Note: Descriptions are shown in the official language in which they were submitted.
SKYE
BACKGROUND OF INVENTION
This invention relates to a process and apparatus for
treating whole blood either to separate out plasma or to
oxygenate the blood in a manner to permit continuous recircula-
lion of the treater whole blood to the donor.
There are available at the present time a wide variety
; of blood oxygenation apparatus and plasmapheresis apparatus.
; Present plasmapheresis devices separate the whole blood
of a blood donor in order to recover the plasma josh then can
be given to a patient requiring a transfusion. Plasmapheresis
devices also are utilized to remove the plasma from the whole
blood of a patient suffering from diseases associated with an
excessively active immunological system that produce excess
antibodies such as systemic luaus erythematosus, myasthenia
gravies, or Good pasture's syndrome In either instance, it is
desirable to return the concentrated whole blood to the patient
or the donor since, in the former instance, such practice permits
the donor to give blood again within a period time about one
quarter of that required when the whole blood is donated. In
I the latter instance, such a practice permits treating the
patient's entire blood volume in a single treatment. In both
instances, the advantages of such a practice are obvious since
it permits either an increased quantity of donated blood per
donor or increased effective treatment of a dangerous disease.
It has been proposed to provide a method and apparatus
for extracting blood to form a plasma fraction and an enriched
blood fraction in US. patent 3,705,100. The apparatus utilizes
a reservoir for whole blood and a filtration membrane as well as
a flow directing means and a pressure generating means for
I passing the blood adjacent the membrane thereby effecting the
` " . ~2068B8
1 desired filtration. The primary disadvantage of this device is
that it is a batch device and it is incapable of continuously
treating blood prom a patient and for continuously recirculating
enriched blood to the patient. This, of course, is undesirable
since it greatly increases the time required for treating a
given volume of blood and subjects the patient to multiple
punctures in order to-obtain samples to be treated.
It also has been in the final report of NHLBI Contract
No. l-HB-6-2928, June, 1976 - April, 1979 to the American Red
Cross to utilize a blood filtration system that permits
continuous withdrawal of blood and continuous reintroduction of
enriched blood back to the patient. However, this device
requires a recirculating system or passing blood through a
channel and adjacent filter a multiplicity of times. The recur-
quilting system is required to achieve proper balance between
shear forces on the blood and pressure drop for the channel
height utilized thereby to minimize blood damager While the
desired blanch is achieved, the increased surface exposure for
the recirculating blood necessitated thereby also increases the
risk of blood damage thereby rendering the apparatus undesirable.
In addition US. patent 4l191,182 to Popovich discloses a
plasmapheresis apparatus that requires an undesirable recirculate
in system for blood in order to maintain the perceived required
shear stresses during filtration.
Membrane oxygenators are available wherein blood and
oxygen-containing gas are passed into contact on opposing
surface of a membrane and wherein oxygen is transferred through
the membrane into the blood while carbon dioxide is transferred
from the blood through the membrane into the oxygen-containing
stream. Presently available membrane oxygenators provide a
1 relatively thick blood film of generally greater than 0.2 mm.
The factor limiting efficiency in such devices is resistance
to oxygen diffusion in the blood film.
One approach to reducing this resistance is typifies by
US. patent 4,168,293 in which a woven screen is introduced
into the blood channel to induce mixing of the blood. This
approach, however, leads to blood damage and potential thrombus
formation, especially if used for long term respiratory support.
Another approach is typified by Bills et at, -
Transactions of American Society of Artificial Internal Oryans,volume XIX, 1973, page 72, which describes a furrowed membrane
and a pulsatile pumping system also intended to create mixing
within the blood channels. While potentially less damaging to
the blood than a mixing screen the device and its associated
hardware are complex and costly to manufacture. The 0.4 mm
- blood film thickness of this device is what leads to the necessity
for such measures.
It would be highly desirable to provide a membrane
device for processing blood whose blood channels approached
the dimensions of the micro circulation of the human body (less
than 0.1 mm diameter or height). The high surface to volume
ratio of such a device would allow the separation of blood into a
plasma stream and an enriched blood stream to be reintroduced
into the patient in a single pass through the device. Such a
device would minimize both blood damage and blood priming volume.
Utilized as a blood oxygenator, the high surface to
volume ratio would give inherently high efficiency. Further
increase in efficiency results from shear augmentation of
oxygen diffusion without the need for blood damaging mixing
screens or elaborate externally driven systems.
~;~06!3~3
1 SUMMARY OF Tie INVENTION
This invention provides a multi layer membrane
construction comprising a plurality of contiguous membrane units
each of which consists of two membrane layers and two spacer
layers. The spacer layers are in alternating relationship with
- the two membrane layers. In the plasmapheresis embodiment, one
spacer layer has a plurality of channels having a critical
height between about .02 and about 0.1 mm. It is desirable that
the channels have a length between 1 and about 10 cm and a
width between about .05 and 0.5 cm. This spacer layer has an
inlet means for introducing whole blood into the channels and
an outlet means for accumulating blood depleted of plasma from
the channels. The second spacer includes a plurality of channels
each of which are connected to a plasma outlet adapter to
collect plasma from-the whole blood. The membrane units are
sealed so that whole blood or plasma depleted hood is prevented
from passing into the plasma outlet.
In the blood oxygenator embodiment, one spacer layer
utilized for blood flow has a plurality of channels each of
JO which is between about 0.02 and about 0.1 on in height. The
total channel surface area for all spacer layers is between
about 0.5 my and 2.0 my The channels in a first spacer
; adjacent a first surface of a membrane layer connect an oxygen
gas inlet and à gas outlet. The channels of a second spacer
utilized for blood flow adjacent a second surface of the filter
layer connect a blood inlet and a blood outlet which are sealed
from the gas inlet and gas outlet.
In both embodiments the membrane and spacers must be
securely bonded to each other over their entire mating surface.
This bonding secures the membrane between adjacent spacer
1 elements and thus limits changes in channel height to local
membrane deflection. The width of the individual channels
represents the span over which the membrane is free to deflect
and is determined by the mechanical properties of typical
membrane materials. The combination of the above factors allows
critical control of channel heights of less than 0~1 mm.
BRIEF DESCRIPTION OF THEA DRAWINGS
Invention will be more fully described with references
to the accompanying drawings.
Fig. 1 is an exploded view of the blood plasmapheresis
filter unit of this invention.
Fig. 2 is a top view of a membrane and the first spacer
of Fig. 1 in contiguous relationship.
Fix. 3 is a top view of an alternative second spacer
construction.
Fig. 4 is a top view of an alternative second spacer
construction.
Fig. 5 is a top view of an alternative second spacer
construction.
Fig. 6 is a top view of the plasmapheresis housing of
this invention.
Fig. 7 is a cross-sectional view of the housing in
Fig. 6 taken along line 7-7.
Fig.! 8 is a cross-sectlonal view of the housing in
Fig. 6 taken along line 8-8.
Fig. 9 is an exploded view of the blood oxygenator
filter unit of this invention.
; Fig. 10 is a top view of the blood oxygenator filter
unit.
--5--
38~
,,
1 Fig. 11 is a cross-sectional view of the filter unit ox
Fig. 10 taken along line 11-11.
Fig. 12 is a cross-sectional view of the filter unit of
Fig. 10 taken along line 12-12.
DESCRIPTION OF SPECIFIC EMBODI~NTS
As shown in Fig. 1, the filter unit 10 comprises, a
first membrane 12, a second membrane 14, a first spacer 16, and
a second spacer 18. Both the first membrane 12 and the second
membrane 14 are of identical construction and are formed from
a pliable hydrophilic micro porous filter material and having an
average pore size extending in sub micrometer range from about
0.2 and 1.0 micrometers, preferably between about 0.5 and 0.7
micrometers, currently marketed by Millipore Corporation and .
identified as MF-Millipor a, Celotate~, Durapore~ (hydrophilic)
filters, Darlene filter, Pelvic filters, Solve ret filters,
and Microbe filters. Each membrane 12 and 14 is provided with
two longitudinal channels 20 and 22 and a widths channel 24.
The widths channel is not in fluid communication with eighth
JO of the channels 20 or 22. The first spacer comprises of plurality
of channels 32 which extend from edge 26 to edge 28 and an outlet
channel 30. When membranes 12 and 14 are contiguous to spacer 16,
the edges 26 and 28 coincide with the edges 25 and 27 respect-
lively. The second spacer 18 is provided with whole blood inlet
channel 34, a blood outlet 36 and a widths plasma outlet
channel 38. The second spacer 18 also is provided with interior
channels 40 which provide fluid communication with channel 42
which in turn is in fluid communication with plasma outlet
channel 38. When spacer 18 is juxtaposed to membrane 14, edges
37 and 39 coincide respectively with edges 25 and 27 of spacer 14.
1 The spacer strips 33 between channels 32 and the spacer strips
31 between the channels 40 are bonded to the next adjacent
membrane and provide the necessary support for the membranes
adjacent the channels so that membrane flexibility is con-trolled
to maintain the desired channel height.
The channels 32 in first spacer 16 should have a
particular height, width and length in order to accommodate the
normal blood flow rate from a donor so that blood can be removed
continuously while enriched blood from plasma has been removed
can be reintroduced continuously to the donor. In addition, the
channel height must be regulated so that the wall shear rate and
pressure drop are in the proper range not to cause significant.
blood damage. Accordingly, it is essential that the channels 32
in the first spacer 16 have a height between about 0.02 and
about 0.1 mm, preferably between about .06 and .09 mm. Further-
more, it is preferred that the channels 32 have a cumulative
width between about 20 and about 100 cm, an individual width
between 0.05 cm and 0.5 cm and a length between about 1 and
about 10 cm, preferably a cumulative width between about 50 and
. 20 about 70 cm, for all o-E the channels in all of the first spacers
an individual width between 0.08 and 0.12 cm, and a length
between about 4 and about 6 cm. It has been found that with
typical blood flow rate from a donor of about 60 and about
70ml/min and a typical blood outlet pressure between about 50
and about 80 mm Hug, utilization of a spacer having the channel
size of this invention, shear rates of between 1000 and 3000 sec.
can be obtained which effects substantial prevention of
hemolysis at the corresponding transmembrane pressures.
Referring to Fig. 2, the channels I of the first
spacer 16 are shown to overlap into channels 20 and 22 of membrane
I
1 14. This overlap permits introduction of whole blood into
channel 20, passage of the whole blood lengthwise along channels
32 while briny in contact with membrane 14 and removal ox plasma-
depleted blood from channels 32 through widths channel 22.
Referring to Fig. 3, the second spacer 44 can comprise
a whole blood inlet 20 which is spaced apart from channels 46 by
means of spacer width 48 so that blood in inlet 20 cannot pass
directly into channels 46 but can only move through parallel
channels 32 (see Fig. 1). Thus, only plasma which has passed
through a membrane 14 or 12 can enter channels 46. In this
configuration, the parallel channels 46 can overlap into a
widths channel 24 (see Fig. 1) or can be in fluid communique-
- lion directly with a channel for removing plasma prom the
housing (see Fig. 6). The plasma-depleted blood outlet 22 also
is insulated from parallel channels 46 by means of spacer
section 50 so -that plasma cannot be mixed with plasma-depleted
blood.
Referring to Fig. 4, the second spacer 9 can comprise
longitudinal channels 20 and 22 and parallel widths channels
JO 50 which are in fluid communication with longitudinal channel 52.
The channels 20 and 22 serve the purposes described above while
channels 50 serve to direct plasma removed from the whole
blood into channel 52 which is in fluid communication with means
for removing plasma from the housing (see Fig. 6).
Referring to Fig. 5, the second spacer 51 comprises
longitudinal channels 20 and 22 which serve the purposes
described above and an open space 4 within the central portion
of the spacer 51. The open space 24 is in fluid communication
with channel 54 which in turn is in fluid communication with a
means for removing plasma from the housing (see Fig. 6).
--8--
:~2~6~
1 Alternatively, the second spacer can comprise a woven mesh of a
polymeric fiber material so as to provide space between adjacent
membranes thereby to permit plasma flow Jo the plasma outlet.
Referring to Figs. 6, 7, and 8, the filter units of
this invention are shown in stacked relationship within a
housing 58. The whole blood inlet channel 20 of each membrane
12 and 14 and of each spacer 16 and 18 are aligned to form a
vertical channel 20 within the housing 58. Whole blood is
introduced into the channel 20 through inlet 60. The whole
blood passes along channels 32 of spacer 16 into channel 22
which is utilized to collect plasma-depleted blood. As with
channel 20, channel 22 is formed by the alignments of channel
: 22 in each of membranes 12 and 14 and spacer 18 together with
the fact that channels 32 overlap into channel 22. The housing
58 is provided with an outlet 62 which is utilized to withdraw
plasma-depleted blood from channel 22. The housing 58 is also
` provided with plasma outlet 64 which is in fluid communication .
with channel 35 which is formed by the alignments of channels
24 of membranes 12 and 14, channel 30 of spacer 16 and channel
38 ox spacer I
who I .
In oppression blood from a patient or donor enters
housing 58 through inlet 60 and passes along channels 32 of
spacer 16 widths through housing 58. While blood is passing
through channels I the membranes 12 and 14 allow passage of
plasma thrower while preventing the remainder of the whole
blood from passing there through. Similarly, whole blood is
prevented from directly entering channels 40 or spacer 18 by
means of sealing strips 48. Thus, whole blood is prevented from
entering channel 22. The plasma which enters channels 40 of
spacer 18 is directed through outlets 42 into channel 35.
-9
8~3~
1 Channel 35 is connected to outlet 64. Suitable tube means are
connected to outlets 62 and I and inlet 60 to permit withdrawal
of whole blood directly from patient or donor and reintroduction
of plasma-depleted blood directly into the patient on a
continuous one pass basis.
one
As Mooney Fig. 9, the filter unit 70 for the blood
oxygenator comprises, a first membrane 72, a second membrane
74, a first spacer 76, and a second spacer 78. Both the first
membrane 72 and a second membrane 74 are of identical construe-
lion and are formed from hydrophobic micro porous membranes swishes ~luoropore~ or Durapore~ (hydrophobic or solid film such as
polydimethylsiloxane, polyalkylsulfone or ethyl cellulose
perfluorobutyrate. Each membrane 72 and 74 is provided with two
longitudinal channels 71 and 73 and two widths channels 75 and
77. The widths channels 75 and 77 are not in fluid
communication with either of the chanrlels 71 and 73. The first
spacer 76 comprises of plurality of channels 79 which communicate
with channels 75 and 77 when membranes 72 and 74 are contiguous
to spacer 76 for passage of oxygen-containing gas through the
I filter unit 70. Channels 79 of spacer 76 overlap channels 75
and 77 when spacer 76 is contiguous to membranes 74 and 76.
The second spacer 7B is provided with interior channels 82 which
; provide fluid communication between longitudinal channels 71 and
73 when spacer 78 is juxtaposed to membranes 72 and 74 to
permit passage of blood through the filter unit 70. The spacer
strips 83 between channels 79 and 77 as well as the spacer
strips 84 between the channels 82 are bonded to the next adjacent
membranes and provide the necessary support for the membranes
adjacent the channels so that membrane flexibility is controlled
I to maintain the desired channel height.
--10--
;
I
1 The channels 82 in second spacer 78 should have a
particular height, width and length in order to accommodate the
normal blood flow rate from a patient so -that blood can be
- removed continuously while oxygen enriched blood can be
reintroduced continuously to the patient. In addition, the
channel height must be regulated so that the wall shear rate is
in the proper range to give sufficient augmentation of oxygen
transfer in the blood film. Accordingly, it is essential
that the chinless in the second spacer 78 have a height
between about 0.02 and about 0.1 mm. Fùrthe~more, it is
preferred that the channels have an individual width between
0.05 cm and 0.2 cm and a length between about l and about 10 cm,
preferably an individual width between G.08 and 0~12 cm.
When utilizing the blood oxygenator shown in Figs. I,
10~11, and 12, the filter units 70 of this invention are in
stacked relationship within a housing 80, the whole blood inlet
channel 71 is in fluid communication with channel 71. Whole
blood is introduced into the channel 71 and passes along channels
82 of spacer I intuitional 73 which is utilized to collect
oxygenated blood or removal through blood outlet 81.
In operation, whole blood from a patient enters housing
%0 through inlet 71 and passes along channels 82 of spacer 78.
While blood is passing through channels 82, the membranes 72 and
74 allow passage of oxygen there through while preventing the
blood from sassing there through. Similarly, whole blood is
prevented from directly entering channels 75 and 77 of spacer 78
by means of sealing strips 85 and 86. Oxygen enters gas inlet
87, passes into channel 75 and channels 79 and passes through
: membranes 72 and 74 into blood within channels 82. Oxygen-
depleted gas passes into channel 77 and out gas outlet 88.
2~6~8~
1 Oxygen gas is prevented prom passing directly into the blood by
means of sealing strips 89 and 90. The gas utilized generally
has a pressure of between about 100 mm Hug and 300 mm Hug above
atmospheric in order to effect transfer of oxygen in proper
concentrations without causing gas bubbling through the filter
or in the blood. mixture of oxygen with other gasses such as
COY, or No can be utilized. The oxygenated blood is directed
through outlets 81 which can be connected to suitable tube means
to permit withdrawal of whole blood directly from the patient
and reintroduction of oxygenated blood directly into the patient
on a continuous one pass basis.
I
-12-
~2V68~
1 SUPPLEMEN~RY DISCLOSURE
The inventor has subsequently discovered -that the
height of the channels of the spacer layer in the plasma
pharisees embodiment may be between 0.02 mm. and about 0.2 morn.
The length and width of the channels remain the same.
In the blood oxygenator embodiment, the inventor
has also discovered that the height of the channels of the
spacer layer may be between about-0.02 mm. and about 0.2 rum.
in height.
Referring to figure 9 of the drawings, the
inventor has discovered that it is essential t-hat the channels
82 in the second spacer 78 have a height between about 0.02 moo
and about 0.2 mm. The remaining dimensions are as per the
main disclosure.
- .
I
- 13
Jo !
