Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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Thi~ lnvention relate~ to hemodlalyzers and ~r.ore
partlcularly to ~m~ll light~e~ght hemodlalyzers having a hl~h
surfa~ce area to blood prlming volume which utllize ~eml
permeable membrane~ sealed to a generally r~gld case. PortR
arè provided in the case BO as to permlt blood and dial~-
~ate ~low through the hemodlalyzer,
Prevlou~ly consid~ra.ble dl~iculty had been expor~
ien¢~d ln the productlon o~ ~mall lightweight h~modialyzer8,
partieularly wlth regard to o~tainlng conslstently good
10 u ltraf'lltratlon rates, hlgh wet rUpture strenæth, absQn~e
o~ leakage durlng clinical u~e, a~d ab~ence o~ torn m~m
bran2s during manu~acturing. The~e and oth~r dl~lcult~3
o~ the prior art have been oY~r¢ome a~cordln~ to the pre~-
ent ~nventlon.
Aocording to certain aspects o~ the present invention, a small
efficient lightweight hemodialyzer is produoed which includes a
semlpermeable membrane anchored ror eeal~ng purpo~es to a
~elatively rigld case. The ca~e i8 provlded ~ith port~ to
permit the pa~sage of blood and dialysate, pr~ferably ln
20 counter¢urrent ~low, through the hemodialyzer. The mem-
br~ne i8 generally a cellulo~iG ox other ~em~perm~able
membrane which ls subJect to dlmen~lonal ~h.nge~ wlth
~han~e~ in its water cont~nt. In ganeral the m~mbran~s used
~n the hemodlalyz~rs shrlnk ln all dlmen~ion~ a~ thelr
wa~er content decreases. ~he pore~ o~ the membrane~ de
~rease in slze in an irreveraible proces~ a~ khe watex~
~ont~nt of ~he membranes de¢rea~e~. Al~o, adJacerlt layer~
of membrane tend to ~tick together lP the membran0~ are
allowed to dry in ~itu ln the d~alyzer. qhi~ alo~0~ the
30 blood channel~ in ~ome in3tance3. ~ub~equ~nt Wet'Ging and
applicatlon of n~gativ~ pressure ko the dialy~ate slde
occaslonally 1~ not su~iclent to pull the adhered membrane
layer~ ap~rt. Thu~, thare i~ a ~ubstantlal decrease in the
s~
capacity of the dialyzer due to the closed blood channels.
The membrane is pre~erably folded into a plural-
ity of pleats so as to define a stack of membrane having a
generally rectangular cross section and a compact configur-
ation which permits~ wlth suitable spacing elements; the
flow of dlalysate on one side of the membrane and blood on
the other. Flow takes place tn capillary flow channels.
The ends and edges of the pleated membrane are sealed to
the inner surfaces of the case so as to dlrect the flow of
10 blood and dialysate9 respectively, through the thin sheet-
llke passageways formed by the pleats of semipermeable
membrane material. The areas of the stack of membrane
which are adjacent to the ports are not sealed so as to
permit the Ingress of fluid to and the egress of fluld
from the t~in channels whlch are formed in the stack of
film. In sealing the ends and edges of the stack of pleated
membrane so as to force the fluid flow through the
stack, fhe stack is anchored to the inner surfaces of the
case.
When the moisture content of the film Is not con-
trolled and the cellulostc or other film is anchored or
sealed to the generally rigld case9 the wet rupture strength
of the f~lm is considerably less than what it should theo-
retlcally be. Also, unexplained leaks occur very frequently
dur7ng clinical usage. Ultraflltration rates vary from one
apparently Identical hemodlalyzer unit to another and are
considerably lower than what they should theoretlcally be.
Manufacturing dlf~iculttes are experienced in that the
membrane occastonally tears or breaks whlle being handled.
30 Occasionally durlng storage the rigld cases crack or deform.
When the moisture content of the membrane, and
particularly cellulosic membranes9 is maintained at a
value which is approxlmately in equillbrium with air having
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a relative hu~idity of at least about 46 percent and prefer-
ably at least about 50 percent, the ultrafiltration rates
are generally consistent; the wet burst strength improves
dramatically; no more cracks or deformations are observed
in the cases; and the clinical leaking o~ the hemodialyæers
is virtually eliminated as is the tendency of the membrane
to break and tear during manufacturing.
Thus, in a broad aspect the present invention
provides a hemodialyzer comprising: a substantially rigid
case including a preformed shell member having blood ports
and dialysate ports therein, said case being divided along a
parting line into two parts, each of said parts having
a generally trapezoidal shaped cross section with said parting
line extending at about the larger base of each of said parts.
A pair of wedge elements is received within said case,
the inner wall.s of said shell member and said wed~ing
elements together defining a generally rectangular cavity,
each of the cross sections of said wedge elements being
generally in the form of an o~tuse triangle. The wedge
elements are positioned on opposite sides of said case
with the apices of said triangles at about said parting line,
the legs of said triangles extending generally parallel with
the adjacent inner walls of said case/ and the bases of said
triangles extending generally perpendicular to said parting
; line.
There is acellulosic semipermeable membrane ~olded
in a plurality of pleats to define a stacl~ of dialyzing mem-
brane material having a generally rectangular cross section
and including a plurality of generally parallel p.lanar
blood and dialysate flow channels defined by said pleats
and opening respectively on opposite channel opening sides
~2~S~
of said stack. The opposite sides of said stack which
extend generally parallel to said channels are confined
between said wedge elements. The last pleat on each side
of said stack extends between and is sealed to said wedge
element and said adjacent inner wall.
Preferably said case includes means for
reinforcing said case at a portion at said parting line.
Also preferably the case includes a lap joint at said
parting line at opposite ends of said case.
In another aspect the present invention provides
a hemodialyzer comprising: a substantially rigid case including
a preformed shell membex, at least one preformed wedging
element, and a stack of dialyzing membrane, said shell member
having blood ports and dialysate ports therein and being
divided along a parting line into two parts, said wedging
element extending generally perpendicular to said parting
line. The inner walls of said shell member and said wedging
element together define a generally rectangular cavity for
receiving said stack of dialyzing membxane material. The
shell member and wedging element having wedgedly coacting
surfaces adapted to wedgedly coact to restrain and seal said
stack and prevent the application of substantial shearing
forces to said dialyzing membrane material as said two
parts are brought together along said par~ing line.
A preferred embodiment of such a hemodialyzer
includes a~sealant sealing said stack of dialyzing
membrane material to said case means to prevent the intermix-
ing of blood and dialysate~
Another preferred embodiment of such a hemo-
dialyzer includes at least one generally planar semipermeablemembrane confined within said rigid case, a flexible sealant
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sealing at least two of the edges of said membrane to
said rigid case.
Another preferred embodiment of such a hemo-
dialyzer includes lock means for coacting with said shell
member and wedging element to hold said case in said assembled
form.
Another preferred embodiment of such a hemo-
dialyzer wherein said shell member includes at least one
sealant injection port for injecting initially fluid
sealant into said case, and means for reinforcing said
parting line adjacent said sealant in~ection port to confine
said fluid sealant inside said case.
Another preferred embodiment of such a hemo-
dialyæer inc1udIng alignment means for coacting with
said shell member and wedging element to align the parts of
said shell member in proper relationship as said two
parts are brought together along said parting line.
In a further preferred embodiment such a
hemodialyer is provided wherein said stack of dialyzing
membrane includes a plurality of semipermea~le membrane
panels arran~ed so as to define a blood 1OW ch~nnel on
one side of each said panel and dialysa~e flow channel on
the other side of each said panel, a dialysate flow channel,
said suppor~ member including a plurality of first elongated
elements spaced apart from one another extending generally
parallel to one another in about a first plane and a
plurality of second elongated elements spaced apart from one
another extending generally parallel to one another in about
a second plane, said first and second planes extending
adjacent and generally parallel to one another and said first
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elongated elements extending in a different direction
from said second elongated elements.
In a further aspect the present invention provides
a hemodialyzer comprising: a substantially rigid case having
blood ports and dialysate por~s and including a shell member
and at least one wedging element assembled together, said
shell member and said element having wedgedly coacting sur~aces,
said shell member and said element being prefromed prior to
being assembled. There is a semipermeable membrane folded
in a plurality of pleats and confined within said case, a
last pleat of said membrane extending between and sealed
to said coacting surfaces.
In another aspect the present invention provides
a device comprising: a substantially rigid case including
a preformed shell member having inlet and outlet ports and
at least one preformed wedging element, said shell member
and said wedging element ha~ wed~y coacting surfaces. There is a
semipermeable nembrane folded in a plurality of pleats and confined within
said case, a last pleat of said m~brane ex~ ng between and sealed
to said ooating surfaoes.
In still a further aspest the presentinvention provides
a process of manufacturing a hemodialyzer comprising:
providing a case having initially separable shell portions
and wedging elements, said wedging elements being adapted
to wedgedly coact with said initially separable shell portions
during the assembly of said case, and said shell portions
and wedging elements being preformed to a solid state prior
to said selecting. The case is adapted to receive and
contain a stack of semipermeable membrane material. ~he
process further comprises providing a stack of semipermeable
membrane material and confining said stack between said wedg-
ing elements to produce a confined stack. The confined
3Q stack is inserted into said initially separable shell portions,
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Whereby said wedging elements coact wedgedly with said
one initially separable shell portion to permit said hemo-
dialyzer to be assembled without suhjecting said semiper-
meable membrane material to substantial sh2aring forces.
In order to obtaln the advantages of thl~ inven-
tion, it i~ neces~ary tha~ the water c:ontent o~ the mem-
brane in the hemodialyzer be ~ain~a~ned at a value ~h~ch
prevent~ the membrane from ~hrlnk~ng to any ~lgnlr1~ant
degree. Shrlnkage ls ¢on~ldered slgni~cant ~hen lt ~n-
creases the ken~ion of the membrane3 ~n the h~modialyzer tothe polnt where the wet bur~t ~trength decreaae~ by more
than approxlma~el~ lOO millimeters of mercury pres~ure
from ths~ wet burst ~trength exhlblted by a hemodlalyz~r
in which no shrinkage has o¢curred ~rom it~ a~ manu~actured
dlmen510ns. Preferably the water aontent of the me~bran~
iB malntalned at a Yalue Which prevents the membrane rrom
~hrinklng to any signlficant degree ~rom the time lk 1
manufactured untll the tlme a hemodlalyæer which ln~or-
porates th0 ~ilm is u~ed. Thus, in the pre~erred spera
20 tlon the ~ilm iB manufactured to a ¢ompleted ~ta~e con~ain-
lr~; the desired moi~ture content and i5 then stored~ tran~-
ported, formed lnto a h~modlalyzer ~ahich 1~ agaln stored
and tran~ported to the ~l~e o~ end u~e, all ~ithout any
~i~nl~lcant change in the moi~ture conkent o ~ the membrane .
Pre~erably the cellulo~îc membrane~ utllized
ac~ordlng to the teaching~ o~ the preserlt lnventlon ar~
~anufactured by a cuprammonlu~n proce~s. In general the
cuprammonium pro¢e~3 ~or the manu~acture o:~ cellulo~i¢ ~ilm
includes dlasolving cot~on or wood pulp in an ammoniacal
~opper ~olutlon which i3 ln3ected through a ~11t ori~lc~
~ 3d -
5~
into a ~ettlng bath o~ dilute ~ul~urlc acid. The pre3ent
lnvention is applicable to celluloslc ~ilm manufactured by
the vi~cose process; however, generally hemodialy~er~ whlch
are manu~actured utilizing cellulosic ~ilms made by the
vis¢ose process do not produce a~ satlsfactory a clinlcal
result a3 do those hemodialyzers which utllize cellulosic
~ilm~ manufactured by the cuprammonium proce~s.
The oellulo3ic films u~ed according to the teach-
lng~ of the pre~ent inventlon include those havlng thick~
ne~se3 ranglng ~rom about 10 to 20 micron~, although some-
what khinner and thicker ~ilms ma~ be used i~ deæired.
The~e membran~e are capable of removlng both toxlna and
drug~ ~rom blood.
In general~ a sealant i3 u3ed to seal the ends
and sldes of the generally planar, parallel blood and
dlalysate ~low channels wlkhln the ~tack o~ membrane3.
Thls sealing 18 provided, except in the area of the port~)
90 that the blood and dialy~ate are prevented from rlowlng
around the edge~ o~ the membrane ~o a~ to become ~nter-
mixed. Also, the ~luld3 are prevented ~rom ~'lowing betweenthe stack and the case in areas where no signl~icant
dialy~is can take place. No dialysis takes place between
~luidæ that bypa3s khe ~tack. The sealant ~or both the
shunt ~ealing and the blood-dialysate ~ealing 1~ applled
in the liquid ~kate and flows to fill the ~pace between
the ~ideæ and ends o~ the stack o~ membrane and the ca~e
and conform~ to both the membrane and the ca~e. Pre~er~
ably~ the ~ealant doe~ not readily wet the membrane ~o that
the menlscu~ ~ormed in the opening~ Or the ~low channel~
will be smooth and blunt rather than ~harp and thin. Each
lndlvidual pleat o~' membrane iæ anchored solidly to the
ca~e by the cured ln ~itu æealant at each o~ it~ four
edge~. Any 3hrinkage o~ the membrane wlll place the
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membrane in tenslon so as to decrease its wet rupture
strength. If the shrinkage is great enough, the membrane
will rupture or the case will crack or deform under the
force of the result~ng tension. The use o~ a relatlvely
~lexible sealant~ such as a polyurethane makerial, will
permit the accommodation o~ a slightly greater amount o~
shrinkage than will the use o~ a relakively rlgld sealant,
such as an epoxy materlal. Pre~erably the sealant is one
which is flexible and extensible and undergoes elastlc
de~ormation under the loads encountered ln the hemodialy-
zer. The sealant need not adhere strongl~ or at all to the
membrane because the membran~ takes up water and swells
during useJ thus ef~ectlng a tight seal wherever lt ls
oonfined within a body of cured so~id sealant. I~ the seal-
ant i~ not adhered to the membrane, khe hemodialyzer wlll be
able to withstand somewhat higher pressures because the
membrane can move sllghtly to distribute load~ as neces-
saryJ and the jun¢ture between the membrane and the non~
wetting sealant at the blood and dialysate ~low channels
provides a smoothly contoured support ~or the membrane.
The sealant should be one that will not crack under bendtng
or tenslle loads.
Pre~erably the sealant is possessed o~ thlxotroplc
characterlstics so that it penetrates unl~ormly lnto the
~tack but is prevented ~rom belng pulled by caplllary at-
tra¢tion into the channels. T'nixotrophy also pre~ent~ the
sealant from ~lowing into the channels due to the action o~
gravity. Uslng a sealant which ha~ thlxotroplc aharacter-
istics al30 enables the achlevement of a smooth blunt
30 meniscus in the channels ~o that sharp points and edges
whl¢h might tend to cut the membrane are avolded.
The speol~ic embodlment~ lllustrated in khe draw-
lngs are prov-lded ~or the purpose ~ illu~tration only and
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not to limit the lnventlon.
Referring particularly to the drawings, there i~
illustrated:
FIG. 1, a perspectlve view ~ a hemodlalyzer case
according to the present inventioll;
FIG~ 2, a perspective vlew o~ a ~tack o~ ~emi-
permeable membrane materlal ~olded into a plurality o~
pleats to define respective blood and dialysate ~low chan-
nel~ and adapted to be conta~ned withln the case lllustrated
in ~lg. l;
FIG. 3, a per3pective view slmllar to Flg. 2 ~how-
lng sealant applied to the stack~
FIG. 4, a broken cros~-~ect~onal view taken along
llne 4-LI o~ Fig . 3 j
FIG. 5, an exploded elevational view ef an a~sem-
bled hemodialyzer;
~I~. 6, a broken cro~s section vlew taken along
llne 6~6 o~ Fig. 3 and including the hemodlalyzer case and
sealant;
2Q FIG. 7, a broken cros~-sectional vlew taken along
line 7~7 ln Fig. 3 through a dlalysate ~low channel and
includ~ng the hemodialyzer case and ~ealant;
FIG. 8g a perspective exploded vlew of a further
embodiment of a hemodialyzer caæe includlng snap lock and
allgnment elements;
FIG. 9, a broken cro~-sectional view o~ the embod-
iment o~ Flg. 8;
FI~. 10, a peræpective view ~ a membrane ~epar-
ator;
3 FIG. 11, a par~pective view o~ a rurther embodl-
ment o~ a membrane ~eparator;
FIG. 12, a cro~-sectlonal viaw of a further em-
bodiment o~ a hemodialyzer ca~e in whlch a ~ealant receptacle
~ 5.~
ls provlded at the parting line o~ the case halves;
FIG. 13J a broken elevational view ~ a further
embodlmen~ having a lap Joint reinrorcemsnt at the case
end~;
FIG. 14, an exploded cross-sectional view ~ the
embodiment illu~trated in ~g. 13~
FIG. 15, a cros~-~ectional vlew taken along llne
15-15 in Fig. 13;
FIG. 16, a ¢ross-sectional view taken along line
16-16 in Flg. 13,
FIG. 17, a cross~sectional vlew of a two ~tag~
port seal;
F~G. 18, a view similar to Fig. 17 ~howlng the
port ~eal ln the sealed oon~iguratlon;
FIG. 19, a croæs sectional view taken through
line 19-19 of Fig. 17; and
FI~. ~0, a perspective elevatlonal vlew ~ a ~ur-
ther embodiment of a wedging element.
Referring particularly to the drawing~, there is
2~ illu~trated a hemodialyzer case 10 and a stack o~ 3emi- -
permeable membrane 12 ~olded in~o a plu~allty of ploat~
a~d adapted to be contalned within hemodialyzer case 10.
Case 10 1~ provided with an inlet blood port 14 and an out-
let blood port 16. Dialy~ate inlet port 18 and dialysat2
outle~ port 20 are provlded so a~ to pexmit countercurrent
flow o~ blood and dialy~ate through the hemodialyzer. The
re peotlve blood and dlalysate ports lnclude plenum cham
bers ~ormed in the ease immedlately over the membrane so
: as to permit unl~orm di~trlbution o~ fluld a¢ross the
`~ 30 hemodlalyzer. The respective blood and dialy~ate ports
a~e desi~ned wi~h dl~erent coupling con~guration3 so
that lt is impossible to connect them improperly to a kid-
ney dlaly~is machine. The hemodialyzer ¢ase 10 in¢ludes a
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shell 22 which is divided along a partlng line 24 into a
~ir3t part 26 and a second part 28. Parts 26 and 28 are in
the ~orm of regular trapezoids~ the larger ba~e of each
part occurr~ng at the parting llne 24~ Fir t wedging ele-
ment 30 and second wedging element 32 are provided within
shell 22 to act as wedging members to compres~ the ~tack
12 and allow assembly o~ the hemodlalyzer without ~ub~e¢t-
lng the membrane to shearing stresse~, and to provide for
the sealing of the last pleat o~ membrane 34. The wedging
elements 30 and 32, re~pectively, have obtuse triangular
cross ~ections with the apex o~ the triangle extendlng at
about the parting line 24 and the base of the triangle
~orming one wall og a generally rectangular cavity into
which stack 12 ~s received. Membrane 34 i3 folded into
pleats ~o as to define generally planar parallel blood
flow channels 36 and dialysate flow channels 38. Dlaly-
sate permeable separators 40 are positioned within the
dialy~ate flow channels 38 so as to provide support and
permit the ~ormation of thin flow channels 36 and 38 wlthin
stack 12. The blood flow channels are o~ c~plllary s~æe
when blood is ~lowing through them.
Stack 12 i~ recelved within the rectangular cavity
de~ined by ~hell 22 and wedging elements 30 and 32 and i8
8 ealed therein by sealant 42~ lllu3trated particularly in
Figs. 3, 6, and 7. Membrane 3~ ls continuous from where
the last pleat 44 overlaps one wedging ~ur~ace o~ ~lr~t
wedging elemént 30 to last pleat 46 wh~ch overlap~ one
o~ the wedglng sur~aces of khe ~econd wedging element 32.
In order to prevent the intermixing o~ the dialy~te and
blood, lt i9 nece~sary to ~eal flrst end 48 and ~econd end
50 o~ stack 12 and last pleat~ 44 and 46 so that there 1~
no ~en path between the blood flow channel3 and the dlaly~
sa~e ~low channel~. The sealant penetrates the channels
at ends 48 and 50, and the blood ~low channels 36 on ~lrst
channel opening side 52 and khe dialysate flow channels 38
on second channel openlng slde 54. The membrane i8 shorter
than the interior length o~ the case so as to provide a
space ~or sealant to flow uniformly into the ends of the
stackJ thus ~nsuring complete encapsulation of' the membrane
edges. The last pleats 44 and 46 are sealed wlth ~ealant
at the ~irst channel parallel side 56 and second cha~nel
parallel slde 58 as shown in sllghtly expanded form in,
10 ~or exampley Fig. 5. The last pleat 46 is trapped between
wedging surface ~0 on secon~ wedging element 32 and wedg-
ing ~ur~ace 62 on ~he flr~t part 26 o~ shell 22. Wedging
~urfaces 60 and 62 extend coangularly so that when last
pleat 46 is trapped between the surfaces it is supported
on both sides by the sur~aces. Sealant 42 ls applied on
both side~ of last pleat 46 so that the edges of this pleat
are sealed to prevent fluids from passlng around them.
La~t pleat 44 is likewise trapped between the coa~ting
wedging sur~aces o~ first wedglng element 30 and the flrst
20 part 26 of shell 22 and encapsulated with sealant. The
sealant fills the voids between khe base walls o~ parts 26
and 28 and the respective channel opening sldes o~ stack
12 so as to prsvent M uid from shunting past the ~tack
through these voids. Wedglng ~ur~ace~ 64 and 66, respec=
tlvely~ extend generally coangularly with one another and
are in contact wlth one another7 although they are shown
sllghtly separated in Fig. 6 ~or the purpo~es of lllustra-
tlon.
In the completely manufactured form khe dlalyzing
me~branes are arranged as a plurality of clo~ely ~paced
generally planar rectangular membrane~. F,ach lndividual
planar membrane is anchored on all f'our o~ its edges,
excepk ad~acent the ports, to the rigld case. The struckure
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is arranged so that blood ~lows in caplllary flow thin
sheet~like channels on one side of the membrane, and dialy~
sate ~lows in capillary ~low on 'che opposite slde of the
membrane through an lnltlally somewhat thicker sheet-llke
channel. The membranes are supported so as to wikhstand
substantial transmembrane pressures without bursting or
shi~t~ng ou~ of position by an open mesh support member on
one side o r each membrane. The support members are on
the dialysate side ~ t~le membranes so a~ to support the
membranes against the higher pressures on the blood slde.
The support members are anchored by dire¢t c~ntack with the
sealant on the second channel openlng side 54 and lndirectly
through the membrane on the ~ir~t channel opening s~de 52.
The relatively stiff support members prevent the membrane~
from shi~ting so as to open a few large ~low channels
through which all o~ the ~luid would ~low.
The wedging sur~aceæ provided by the shell and
wedging elements are utllized in the construction of the
hemodialy~er. Tl~e sem~permeable membrane 34 is withdrawn
~rom the ~ubstantially vapor proo~-contalner in whlch it
has been transported and stored from lks slte o~ manu~ac-
ture, and it ig ~olded in a humidlty controlled environ-
ment into a plurali~ of pleats with the dialy3ate per-
meable separators 40 in alternate pleats. The resultant
stack 12 of semipermeable membrane is then placed between
wedglng elements 30 ~nd 32, a~ ~hown for example in Fig. 5.
A ~ealant material ln the liquid phas~ i~ applied ~o the
inner sur~aces o~ æhell 22 ln those area~ where sealing is
required. Also, sealant ls applied at least to sur:~aces
30 60 and 68 and to ~ur~a¢e~ 66 and 70, if desired. ~he stack
o~ semipermeable membrane 12 including the membrane 34/
the dialysate permeable separators 40 and the wedging
elements 30 and 32 is inserted into second part 28 of shell
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22. The coactlon between the wedging surfaces 66 and 70
and the adjacent outwardly tapered coangular surfaces o~
second sllell part 28 resul~s in t~e assembly of the stack
12 to the lateral dlmension that it wlll occupy in khe
completed hemodialyzer, The ~irst part 26 of shell 22 is
then placed over the stack unkll the two halves o~ 22 are
brought together at parting line 2~ wikhout sub~ecting the
membrane to shear~ng ~orces. The case halves are held
together by a band Or tape brldging the partlng llne 24 and
10 extending substantially entirely around the oase, S~alant
is then in~e~ted into the void space at the ends 48 and 50
o~ the stack 12 so as to seal the ends of the flow channels
36 and 38. The stack is pre~erably compressed prior to
assembly~ The assembly returns slowly to lts precom-
pressed dlmensions so that when it ls compressed and im-
mediately a~sembled into the case, the assembly is easlly
accompllshed and the stack is in the compressed state with
in the case a~ter it has recovered from the preassembly
compression, This resul~s in achieving blood passages
20 having a uni~orm thickness, Because the stack 12 i~
already compres~ed wllen first part 26 o~ shell 22 ls placed
over the stack 12~ the last pleats 44 and 46 are not ~orci-
bly contacted by the adjacent outwardly tapering coangular
walls o~ the first part 26 o~ shell 22 untll khe shell
halve~ are almost in contact with one another along part-
lng line 24. In this way the la~t pleat~ 44 and 46 are not
torn by reason of the shearlng a¢tlon of one wall sliding
again~t another with the last pleats trapped therebetween,
Ther~ is enough contact between the wedglng surface~ a~ the
shell halves are drawn together wi.th the last pleats 44
and 46 krapped th~rebetween so that the last pleats are
drawn taut but not enough so that they ri~k belng torn. The
sealant is cured and the hemodialyzer ls sterilized by gas
S~
sterllizing procedures.
Referring particularly to Figs. 10 and 11l there
is illustrated two speci~ic embodiments of dialysate per-
meable separators. Dialy~ate permeable separator 40 is
composed of round elongated ~ilaments 72 and 74g respec-
tively. The ~ilaments 72 exten~ generally in the same plane
and are approximately parallel to one another. The ~ila-
ments 74 extend generall~ at approximately right an~les to
filaments 72. Fila~ents 74 are generally ln a second plane
which extends adjacent to and parallel with the plane ln
whtch ~llaments 72 are located. In operation the membrane
on either side o~ dialysate permeable separator 40 tends
to depress into the spaces between the respective ~ilaments
72 and 74. Under pressure surges on the blood side the
membranes meet at about the midpoint between the plane~
which contain the respective ~llaments. The membranes
meet und~r pressure surges at about the plane which in
clude~ the contact points between the respective filaments.
Apparentl~, the membranes are forced into contact with one
another ln the interstices of the dialysate permeable
separator 40 only during pressure surge3 or when the preæ-
sure on the blood ~ide i5 considerably higher than it is
on the dlalysate side o~ the membranes. The dialysate
permeable separator indlcated generally at 76 in Fig. 11
i~ a ~urther embodlment in which the elongated ~ilaments
have a generally triangular cross section with contact
betw0en the ~ilaments taking place between the bases o~ the
~ilaments. The arrangement and operation of the dialy~ate
permeable separator 75 i~ generally the same as that de~
scribed with reference to dialysate permeable separator 40.
Referring partlcularly to ~ig. 8, a ~urther
embodlment of a hemodlalyzer case lndicated generally at
82 is lllus~rated in which the lap ~olnt structure~ are
-12-
5~
provided at the respective ends of the case, and alignment
and snap lock features are provided ko ~acilltate the align-
ment of the parts of the case during assembly and to retain
the parts in assembled configuration. The hemodialyzer
case 82 lncludes a shell 83 wh-Lch is divlded inko two
parts along a parting line 84. The ~irst part o~ shell 83
is indicated at 86 and the second part at 88. A ~lrst
wedging element 90 is received within shell 83 on one side
o~ the hemodialyzer case 82 and a second wedging element
10 92 ~g received withln shell 83 ln a position opposed to
~irst wedging element 90. The arrangement and interrela-
tionshlp~ between the elements of the hemodialyzer case 82
are generally the same as those described prevlously wlth
re~erence to hemodialyzer case 10.
A snap lock an~ alignment structure is provided
in hemodialyzer ca~e 82 and include~ locking tabs 94 whiGh
project outwardly from the respective wedging faces or
sur~ace~ o~ flrst and second wedging element~ 90 and 92,
respectivel~. The locking tab~ 94 are positioned so that
20 when the case halves 86 and 88 are brought together in
~ully assembled relationship the locking tabs will proJect
into and interlock with grooves 96. As the case halves are
advanced towards one another the locking tabs 94 are re-
ceived ~n and guided by alignment ramps 98 so that as the
ca3e parts are drawn together they are automatically
aligned by the intèraction of~ locking tabs 94 with align~
ment ramps 98.
Sealant ln~ection port~ 100 are provided at oppo
~ite ends of hemodialyzer ¢ase 82. Ports 100 permit the
30 ln~ection o~ sealant into the ends o~ a stack o~ semiper-
meable membrane con~ined wlthin case 82 so as to en¢apsu-
late the ends of the stack of semipermeable membrane and
prevent the intermLxing o~ blood and dialy~ate. Lap ~oint~
~3
,
102 are provided at the ends o~ case 82 so a~ to rein~orce
the ends and confine the sealant. The lap Jolnts 102 are
provided at parting line 84 and include an outer tongue
104 which is provided in ~lrst part 86 and i~ recelved in a
mating groove in second part 88. An inner ton~ue 106
proJects ~rom second part 88 into a matlng groove ln first
part 86. The lap ~olnt~ 102 extend acros~ the end~ o~ the
hemodialyzer and for a short distance along the sldes of
the hemodlalyzer.
Re~erring particularly to Figs. 17, 18 and 19,
there is illustrated an embodiment of a port seal which ls
applicable to both the blood and dlaly~ate ports ~lthough
~or the purposes of illustratlon only blood port 16 i3
lllu~trated. The port seal indicated generally at 108 in-
cl~des a sleeve 110 whlch is adapted to be slidably received
ln snug, ~terileg sealing relation3hlp on male ~ittlng
112. Male fltting 112 is adapted ~or connection to a kidney
dialysis machlne. Sleeve 110 has a ported end 114 ln
which an inner port 116 is axially located. A two stage
cap 118 is slidably received over the outer exterior end
o~ sleeve 110. ~wo stage cap 118 i~ provided with an
outer port 120 and a port plug 122 which 1~ axially
aligned with lnner por~ 116. Two stage cap 118 i3 snugly
reoelved in sliding sealing relatlon~hlp with the exterlor
outer end of sleeve llO. A ring 124 is provided on the
cylindrical interior wall o~ two stage cap 118. Ring 124
~.~ positioned ~o that lt is ln cooperating relation~hip
with ~lrst stage groove lZ6 on the exterior cylindrlcal
~ur~ace of ~leeve 110 when the port seal i~ in a first
open con~lguration, and with second ~tage groove 128 when
port seal 108 is in a ~econd closed conflguration. When
port ~eal 108 1~ po~itioned over male fitting 112J the
~ittlng is protected ~rom contamination and i~ maintained
32~
7n a sterlle condition. When two stage cap 118 1~ ln the
open con~lguration, as shown for example in Fig. 17~ ambl~
ent fluld is ~ree to pass through outer port 120, inner
port 116, and into ~he interior of the hemodialyzer through
male fitt~ng 112. When two ~tage cap 118 is moved to the
closed conf~gurat~on, as ~llustrated ~or example in Fig.
18, the port plug 122 is received in inner port 116 in a
snug sterile fit so thak fluid cannot pass through inner
port 115 in e~ther direction. The rit between port plug
122 and inner port 116 is su~ficiently snug so that there
is no leakage of eith0r llquld or gaseous phase fluid~
through thi~ port when the port seal lOi is in the closed
conf~guration. I~ de~ired, a bacterla impervious ~ilter
(not illustrated) may be u~ed in outer port 120. Sleeve
110 is provided with an enlarged area 130 80 as to permit
its being gra~ped and lnserted over male ~itting 112 with-
out risk o~ moving two stage cap 118 from ~ts open to its
clo~ed con~iguratlon. Rings 132 and 134 ar~ provlded on
the intar~or cylindr~cal wall of sleeve 110 so a~ to pro~
20 vide a sterile seal with male fitking 112.
Referrlng particularly to Fig. 20 there is lllu~-
trated an additlonal embodiment o~ a wedging ~lement.
Wedging element 136 is provided on the planar ~tack side
thereo~ with hal~ round ridge~ 138. Ridges 138 extend
generally at an angle o~ approximately 45 to the longitu-
dlnal axis o~ the wedging element 136. Hal~ round ridges
138 conveniently replace the la~t dlalysate permeable
separator on each side o~ the ~tack of membrane materlal.
The hal~ round ridge~ 138 provide a depth from the outer~
30 mo~t point on the ridge to the flat subsurface o~ the wedg-
ing element 136 which is approximately one-hal~ that depth
provided by a ~ull dialysate perrneable separator. In the
structure where a dialysate permeable separator i9 next to
~3~5-
2~
the innerface Or a wedging element the membrane which ls
supported by that separator tends to be forced under pres~
sure surges by the blood to stretch ~or the ~ull dept'n o~
the separator unt~l it comes into contact with the æurface
o~ the wedging element. Thus, the last full ~embrane is
sometimes required to stretch twice as ~ar as are the other
membranes within the stack. The other membranes need only
stretch half w~y through the depth of the separator because
they are met by a membrane on the other side which is like-
wise stretclling hal~ way through the depth of the separator.By using the half round ridges 138 on the sur~ace o~ the
wedging element 136 in place o~ a ~ull separator, the last
full membrane on each slde o~ the stack o~ membrane is only
required to s~retch the same amount as the other membranss.
This avolds the possibility that exce~sive stress will be
placed on the last ~ull membrane on each slde of the stack
under unusual operating condltions.
Re~ rring particularly to Fig. 12, there is illus~
trated an embodiment of the wedglng element in which the
apex o~ the triangle ~ormed by the wedglng sur~aces has
been removed. Wedging element 140 is provided at the apex
o~ the wedgin~ element with a planar surface 14~. When
planar sur~ace 142 i5 brought into operative cooperative
relatlonship with the case halves 85 and 88, a small
sealant receptacle is provided ad~acent parting l~ne 84
so that any excess sealant which may be on the wedglng
; sur~aces o~ wedging element 140 has a place to collect
without interferlng with the closure o* the case.
The entire manu~acturing o~ the hemodialyzer ~rom
the tlme the semipermeable membrane iæ removed ~rom itæ
vapor tight container to the time when the manufacture and
sterillzatlon of the hemodial~Jzer is complete is accom-
plished under conditlons whic,h maintain the moisture
-16
Z~
content o~ the semipermeable membrane at about the desired
values, The blood ports and dialysate ports are sealed
w~kh removable sealing members so that durlng transporta-
tlon and storage of the completed hemodialyzer there will
be no sub tantial change in the moisture content of the
membrane, Under conditions o~ constant moisture content
the dimenslons o~ the membrane an~; thus the stresses in
the case and membrane~ will not change from those that
were in existence at the time the manu~acture o~ the hemo-
lO dialyzer was completed. The s~resses ln the hemodlalyzeras manu~actured are low. As a result the hemodialyzer ig
capable o~ w~thstanding relatively high pressures ~or short
perlods Or time during use. Suc~ elevated pressures o~ten
occur for short perlods of time during the normal usage o~
a hemodlalyzer. In general the short term wet rupture
strength o~ the present hemodlalyzer is in excess o~ about
lg200 milli~eters of mercury~ utilizing an 11.5 micron
thlck semipermeable membrane.
One example o~ a hemodialyzer manu~actured accord-
2~ ing to the teach~ngs o~ the present inventlon has overall
exterior dimensions o~ about 11 3/4 inches by l 3/~ inches
by 2 inche~ and weight s 338 grams. The fittings whlch
provlde for the necessary connection with a dialy is
machine pro~ect somewhat beyond these dimQnsions so as to
provide a convenient means ~or coupling the hemodialyzer to
the dialysis mach-lne. rlle rectangular cavity wh~ch re-
ceives the stack 12 within the hemodialyzer has ~lmension~
- o~ about 11 1/8 inches by 1 3/4 inches by 1 3/8 lnches.
~he obtuse angle at the apex o~ the trlangular shaped
3 wedging elements ls abou~ 165 degrees. The shell part~ are
constructed o~ polycarbonate havlng a generally trapezoidal
cross-sectlonal shape w~th the larger base of the trapezoid
belng at the parting llne. The wall~ o~ the shell parts
25~L
taper outwardly towards the partin~ llne coang~larly with
the adjacent surfaces oF the wedging elements at an angle
of about 7 degrees. The membrane has a total area of about
1.4 square meters and a thickness of about 11.5 mlcrons.
The membrane is a cellulosic material manufactured by the
cuprammonium process. It is folded from side to side to
provide 62 dialysate channels and 61 blood channels. A
flexTbie urethane sealant having a Shore A hardness of 65
i 5 used to seal the hemodialyzer. The sealant is appl7ed
10 In the llquTd form and cured to the solid state in sltu.
The sealant does not thoroughly wet the membrane. The
dialysate permeable separators are an open mesh nonwoven
polypropylene material in which round polypropylene fila-
ments havlng a thickness of approxlmately 0.010 Inch are
latd over and adhered to one another so that they intersect
at an angle of about 90 degrees. The dialysate permeable
separators are arranged so that the indlvidual filaments
extend at an angle of approximately 45 to the longitudinal
axls of the hemodtalyzer. The filaments are adhered to one
20 another at their intersections without belng interwoven
so that all of the filaments which extend ganerally in the
sa~e dtrectlon are located in about the same plane and
those fllaments which extend at right anqles thareto are
located in a second plane immediately adJacent to the first
plane. The open spaces between the filaments are generaliy
rectangular and are approximately 0.063 Inch wide. The
lateral dimensions of the blood and dialysa~e flow channels
in the completed sealed unii are about 10 3/4 Inches by
I 1/2 inches. Abou-t 1.2 square meters of membrane sur~ace
30 ~rea is avallable for dlalysis. hll of the fluid flow
within the ciialyzer except that which takes place immedi-
ately adJacent the ports is conflned within the stack of
membrane. The volume of blood whlch Is requlred to prl~a
-18-
=~ i
2~
the d~alyzer and which remalns ln the dlalyzer afker use lscompleted ls very small. The resldual blood volume ls about
2.2 milliliters. In use the urea clearance rate at a blood
~low rate of 200 milllliters per mlnute and a dlalysate
~low rate of 500 milllllters per minute is about 146 milll-
liters per minute. The creatlnine clearanc~ at the same
flow rate~ is about llO milliliters per minute. The pres
sure drop~ at these flow rates are lO and 20 millimeter o~
mercur~ across the blood and dialysate s~des3 respectively,
of the hemodialyzer. The ultra~iltration rate iæ about 3.0
mlllillter per hour per millimeter of mercury pressure.
The dialy~ate ls degased accordlng ko conventlonal proce-
dures before being passed through the hemodlalyzer. The
short term wet burst strength is about 1J 200 milllmeters o~
mercury transmembrane pressure.
The multiple bloGd pathways are very thin and
undulate somewhat along their length due to the configura-
tlon o~ the dlalysate permeable separator~. Th~ undulation
o~ the blood ~low pa~hways lnsure3 that the ent~re volume
of blood will be circulated into contact with the semi-
permeable membrane so that efficient dialysis takes place.
The total void volume of the dialyzer is about 310 mllli-
liters. The con~lguration and materials o~ construction
are ~uch that the hemodialyzer 1~ capable o~ being dry
sterillzed~ Also3 a gas can be used to tesk the hemo-
dialyzer for leaks. The low blood and dialysate pressure
drops acros~ the hemodialyzer makes po~sible very small
obligatory ultraflltration rates. The hemodialyzer ls oper-
ated wlth the pres~ure on the blood side higher than that
on the dialysate side so khat in the event o~ a leak dial~-
; sate will not be pumped into the pakient, Increasing the
tran~membrane pressure to 500 millimeters of' mercury re~ults
in a very high ultrafiltration rate. The clearance rates do
~2~
not decrease to a ~ignificant degree with u~age during onesingle treatment. Clearance rates apparently do decrease
somewhat i~ the hemodlalyzer is reu~ed a second time. De-
crea~lng the dialysate flow to 300 mlllillters per minute
does not result in an e~cess~ve decrease in clearance rates.
In general the materials of constructlon from
which a hemodialyzer constructed according to the present
invention ls bullt are those materials wh~ch are compatible
with blood and which are nontoxic. The sealant should be
an exten~ible material whlch has a Shore A hardness o~
~rom about 50 to 70 and preferably ~rom about 55 to 65 and
which ln the uncured 8 tate iB a thixotropic liquid. The
sealant must be curable in ~itu within the as~embled hemo-
dialyzer and must be capable o~ encapsulatlng and ~ealing
the edges of the membrane. The extensibility of the cured
sealant has a ~ubstantial ln~luence on the devicels opera-
tion. Wet burst ~trengths of from about 400 to 4~0 milli-
meters of mercury o~ pressure are encountered when the
~ealant ls a rigid epoxy material having a Shore A hardne~s
which i9 beyond the Shore A scale. The utilization o~ a
polyurethane sealant havlng a Shore A hardness of 65 in-
creases the wet burst strength to about 750 millimeters of
mer¢ury pressure. Controlllng the ambient conditions wlkh-
in the device so as to prevenk the build up o~ stresse~
al~o substantially improves the operation of the device.
Maintaining the ten~ion ln the membrane at as manu~actured
value~ until end use result~ in ~urther increasing the wet
burst ~trength to about 1,200 mlllimeters o~ mercury pres-
sure. The membrane must be a materlal which i~ o~ such a
30 character and thickne~ that it will act to permit dialysls
: ~ to occur . Preferred ~m~raneB are those cellulosic mem-
branes which have been manuf'actured according to the cupra~-
monlum proce~s; however, membranes of materlals ~uch as
~20-
2~
pol~acrylonitrile cellulose acetate polypeptide and the
likej ~or example can also be used. For those ~embranes
whlch change dimensions with changes in humidity and other
variablesj so as to set up stresses wlthin the hemodialyzer
it is necessary to maintain the moisture content and other
conditions within the hemodialyzer at approxlmately constant
values as disclosed herein. The separa~or need not be a
material to whicl~ the sealant will bond although lt should
be a material which -ls somewhat compre~sible and yet has a
memory which will allow it to return slowly to its uncom-
pre~sed state. The separator material should also be
su~ficlently ~tlf~ ~o that it is easy to handle during
assembly of the hemodialyzer. The use of a compresslble
separator which has a plastic memory advantageously permits
the stack of membrane to be compressed prlor to being in-
serted lnto the case halves. In thls way the case halves
can be drawn together without exerting shearing ~orces on
the cellulosic membrane such as would occur i~ the stack
were being progressively compressed by the wedging elements
a~ the case halves are drawn toge~her. Suitable materlals
~or construction of' the separator ~nclude, for examplej
polypropylene polyethylene, polyethylene trephthalate and
the llke. Suitable materials ~or construction of the case
lnclude relatively rigid nontoxic materials which are bond-
able by the sealant. Such suitable case materials include~
~or example, polycarbonate acrylonltrile butadine styrene
styrene acrylonitrlle, polyesters~ delrin, nylon, and the
like. The materials of construction must be mutually com~
patlble For example, the sealant must not contain mater-
ial~ which interact with the case, the separator, or the
membrane ~o as to impair 'sheir structural strength or other
useful aharacteristics.
It will be appreaiated that the prlnciple of a
21-
.
s~
two stage port seal is applicable to many diffe~ent medical
devices. It will ~urther be appreciated by those skllled
in the art that many other embodiments of the subject
matter disclosed and claimed herein in addition to those
~llustrated in the drawings can be constructed without
departing ~rom the spirlt and scope of the accompanying
claims.
~22
