustrated in Fig. 19 of' Patent
3,442,oo2, and centrifuged as also indicated in that patent
while the uncured liquid freshly 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 cement mixture as described in Patent 3,442,oo2, or
a hardenable polysiloxane liquid or other settable resin.
When a hardenable poly~iloxane liquid with a curing
agent such as chlorplatinic acid is used, the centrif'uging is
conducted at about 350 g while the mixture is hea~ed~ and a~ter
about 1/2 hour at 150F. the potting mixture is cured to the
point that it no longer f'lows. The potting heads are then
unclamped and removed, and the curing completed by holding the
dialyzer in an air oven at 150F f`or two hours. A~ter that
the potting mixture is a cleanly cutting solid and a sharp
metal blade i3 used to cut the potting mixture f'lush with the
open ends 14, 16 o~ the casing. This leaves the construction
as illustrated in Fig. 1, the potting composition being sho~n
at 56 and 57. Covers 61, 62 each equipped with a f`low
connection 64, 65 are then fitted to the casing ends 14, 16
as by ~elding or cementing~ although they can also be
threaded in placs lf' desired. The construction ls then
oomplete and only needs a flushing through to remove the water-
soluble sof'tening aKent ~rom the inside of the hollow fibers
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be~ore it is placed in service. The dialyzers can be stored
either be~ore or a~ter washing out the softening agent, without
significantly a~fecting its dialysis properties.
l~hen 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, arld a supply o~ blood to
be dialyzed connected to inlet 65 with a blood return to outlet
64. In use bubbles of air or other gases can form in the
dialyzate and tend to rise toward the upper end 16 of 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 uith the dialysis~ a small bleed
59 i3 shown as provlded at the upper end of web ~lange 32, For
a flange with a wall thickness o~ 1/16 inch a round opening as
little as 1/2 millimeter in diam3ter will enable the gas
trapped at the above-mentioned ends to readily make its way
into the upper end o~ passageway 23 and out through discharge
opening 38, without signi~icantly reducing the er~ectiveness
o~ the dialysis. The gas vent can even be m~de slightly
smaller as ~or example 0.3 mm. in diameter. The optimum
width o~ the vent is related to the thickness o~ 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 ~eature Or the dialyzer construction o~ Fig. 1 is
that such dialyzers are readily manu~actured with more uni~orm
dialysis ef~ectiYeness than corresponding dialyzers in which
there is no partitioning and web 26 is completely omitted.
Notuithstanding the enlarged ends 14, 16 which serve as
dialyzate mani~olds that bring the dialyzate into direct
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contact with the outer layers o~ ~iber3 in the ~lber bundles~
the dialyzate has a tendenc~ to make iLts way throu~h one end
of the dialyzer to the other through the e~sie~t path and thus
~ind and e~tablish a channel, even when the flbers are ~airly
well packed in place. Such channeli~g greatly reduces the
e~fectiveness Or the dialysis particularly through the walls
o~ those fibers that are some distance laterally spaced ~rom
the channel. When this happens with Q dialyzer oontaining
only a single dialyzate passageway~ lt3 ef~iciency becomes so
poor that it generally has to be discarded.
Such channeling i9 mors likely to ta~e place as the wall
thickness of the hollow fiber~ diminishes and as the fiber
diameter decreases; these cause the fibers to be mors flexible
90 that lt is easier for the dialyzate to create a channel by
de~lecting the fibers. l~all thicknesses of about 5 to about 20
microns are suitable for e~ective use and thioknesses of ~rom
about 10 to about 15 microns are pre~erred. Fibers with
internal passageways not over about 500 m~crons wide, prerer-
ably ranging ~rom about 100 to about 300 m~crons in widthg are
very effective. Cuprammonium regenerated hollow ~ibers of this
type are relatively sti~f, particularly when dry~ and are
accordingly very ea~y to handle in the assembling of a bundle
~or insertion in a dialyzer, and in the insertion it~el~.
In the con3truction o~ Fig. 1 a channeling-induced drop
in erficiency of passageway 21 can also occur, but when that
happens the dialyzate emerging from pa~sageway 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
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bscome~ less likely in narrower passageways. Also the total
length of ~ibers contacted by the dialyzate in the construction
o~ ~ig. 1 is three times the length oontacted ~ web 26 were
omitted, and the e~ficiency loss through channeling diminishes
as such length increases.
Because of the more reproducible greater e~iciencies
of the construction o~ Fig~ 1, dialyzers having an operating
length between potting seals 56, 57, of only about 15 centi-
meters can be readily man~actured with the desired high
qualities. This small bulk is particularly desirable,
desirable, although in general overall lengths of ~rom about
6 to about 12 inches can be attractive for hospital US9-
EXAMPLE 2
Figs. 5, 6, 7 and 8 illustrate a modified dialyzer 110
pursuant to the present invention. In this dialyzer there arethree parallel dialyzer passageways along the lines o~ Fig, 1
but the ~low o~ dialyzate is arranged so that throughout its
fiber-contacting path it mo~es on the outside o~ the individual
fibers in a direction countercurrent to the ~low o~ blood or
other medium being d-ialyzed within the ~ibers.
As in the construction o~ Fig~ lg dialyzer 110 has a
central tubular section 112 with enlarged ends 1141 116 and
with a partitioning web 126 inserted or molded in section 112.
Web 126 has ~langss 131, 132, 133 similar to the three flanges
~ web 26, and in a~ldition also has two supplemental ~langes
134, 135 that de~ine supplemental passageways 12ll, 125.
~ he bundle~ o~ hollow ~ibers are contained in passage-
ways 121, 122, 123; passageways 124, 125 being unfilled so
that they provide paths ~or the dialyzate to flow while out
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of contact with the fibers.
The flow of dialyzate is controlled by approprlate
shaping of the web flanges in the construction o~ Fig. 5 so
that it enters and flows upwardly first through passage 121
then downwardly through passage 124 then back upwardly through
passage~iay 122 returning this tlme to the bottom via passageway
125, and ~inally completing the dialysis by an upward travel
through passageway 123 and discharge at outlet 138. For this
result, the upper ends o~ webs 13~ and ~35 are spaced ~rom the
inside wall of casing end 116 and the lower ends o~ webs 131
and 132 are spaced ~rom 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 foot a second i9 generally su~icient to sweep out
gas bubbles that tend to form. For slower flow rates, as ror
example when the dialyzate is discarded after a si~gle passage
through the dialyzer and is not recirculated ~rom outlet 138
20 back to inlet 136, gas venting can be provided in the construc- -
tion of Fig. 5 .
Gas venting can be eliminated ~here 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 i9
lmpelled 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 o~al, rectangular or
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6773
triangular i~ desired, both in their external shape as well as
in the shape o~ the passageways. Similarly, they do not have to
be per~ectly linear in longitudinal direction.
EXAMPLE 3
Figs. 9 through 13 illustrate a dialyzer 210 according
to the present invention which ls generally triangular in
cross-section, particularly at its ends 214~ 2165 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 o~ the cover ruse as a result Or the frictional heating
e~ects o~ the vibration between them, and weld together making
a very e~ective M uid-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 ~ibers, 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 ~rom undesired crevices and the like, covers 262
are each provided with an internal sealing lip 263 shap~d to
engage the potting seal 257 outside the ~iber-containing zone.
The dialyzand is thus kept ~rom penetrating into the crevice
265 between the internal sur~ace of the cover and external
sur~ace o~ the casing wall.
To ~urther help with such sealing, the potting seal 257
can be arranged to project out a short distance 267, such as
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1/8 inch, beyond the casing end.
EXAMPLE 4
Figs. 14, 15 and 16 illustrate a dialyzer Ll12 having a
gen_rally rectangular configuration both in its external aspect
as well as in its passageways. Such a configuration makes
better use ol space and can contain more fibers than other
com~igurations having the same overall dimensions.
The construction and operation of this exempli~ication,
as ~Jell 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. Al30 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 dial-yzer
passageways without the help of a sleeve, particularly i~ 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 le~t in tht~ dialyzer in position around the bundles.
This alternative i9 particularly desirable when the sleeves
are o~ relatively thin wall section, i.e. about 3 mils, so
that they do not occupy much room.
The insertion of the ~iber bundles is also made easier
if this is done when the casings are hot. The heat expands
the casing and thus provides a little more room for more
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j773
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 ~ores 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 of fibers per passageway and thus simpli~ies the
preparation of the individual bundles. By way o~ illustration,
the task o~ preparing a 6000 fibsr bundle ~or an unpartitioned
dialyzer is more complex than that o~ preparing three 2000-
~iber bundles for use in the dialyzer of Fig. 1 or Figo 5 or
Fig~ 9.
The ~lber~containing passageways can also be double
tapered as illustrated at 211 in Fig. 9 30 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
~rom being de~lected by the ~low around them, thus reducing
the tendency to channelling.
Another ~eature o~ the present invention is that the
di~erent compartments o~ the described dialyzers need not be
used ~or the same function. One of the compartments can ~or
example be used to hold an absorbent such as activated charcoal
or the lil~e~ instead of fibers, so as to absorb impurities or
other undesirable ingredients in the dialyzand. Di~ferent
kinds o~ fibers can be used in di~ferent passageways to obtain
different dialysis e~fects on the dialyzand as it passes
through the dialyzer. Indeed some o~ the passageways, such
as passageway 124, can be ~illed with absorbent ~or the purpose
o~ treating the dialyzate as it moves through the dialyzer and
better condition the dialyzate ~or 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 form thermosetting resins. The
potting mixture itself can for example be used as a prel~Dinary
dip of shallow depth~ follo~ed by deeper potting. Also, by
maintaining slightly higher pressure in unplug~ed 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 eliminatedv 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 un-
necessary.
'~hile centrifugal force applied to the liquid potting
mixture helps assure that such mixture thoroughly impregnates
all crevices and pores around and between the fibers and in
this 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 time9 without
the need ~or 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 the dialysis uses fibers whose walls are
extremely porous, much too porous for use in osmosis. ~his
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
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polyvinyl chloride, as well as the use of a driving pressure
graater than the osmotic pressure and as high as praoticable.
An attempt to oarry out suoh a reverse osmosis with the oupr-
mmonium regenerated oellulose as described above, will merely
cause the brackish water to rapidly filter through the
regenerated cellulose fibers and emerge at the disoharge 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 dialy7ate 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 is the dialyzand. However with osmosiswtype
fibers, the structural arrangement o~ the present invention is
5 suitable for osmotic processes such as reverse osmosis3 and in
such use it is pre~erred to pass the fluid being treated around
the hollo~t fibers so that the high pressures used on such
fluids in reverse osmosis is applied to the exteriors of the
f~bers. ~iber 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 man~ modifications and variations of the
25 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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