Note: Descriptions are shown in the official language in which they were submitted.
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BIOLOGICAL FLUID FILTER AND SYSTEM
This application claims the benefit of U.S. provisional
patent application 60/102,973, filed October 2, 1998, which
is incorporated by reference.
TECHNICAL FIELD
This invention relates to a filter for processing a
biological fluid, more particularly, a filter that provides a
leukocyte-depleted biological fluid. Preferably, the filter
provides a biological fluid that is substantially free of
blood cells.
BACKGROUND OF THE INVENTION
Blood contains a number of components, including plasma,
platelets, red blood cells, as well as various types of white
blood cells (leukocytes). Blood components may be separated,
and further processed, for a variety of uses, particularly as
transfusion products. Illustratively, red blood cells
(typically concentrated as packed red blood cells), plasma,
. and platelets (typically concentrated as platelet
concentrate), can be separately administered to different
patients. Some components, e.g., plasma and/or platelets,
can be pooled before administration, and plasma can be
further processed, e.g., fractionated to provide enriched
components for a variety of uses.
Unfortunately, some material is undesirably present in
transfusion product. For example, while leukocytes combat
infection and engulf and digest invading microorganisms and
debris, the presence of leukocytes in transfusion products
can be undesirable, since, for example, they may cause
adverse effects (e. g., a febrile reaction) in the patient
receiving the transfusion. Additionally, platelet-containing
transfusion products and plasma-rich transfusion products
should be substantially free of red blood cells, since the
presence of a significant level of red blood cells in the
transfusion product (particularly if the transfusion products
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have been pooled) can lead to an adverse immune response by
the patient.
However, some commercially available filters have w
suffered from a number of drawbacks. For example, some
filters fail to remove the desired level and/or types of .
material, or have an undesirably large hold up volume, or
cause processing time to be increased. Alternatively, or _
additionally, the use of some filters requires a labor-
and/or time-intensive effort.
Accordingly, there is a need in the art for a filter for
use with biological fluids such as blood and blood
components, particularly for the production of plasma-rich
blood products, that minimizes the contamination of the
plasma-rich blood product by leukocytes and red blood cells.
These and other advantages of the present invention will be
apparent from the description as set forth below.
SUMMARY OF THE INVENTION
In accordance with an embodiment of the invention, a
filter device for providing a plasma-rich biological fluid
substantially free of leukocytes comprises a filter including
a first filter element and a second filter element, wherein
the first filter element comprises a porous fibrous leukocyte
depletion medium, and the second filter element, arranged
downstream of the first filter element, comprises a porous
membrane. Methods for using the filter device, and systems
including the filter device are also provided.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is an embodiment of a filter device according
to the present invention, including a cross-sectional view of
a filter having a first filter element and a second filter
element.
Figure 2 is an embodiment of a system including a filter
device according to the present invention.
SPECIFIC DESCRIPTION OF THE INVENTION
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In accordance with an embodiment of the present
invention, a filter device for processing a biological fluid
comprises a housing having an inlet and an outlet and
defining a fluid flow path between the inlet and the outlet,
a filter disposed in the housing across the fluid flow path,
the filter comprising a first filter element comprising a
porous fibrous leukocyte depletion medium having a CWST of at_
least about 70 dynes/cm, and a second filter element
comprising a porous membrane having a pore size of about 5
micrometers or less, said second filter element being
disposed downstream of the first filter element, wherein the
filter is arranged to allow plasma to pass therethrough and
substantially prevent the passage of leukocytes therethrough.
In another embodiment, a filter device for processing a
biological fluid comprises a housing having an inlet and an
outlet and defining a fluid flow path between the inlet and
the outlet, a filter disposed in the housing across the fluid
flow path, the filter comprising a first filter element
comprising a porous fibrous red cell barrier and leukocyte
depletion medium having a CWST of at least about 70 dynes/cm,
and a second filter element comprising a porous membrane
having a pore size of about 5 micrometers or less, said
second filter element being disposed downstream of the first
filter element, wherein the filter is arranged to allow
plasma to pass therethrough and substantially prevent the
passage of leukocytes therethrough.
In a preferred embodiment, the filter is arranged to
provide a substantially cell-free plasma-containing fluid.
A method for processing a biological fluid according to
an embodiment of the invention comprises passing a
leukocyte-containing plasma-rich biological fluid through a
filter device comprising a filter including a fibrous
leukocyte depletion medium and a membrane, and collecting a
filtered plasma-rich biological fluid substantially free of
leukocytes.
In accordance with another embodiment of the invention,
a method for processing a biological fluid comprises passing
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a leukocyte-containing plasma-rich biological fluid through a
filter device comprising a filter including a fibrous red
blood cell barrier medium and a membrane, and collecting a
filtered plasma-rich biological fluid substantially free of
leukocytes. ,
A method for processing a biological fluid provided by
another embodiment of the invention comprises processing a
biological fluid to provide a supernatant layer comprising a
leukocyte-containing plasma-rich fluid, and a sediment layer
comprising a red blood cell-containing fluid, passing the
leukocyte-containing plasma-rich fluid through a filter
device comprising a filter including a fibrous leukocyte
depletion medium and a membrane, and collecting a filtered
plasma-rich fluid substantially free of leukocytes.
A preferred embodiment of a method according to the
invention comprises processing a biological fluid to provide
a substantially cell-free plasma-containing fluid.
A system according to an embodiment of the invention
comprises a filter device, interposed between, and in fluid
communication with, at least two containers such as plastic
blood bags. In one preferred embodiment, the system
comprises a closed system.
As used herein a biological fluid includes any treated
or untreated fluid associated with living organisms,
particularly blood, including whole blood, warm or cold
blood, and stored or fresh blood; treated blood, such as
blood diluted with at least one physiological solution,
including but not limited to saline, nutrient, and/or
anticoagulant solutions; blood components,'such as platelet
concentrate (PC), platelet-rich plasma (PRP), platelet-poor
plasma (PPP), platelet-free plasma, plasma, components
obtained from plasma, packed red cells (PRC), transition zone
material or buffy coat (BC); blood products derived from
blood or a blood component or derived from bone marrow; red °
cells separated from plasma and resuspended in a
physiological fluid or a cryoprotective fluid; and platelets
separated from plasma and resuspended in a physiological
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fluid or a cryoprotective fluid. The biological fluid may
have been treated to remove some of the leukocytes before
being processed according to the invention. As used herein,
blood product or biological fluid refers to the components
., 5 described above, and to similar blood products or biological
fluids obtained by other means and with similar properties.
A "unit" is the quantity of biological fluid from a
donor or derived from one unit of whole blood. It may also
refer to the quantity drawn during a single donation.
Typically, the volume of a unit varies, the amount differing
from donation to donation. Multiple units of some blood
components, particularly platelets and buffy coat, may be
pooled or combined, typically by combining four or more
units.
As used herein, the term "closed" refers to a system
that allows the collection and processing (and, if desired,
the manipulation, e.g., separation of portions, separation
into components, filtration, storage, and preservation) of
biological fluid, e.g., donor blood, blood samples, and/or
blood components, without the need to compromise the
integrity of the system. A closed system can be as
originally made, or result from the connection of system
components using what are known as "sterile docking" devices.
Illustrative sterile docking devices are disclosed in U.S.
Patent Nos. 4,507,119, 4,737,214, and 4,913,.756.
Each of the components of the invention will now be
described in more detail below, wherein like components have
like reference numbers.
Figure 1 illustrated one embodiment of the filter device
100, comprising a housing 25 having an inlet 20 and an outlet
30, and defining a fluid flow path between the inlet and the
outlet, wherein a filter 10, comprising a first filter
element 1 and a second filter element 2, is disposed across
the fluid flow path.
In accordance with the invention, the filter 10 may be
configured to remove a desired amount of leukocytes.
Typically, the filter is configured to :remove greater than
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about 90%, preferably, greater than about 99%, even more
preferably, greater than about 99.9%, or more, of the
leukocytes from the plasma-rich fluid passing through the
filter. For example, the filter can be configured to provide
a filtered fluid having about 1 x 10' leukocytes or less. In
some embodiments, the filter can be configured to provide a
filtered fluid having about 1 x 10' leukocytes or less.
In one embodiment, wherein the fluid to be filtered
comprises platelet-poor-plasma, the resultant filtered fluid
has about 200 leukocytes/liter or less, preferably, about 100
leukocytes/liter or less. In some embadiments, the filtered
fluid has about 75 leukocytes/unit (e.g., a unit having a
volume of about 300 ml) or less.
Preferably, the filter is configured to prevent the
passage therethrough of a significant level of red blood
cells, and can be configured to prevent the passage
therethrough of a substantial number of platelets. In a
preferred embodiment, there should be no visible indication
(to the technician carrying out the filtration) of red blood
cells downstream of the filter. For example, there should be
no visible indication of red blood cells in the tubing
leading from the outlet of the filter device to the
downstream container. Typically, the filtered fluid (e. g.,
in the~container downstream of the filter) contains less than
about 5000 platelets/~.L. In an illustrative embodiment, the
resultant unit of filtered fluid has less than about 1 x 109
platelets. In one preferred embodiment, the resultant unit
of filtered fluid has about 1 x 10' platelets, or less.
The filter is configured to filter a suitable volume of
fluid in a suitable amount of time. For example, the filter
can be capable of filtering about 200 to about 400 ml of
fluid with a minimal effect on the overall processing time.
Illustratively, in some embodiments, the filter is capable of
filtering about 250 to about 350 ml of fluid in about 15
minutes, or less, e.g., in about 10 minutes.
In some other embodiments, the filter is capable of
filtering about 500 to about 1000 ml of fluid in about 25
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minutes, or less, preferably, about 20 minutes or less. In
one embodiment, the filter is capable of filtering about 600
to about 850 ml of fluid (e. g., a unit of apheresed plasma)
in about 18 minutes or less.
Preferably, the first element 1 of the filter 10, that
comprises a depth filter, comprises a leukocyte depletion
medium or a combined leukocyte depletion and red cell barrier_
medium, wherein at least some of the leukocytes are removed
by adsorption. In some embodiments, the first element also
removes at least some of the leukocytes by filtration.
Typically, the second element 2 of the filter l0,
comprising a membrane, more preferably a microporous
membrane, has a pore size that substantially prevents cells,
e.g., leukocytes and/or red blood cells, from passing
therethrough.
A variety of materials can be used, including synthetic
polymeric materials, to produce the porous media of the first
and second filter elements according to the invention; i.e.,
the leukocyte depletion medium, the red cell barrier medium,
the combined leukocyte depletion red cell barrier medium, and
the membrane. Suitable synthetic polymeric materials
include, for example, polybutylene terephthalate~(PBT),
polyethylene, polyethylene terephthalate (PET),
polypropylene, polymethylpentene, polyvinylidene fluoride,
polysulfone, polyethersulfone, nylon 6, nylon 66, nylon 6T,
nylon 612, nylon 11, and nylon 6 copolymers.
The first element 1, comprising at least one of a
leukocyte depletion medium, a red cell barrier medium, and a
combined leukocyte depletion red cell barrier medium,
comprises a fibrous medium, preferably a synthetic polymeric
porous fibrous medium, typically a medium prepared from melt-
blown fibers, as disclosed in, for example, U.S. Patent Nos.
4,880,548; 4,925',572, 5,152,905, 5,443,743, 5,472,621,
5,582,907, and 5,670,060. The element, which can comprise a
preform, can include a plurality of layers and/or media.
The first element 1 and/or the second element 2 can be
treated for increased efficiency in processing a biological
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fluid. For example, the first element and/or second element
may be surface modified to affect the critical wetting
surface tension (CWST), as described in, for example, the
U.S. Patents listed above.
Preferably, the first element 1 according to embodiments ,
of the invention, e.g., the leukocyte depletion medium, the
red cell barrier medium, or the combined leukocyte depletion
red cell barrier medium, has a CWST of greater than about 70
dynes/cm, more preferably, a CWST of 72 dynes or more. For
example, the medium may have a CWST in the range from about
75 dynes/cm to about 115 dynes/cm, e.g., in the range of
about 80 to about 100 dynes/cm. In some embodiments, the
medium has a CWST of about 85 dynes/cm, or greater, e.g., in
the range from about 90 to about 105 dynes/cm, or in the
range from about 85 dynes/cm to about 98 dynes/cm.
Surface characteristics of the first element and/or the
second element can be modified (e.g., to affect the CWST, to
provide a low affinity for amide-group containing materials,
to include a surface charge, e.g., a positive or negative
charge, and/or to alter the polarity or hydrophilicity of the
surface) by chemical reaction including, for example, wet or
dry oxidation, by coating or depositing a polymer on the
surface, or by a grafting reaction. Modifications include,
e.g., irradiation, a polar or charged monomer, coating and/or
curing the surface with a charged polymer, and carrying out
chemical modification to attach functional groups on the
surface. Grafting reactions may be activated by exposure to
an energy source such as gas plasma, heat, a Van der Graff
generator, ultraviolet light, electron beam, or to various
other forms of radiation, or by surface etching or deposition
using a plasma treatment. In some embodiments, the first
and/or second elements can be modified as described in, for -
example, the U.S. patents listed above.
Typically, the first element 1 has a negative zeta .
potential (e.g., in the range of about -3 to about -30
millivolts, in some embodiments, in the range of about -7 to
about -20 millivolts) at physiological pH (e.g., a pH of
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about 7 to about 7.4).
In accordance with the invention, the first element 1
may be configured to remove a desired amount of leukocytes.
Typically, the element is configured to remove greater than
about 90%, preferably, in excess of about 99%, or in excess
of about 99.9%, or more, of the leukocytes from the fluid
passing through the filter.
One embodiment of a leukocyte depletion medium suitable
for passing the plasma in about one unit of biological fluid
(e.g., for passing a plasma-rich fluid such as
platelet-poor-plasma) has, for example, a fiber surface area
of from about 0.08 to about 1.4 M~/g, and in some
embodiments, from about 0.1 to about 0.9 Mz/g. One
embodiment of an illustrative range for the relative voids
volume is about 50% to about 92%, e.g., about 60% to about
89%.
In some embodiments, the first element comprises a red
cell barrier medium, a red cell barrier medium and a
leukocyte depletion medium, or more preferably, a combined
red cell barrier leukocyte depletion medium. A red cell
barrier medium, in accordance with the present invention,
comprises a porous medium that allows the separation of a
non-red cell-containing biological fluid, such as plasma, or
a suspension of platelets and plasma, from a red
cell-containing biological fluid. The red cell barrier
medium prevents a significant level of the red
cell-containing biological fluid from entering a container
such as a satellite bag or a receiving container downstream
of the barrier medium. The red cell barrier medium may allow
the non-red cell-containing fluid to pass therethrough but
significantly slows or effectively stops the flow of
biological fluid as the red cell-containing fluid approaches
the barrier medium. For example, the red cell barrier medium
may allow a plasma-rich fluid to pass therethrough, abruptly
stopping flow when red blood cells block the medium.
By slowing the flow of the biological fluid, the barrier
medium allows the operator to manually stop the flow to
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prevent the red cell-containing biological fluid from
entering a container such as a satellite bag or a receiving
container downstream of the barrier medium, e.g., prior to a
significant level of red cells passing through the barrier
5 medium. This embodiment of the invention allows the operator ,
more time to intervene and stop the flow. For example, a
supernatant plasma-rich fluid may flow through the red cell
barrier medium at an initial rate of about 15 ml/min, but the
flow may decrease to about 5 ml/min as a sediment red
10 cell-containing fluid approaches the medium. A reduction in
flow, e.g., a 33°s reduction, may provide the operator
sufficient time to stop the flow at the appropriate time. In
some circumstances, for example, when plasma-rich fluid is
expressed from a plurality of separate bags at approximately
the same time, this reduction in flow allows the operator to
process a greater number of containers more efficiently.
A principal function of the red cell barrier medium is
to separate a red cell-containing fraction of a biological
fluid from a non-red cell-containing fraction. The red cell
barrier medium may act as an automatic "valve" by slowing or
even stopping the flow of a red cell-containing biological
fluid. In some embodiments, the automatic valve~function may
quickly or instantly stop the flow of the red cell-containing
biological fluid, thereby obviating the need for the operator
to monitor this step.
In one embodiment, a red cell barrier medium suitable
for passing the plasma in about one unit of biological fluid
preferably has, for example, a fiber surface area of about
0.04 to about 3.0 M~/g, and in some embodiments, about 0.06
to about 2.0 MZ/g. One example of a suitable range for the
relative voids volume is about 71~ to about 93~, e.g., about
73~ to about 90~.
One embodiment of a combined leukocyte depletion red
cell barrier medium suitable for passing the plasma in about
one unit of biological fluid preferably has a fiber surface
area of from about 0.3 to about 2.0 Mz/g, e.g., from 0.25 to
about 1.5 MZ/g, or from about 0.35 to about 1.4 Mz/g, e.g.,
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0.4 to 1.2 MZ/g. An exemplary range for the relative voids
volume is about 71% to about 93%, e.g., about 72% to about
91%, or about 75% to about 89%, e.g., 73 to 87%.
These characteristics and ranges may be adjusted or
modified as necessary, e.g., for those embodiments involving
different volumes of biological fluid. Illustratively, the
fiber surface area and/or the voids volume utilized for the _
leukocyte depletion media, the red cell barrier, and the red
cell barrier/leukocyte depletion media as disclosed above may
be adjusted as necessary.
Exemplary leukocyte depletion media, red cell barrier
media and red cell barrier/leukocyte depletion media are
disclosed in, for example, U. S. Patent Nos. 4,880,548,
5,100,564, 5,152,905, 5,443,743, 5,472,621 and 5,670,060.
The second element 2 comprises at least one, and in
some embodiments, no more than one, membrane. Preferably,
the second element comprises a microporous polymeric
membrane. Typically, the second element comprises a
hydrophilic microporous polymeric membrane.
A variety of membranes are suitable for use in
accordance with the invention, and a variety of polymeric
materials are suitable for producing these membranes.
Illustrative suitable membranes include, but are not
limited to, membranes produced from polymeric materials as
described above, e.g., polyamide membranes, such as nylon
membranes (including, but not limited to, nylon 6, 6T, 11,
46, 66, and 610), polysulfone membranes, such as
polyarylsulfone, polysulfone, polyethersulfone, and
polyarylsulfone membranes. Other suitable membranes include
membranes made from, for example, polyacrylates,
polyvinylidene fluoride, polypropylene, cellulose acetate,
and nitrocellulose.
Suitable membranes include, for example, membranes
described in U.S. Patent Nos. 4,340,479, 4,702,840,
4,707,266, 4,900,449, 4,906,374, 4,964,989, 4,964,990,
5,108,607, 5,277,812 and 5,531,893, and International
Publication No. WO 98/21588.
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A variety of commercially available membranes are also
suitable for carrying out the invention. Suitable membranes
include, but are not limited to, those available from Pall
Corporation under the tradenames BIODYNE° PLUS, BIODYNE° A,
BIODYNE° B, BIODYNE° C, POSIDYNE°, LOPRODYNE°
LP, SUPOR°,
SUPOR° 30Q, SUPOR° 30 PLUS, and PREDATOR°.
The membranes and/or polymeric materials can be _
unmodified or modified as described above, e.g., to affect
the CWST, to provide a low affinity for amide
group-containing materials and/or to include a surface'.
charge.
Preferably, the second element has a pore structure that
will substantially prevent the passage therethrough of
undesirable material, e.g., large particulate matter,
microaggregates and/or blood cells. For example, the second
element can sieve out at least level of the undesirable
material passing through the first element. Accordingly, at
least one membrane typically has a pore size of about 5
micrometers or less, e.g., about 0.3 to about 4 micrometers.
In one preferred embodiment, the membrane has a pore size of
about 3 micrometers or less.
As noted earlier, the second element can be treated for
increased efficiency in processing a biological fluid.
Illustratively, in one preferred embodiment, the second
element is surface modified to provide a low affinity for
amide group-containing materials such as proteinaceous
materials, as described in, for example, U.S. Patent Nos.
4,906,374, 5,019,260, 4,886,836,_ and 4,964,989. In some
embodiments, the second element has an adsorption of
proteinaceous material measured by the Bovine Serum Albumin
(BSA) Adsorption Test of less than 100 micrograms per square
centimeter. Illustratively, the second element can have an
adsorption of proteinaceous material measured by the BSA
Adsorption Test of less than about 50 micrograms per square
centimeter, and in some embodiments, about 35 micrograms/cm2,
or less.
The second element can have any suitable thickness. For
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example, in one illustrative embodiment, the second element
has a thickness in the range of from about 0.002 inches to
. about 0.010 inches, preferably about 0.005 inches to about
0.0075 inches.
The filter 10 can include additional elements, layers,
or components, that can have different structures and/or
functions, e.g., at least one of prefiltration, support,
drainage, spacing and cushioning. Illustratively, the filter
can also include at least one additional element such as a
mesh and/or a screen.
The filter, comprising the first and second elements, is
typically placed in a housing 25 to form a filter assembly or
filter device 100. Preferably, the filter device is
sterilizable. Any housing of suitable shape to provide an
inlet and an outlet may be employed. The housing may be
fabricated from any suitably rigid, impervious material,
including any impervious thermoplastic material, which is
compatible with the fluid being processed. The housing may
include an arrangement of one or more channels, grooves,
conduits, passages, ribs, or the like, which may be
serpentine, parallel, curved, circular, or a variety of other
configurations.
Suitable exemplary housings are disclosed in U.S. Patent
Nos. 5,100,564, 5,152;905, 4,923,620, 4,880,548, 4,925,572,
and 5,660,731, as well as International Publication No. WO
91/04088. It is intended that the present invention not be
limited by the type, shape, or construction of the housing.
Typically, the filter device or filter assembly 100
according to the inventiori~is included in a biological fluid
processing system, e.g., a system including a plurality of
conduits and containers, preferably flexible containers such
as blood bags. In one preferred embodiment, a system
according to the invention comprises a closed system
including the filter device.
Figure 2 illustrates an embodiment of a biological fluid
processing system 1000, including the filter device 100, a
plurality of containers 50-53, and a plurality of connectors
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3, wherein the components of the system are in fluid
communication with each other via a plurality of conduits.
In this illustrated embodiment, the system 1000 also includes
a phlebotomy needle 501 (with a cover), a phlebotomy needle
protector 500, a sampling arrangement 600, a sampling ,
arrangement needle or cannula 601 (with a cover), an
additional filter device, leukocyte filter device 200, and a_
plurality of flow control devices 15 {such as one or more
valves, clamps, or the like).
In those embodiments including a sampling arrangement
600, the arrangement is preferably arranged to minimize
contamination of the collected biological fluid by allowing a
first sample of the collected fluid to be passed to a
location other than the collection container 50, e.g., the
first sample is passed from phlebotomy needle 501 through the
sampling arrangement 600 and sampling arrangement needle 601
into a sampling device (not shown) such as an evacuated
stoppered container, e.g., a vacutainer.
One or more containers in the system can be suitable for
holding, for example, blood components and/or additives
(e. g., nutrients, storage solutions, and/or inactivation
agents). The system can include additional components, such
as, for example, additional filter devices, including
leukocyte depletion filter devices, (with and without filter
bypass loops). Additionally, or alternatively, the system
can include at least one of the following: a gas collection
and displacement arrangement (e. g., including a liquid
barrier medium and/or a gas collection and displacement bag,
as disclosed in U.S. Patent No. 5,472,621 and International
Publication No. WO 93/25295), a device for processing a fluid
including gas (e.g., as disclosed in U.S. Patent No.
5,451,321 and International Publication No. WO 91/17809) such
as one or more gas inlets, one or more gas outlets. In some
embodiments, the system includes at least one of the
following: as a sampling arrangement (e.g., as disclosed in
International Publication No. WO 98/28057), one or more
needles and/or cannulas, and a phlebotomy needle protector.
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In the embodiment of the system 1000 illustrated in
Figure 2, the system includes leukocyte filter device 200,
e.g., to reduce the level of leukocytes from a unit of
biological fluid before further processing the fluid, or at
5 least further processing one or more components of the fluid.
For example, in accordance with one embodiment utilizing
the illustrated system, wherein flow control devices 15 are
operated to allow and/or prevent flow as desired, a unit of
biological fluid, e.g., a unit of whole blood, is passed from
10 phlebotomy needle 501 into collection bag 50 and then through
a leukocyte depletion filter device 200 (that may also
deplete platelets from the blood) into first container or
first satellite bag 51. If desired, processing the unit of
whole blood can include passing gas (e.g., air) through at
15 Least one vent upstream and/or downstream of the filter
device 200 and/or passing gas along a gas collection and
displacement loop communicating with the inlet and outlet of
the device 200.
The leukocyte-depleted (or leukocyte- and
platelet-depleted) fluid in first satellite container 51,
that still contains some level of leukocytes (and typically
some level of platelets), is preferably centrifuged to
provide a supernatant layer comprising plasma-rich fluid, and
a sediment layer comprising red blood cells. Subsequently,
the plasma-rich fluid (e. g., platelet-poor plasma) is passed
from first satellite container 51 through the second filter
device 100, i.e., the device comprising a filter 10 having
first and second filter elements 1 and 2 as described above,
to provide plasma-rich fluid substantially free of leukocytes
and without externally visible red blood cells in second
satellite container 52. In an embodiment, the filtered
plasma-rich fluid is substantially free of red blood cells,
leukocytes, and platelets.
The separated blood components can be further processed
if desired. For example, in accordance with the embodiment
of the system illustrated in Figure 2, an additive solution
can be passed from third satellite bag 53 to be combined with
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the red cells in second satellite bag 51, and the red
cells/additive solution can be stored until needed.
EXAMPLE
As generally shown in Figure 1, a filter 10 comprising a ,
first filter element 1 and a second filter element 2 is
placed in a housing having an inlet and an outlet to provide _
the filter device 100, wherein the first filter element 1 is
upstream of the second element 2. Each filter element is a
planar circular disc having a diameter of about 47 mm.
A system is arranged as generally shown in Figure 2,
e.g., the system includes a leukocyte filter device 200, the
filter device 100 as described above, a collection bag 50, as
well as first, second, and third satellite containers 51-53.
The first filter element comprises 8 layers of
melt-blown PBT fibers, surface modified as described in U.S.
Patent No. 5,152,905 using hydroxyethyl methacrylate and
methacrylic acid. The first filter element has a CWST of 95
dynes/cm, and a negative zeta potential at physiological pH.
The filter has no more than one membrane, as the second
filter element is a single nylon 66 membrane, commercially
available from Pall Corporation (East Hills, NY) under the
tradename LOPRODYNE~ LP, having a nominal pore size of 3
micrometers.
A unit of whole blood is collected in a collection bag
50 containing an anticoagulant, and passed through a
leukocyte- and platelet-depleting filter 200 into first
satellite bag 51 The filtered blood, that now has about 1 x
105 leukocytes in the unit, is centrifuged in the satellite
bag 51 to provide a supernatant layer of platelet-poor-plasma
(PPP) and a sediment layer including red blood cells. The
satellite bag is placed in a plasma expressor and the PPP is
expressed from the bag, through the filter device 100 (i.e.,
fluid is passed through the first filter element 1 and then
through the second filter element 2), and into an empty
second satellite bag 52. Flow stops after the "front" of red
cells from the sediment layer contacts the filter, and there
CA 02345535 2001-03-29
WO 00/20053 PCT/US99/22478
17
are no red cells in the fluid downstream of the filter
visible to the technician operating the system.
Analysis of the unit of filtered PPP shows 55 white
blood cells in the total volume of PPP. There are less than
about 21 platelets/~L present.
This example shows that filter devices according to the
invention can provide substantially cell-free plasma. _
All of the references cited herein, including
publications, patents, and patent applications, are hereby
incorporated in their entireties by reference.
While the invention has been described in some detail by
way of illustration and example, it should be understood that
the invention is susceptible to various modifications and
alternative forms, and is not restricted to the specific
embodiments set forth. It should be understood that these
specific embodiments are not intended to limit the invention
but, on the contrary, the intention is to cover all
modifications, equivalents, and alternatives falling within
the spirit and scope of the invention.
