JP2002526172A - Biological fluid filters and systems - Google Patents

Abstract

(57) Abstract A filter for producing a plasma-rich fluid substantially free of leukocytes is disclosed.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[Related application]

This application claims priority of US Provisional Patent Application 60 / 102,973, filed October 2, 1998, the contents of which application is incorporated by reference.

[0002]

【Technical field】

The present invention relates to filters for treating biological fluids, and more particularly to filters for providing biological fluids with reduced white blood cells. Preferably, the filter provides a biological fluid that is substantially free of blood cells (blood cells, ie, white blood cells, red blood cells, platelets).

[0003]

BACKGROUND OF THE INVENTION

Blood contains many components including plasma, platelets, red blood cells, and various white blood cells. Blood components can be separated and further processed for a variety of uses, particularly as blood transfusion (infusion) preparations. By way of example, red blood cells (typically enriched as concentrated red blood cells), plasma, and platelets (typically enriched as concentrated platelets) can be administered separately to different patients. Some components, such as plasma and / or platelets, can be pooled prior to administration. Also, the plasma can be further processed, eg, fractionated, to provide enriched components for a variety of uses.

[0004] Unfortunately, there are certain substances that are not desirable to be present in transfusion preparations.
For example, while leukocytes fight infection and engulf and digest invading microorganisms and foreign bodies, the presence of leukocytes in a transfusion formulation may be undesirable. Because, for example,
Leukocytes can cause side effects (eg, a febrile reaction) in transfused patients. Also, blood transfusion products containing platelets and blood transfusion products rich in plasma should be substantially free of red blood cells. The reason is that the presence of substantial levels of red blood cells in a transfusion product (especially if the transfusion product is pooled) can produce an adverse immune response in the patient.

[0005] However, some commercial filters have many disadvantages. For example, certain filters may not be able to remove the desired level and / or type of material, or may have an undesirably large holding volume, or may increase processing time. Alternatively or additionally, the use of certain filters requires labor and / or time consuming work.

Accordingly, filters for use with biological fluids such as blood and blood components, and in particular, to produce plasma-rich blood products with minimal contamination of plasma-rich blood products by white and red blood cells There is a need in the art for a filter to perform this. The above and other advantages of the present invention will be apparent from the following description.

[0007]

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided a filter device for providing a plasma-rich biological fluid substantially free of leukocytes, the filter device comprising a first filter element and a second filter element. Wherein the first filter element comprises a porous fibrous leukocyte reduction medium and the second filter element disposed downstream of the first filter element comprises a porous membrane. Methods using the filter device, as well as systems including the filter device, are also provided.

[0008]

DETAILED DESCRIPTION OF THE INVENTION

According to one aspect of the invention, a filter device for treating a biological fluid comprises:
A housing having an inlet and an outlet, forming a fluid flow path between the inlet and the outlet, and a filter disposed in the housing across the fluid flow path, the filter having a CWST of at least about A first filter element comprising a 70 dynes / cm porous fibrous leukocyte reduction medium and a second filter element comprising a porous membrane disposed downstream of the first filter element and having a pore size of about 5 μm or less. , And where
The filter is tuned to allow the passage of plasma and substantially impede the passage of white blood cells.

In another aspect, a filter device for treating a biological fluid has a housing having an inlet and an outlet, forming a fluid flow path between the inlet and the outlet, and traversing the fluid flow path. A filter disposed in the housing, the filter comprising a first filter element comprising a porous fibrous red blood cell barrier having a CWST of at least about 70 dynes / cm and a white blood cell reducing medium. A second filter element, comprising a porous membrane having a pore size of about 5 μm or less, disposed downstream of the filter element;
Wherein the filter is tuned to pass plasma and substantially block the passage of white blood cells.

[0010] In one preferred embodiment, the filter is tuned to provide a fluid containing plasma substantially free of blood cells. A method for treating a biological fluid according to one embodiment of the present invention includes passing a plasma-enriched biological fluid containing leukocytes through a filter device including a filter including a fibrous leukocyte reduction medium and a membrane. And filtered, substantially free of leukocytes,
Collecting the plasma-rich biological fluid.

According to another aspect of the present invention, a method of treating a biological fluid comprises: providing a filter device comprising a filter comprising a fibrous red blood cell barrier medium and a membrane;
Passing the plasma-rich biological fluid and collecting the filtered, substantially leukocyte-free, plasma-rich biological fluid.

A method for treating a biological fluid provided by another aspect of the present invention provides a supernatant layer containing a plasma-rich fluid containing white blood cells and a sedimentation layer containing a fluid containing red blood cells. Treating the biological fluid as described above, passing the plasma-rich fluid containing leukocytes through a filter device comprising a filter comprising a fibrous leukocyte reduction medium and a membrane, and filtering, substantially filtering. Includes collecting plasma-rich fluids that do not contain leukocytes.

[0013] One preferred embodiment of the method according to the invention involves treating a biological fluid to provide a fluid containing plasma, which is substantially free of blood cells. A system according to one aspect of the invention includes a filter device interposed in fluid communication with at least two containers, such as a plastic blood bag. In one preferred embodiment, the system includes a closure system.

As used herein, biological fluids include all treated or untreated fluids associated with the organism, especially 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 solutions and / or anticoagulant solutions; platelet-rich (PC), platelet-rich plasma (PRP), platelet poor plasma
(PPP), platelet-free plasma, plasma, components obtained from plasma, concentrated red blood cells (PRC),
Blood components such as transition zone material or buffy coat (BC); blood products derived from blood or blood components or from bone marrow; red blood cells separated from plasma and resuspended in a physiological or antifreeze fluid And platelets separated from plasma and resuspended in a physiological or antifreeze fluid. The biological fluid may have been processed to remove some of the white blood cells prior to processing according to the present invention. As used herein, a blood product or biological fluid refers to the aforementioned components, as well as similar blood products or biological fluids having similar properties and obtained by other means.

“Unit” is the amount of biological fluid obtained from one donor or one unit of whole blood. This may also mean the amount collected during a single donation. The volume of one unit varies, and the volume typically varies from donor to donor. For some blood components, especially platelets and buffy coats, multiple units may be pooled or combined, typically by combining four or more units.

The term “closed” system as used herein refers to the collection and processing of biological fluids, such as blood donations, blood specimens, and / or blood components (and, if desired, manipulation, eg, separation of parts, Means a system that allows the separation (filtration, storage, and preservation of components) without having to compromise with the integrity of the system (ie, without compromising this integrity). The closure system may have been achieved from the outset, or it may result from connecting the system components using what is known as a "sterile docking" device. An example of a sterile docking device is described in U.S. Pat.
Nos. 4,507,119, 4,737,214 and 4,913,756.

Each element of the device of the present invention is described in more detail below. In the following description, similar elements have similar reference numerals. FIG. 1 shows one embodiment of a filter device 100 having an inlet 20 and an outlet 30 and a housing 25 defining a fluid flow path between the inlet and the outlet. A filter 10 having a first filter element 1 and a second filter element 2 is arranged in the housing across the fluid flow path.

According to the present invention, the filter 10 is designed to remove a desired amount of leukocytes. Typically, the filter will comprise at least about 90%, preferably at least about 99%, even more preferably at least about 99.9% of white blood cells from plasma-rich fluid passing through the filter.
It is designed to eliminate the above. For example, the filter can be designed to provide a filtered fluid having a white blood cell count of about 1 × 10 ⁴ or less (the filtered fluid). In some embodiments, the filter can be designed to provide a filtered fluid having a white blood cell count of about 1 × 10 ³ or less.

In one embodiment, the fluid to be filtered comprises platelet poor plasma and the resulting filtered fluid has a white blood cell count of about 200 cells / liter or less, preferably about 100 cells / liter or less. In some embodiments, the filtered fluid has a white blood cell count of about 75 / unit (eg, one unit is about 300 ml).
Volume).

Preferably, the filter is designed to block the passage of significant levels of red blood cells, and may also be designed to block the passage of a substantial number of platelets. In one preferred embodiment, there is no visible sign of red blood cells downstream (to the technician performing the filtration) downstream of the filter. For example, there should be no visible signs of red blood cells in the tube leading from the outlet of the filter device to the downstream vessel. Typically, the filtration fluid (e.g., the fluid in the vessel downstream of the filter)
Contains less than about 5000 platelets / μL. In a representative embodiment, the unit of filtration fluid obtained has a platelet count of about 1 × 10 ⁹ or less. In one preferred embodiment, the unit of filtration fluid obtained has a platelet count of about 1 × 10 ⁴ or less.

The filter is designed to filter a suitable volume of fluid in a suitable time. For example, the filter may be capable of filtering about 200 to about 400 ml of fluid with minimal effect on overall processing time. By way of example, in some embodiments, the filter can filter about 250 to about 350 ml of the fluid within about 15 minutes, for example, about 10 minutes.

In some embodiments, the filter can filter from about 500 to about 1000 ml of the fluid in about 25 minutes or less, preferably in about 20 minutes or less. In one embodiment, the filter is about
600 to about 850 ml of fluid (eg, 1 unit of apheresis <component donated> plasma)
Can be filtered within about 18 minutes.

Preferably, the first (filter) element 1 of the filter 10 (which comprises a depth filter) comprises a leukocyte reduction medium or a medium which combines leukocyte reduction and a red blood cell barrier, wherein Is at least partially removed by adsorption. In some aspects, the first element 1 also removes at least some of the white blood cells by filtration.

The second (filter) element 2 of the filter 10, typically with a membrane, more preferably a microporous membrane, substantially blocks the passage of blood cells, eg, white blood cells and / or red blood cells. Has pore size.

The production of the porous media of the first and second filter elements according to the present invention, ie, the leukocyte reduction medium, the erythrocyte barrier medium, the medium that combines the leukocyte reduction and the erythrocyte barrier, and the membrane, requires a synthetic high A variety of materials can be used, including polymeric materials. Suitable synthetic polymer 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.

A first element 1 comprising at least one of a leukocyte reduction medium, an erythrocyte barrier medium and a medium that combines leukocyte reduction and erythrocyte barrier is described, for example, in US Pat.
No. 548; No. 4,925,572; No. 5,152,905; No. 5,443,743; No. 5,472,621;
No. 5,582,907; and 5,670,060; fibrous media;
It includes porous fibrous media, preferably made of synthetic polymers, typically media made from meltblown fibers. The element may include a preform,
Multiple layers and / or media can be provided.

The first component 1 and / or the second component 2 can be treated to increase the efficiency of treating biological fluids. For example, the first element and / or the second element may be subjected to a surface modification to change the critical wet surface tension (CWST), for example, as described in the aforementioned US patent.

Preferably, the first element 1 according to an embodiment of the present invention, for example, a leukocyte reduction medium, an erythrocyte barrier medium, or a medium that combines leukocyte reduction and erythrocyte barrier is CWST
Is about 70 dynes / cm or more, and more preferably, the CWST is about 72 dynes / cm or more.
For example, the CWST for this medium is in the range of about 75 to about 115 dynes / cm, for example, about
It may be in the range of 80 to about 100 dynes / cm. In some aspects, the medium has a CWST of about 85
Dynes / cm or more, for example, in the range of about 90 to about 105 dynes / cm, or about 85 to about 98
It is in the range of dynes / cm.

The surface properties of the first element and / or the second element can be modified by chemical reactions including, for example, wet or dry oxidation, by coating or depositing a polymer on the surface, or by a grafting reaction. Yes (e.g., to alter CWST, to provide low affinity for amide group-containing materials, surface charge,
For example, to impart a positive or negative charge and / or to change the polarity or hydrophilicity of the surface). Modifications include, for example, irradiation, coating and / or curing of polar or charged monomers, charged polymers on the surface, and performing chemical reactions to attach functional groups to the surface. The grafting reaction is performed by gas plasma, heat, Van de Graaff generator, ultraviolet light, electron beam,
Alternatively, it may be activated by exposure to an energy source such as various forms of radiation, or by surface etching or deposition using a plasma treatment. In some aspects, the first and / or second filter elements can be modified, for example, as described in the aforementioned US patents.

Typically, the first component 1 has a negative zeta potential (eg, within a range of about −3 to about −30 millivolts) at physiological pH (eg, a pH of about 7 to about 7.4). About -7 to
(In the range of about -20 millivolts).

According to the invention, the first element 1 can be designed to remove a desired amount of leukocytes. Typically, the first element is designed to remove about 90% or more, preferably about 99% or more, or about 99.9% or more of white blood cells from the fluid passing through the filter.

One embodiment of a leukocyte reduction medium suitable for passing plasma in approximately one unit of a biological fluid (eg, passing a plasma-rich fluid such as platelet poor plasma) includes, for example, a fiber surface area in the range of about 0.08 to about 1.4 M ² / g, in some embodiments in the range of from about 0.1 to about 0.9 M ² / g. One embodiment of a representative range for relative voids volume is from about 50% to about 92%, for example, from about 60% to about 89%.

In some embodiments, the first filter element comprises a red blood cell barrier medium, both a red blood cell barrier medium and a white blood cell reduction medium, or more preferably, a medium that combines the red blood cell barrier and white blood cell reduction. The erythrocyte barrier medium according to the present invention comprises a porous medium that allows the separation of a erythrocyte-free biological fluid, such as plasma or a platelet and plasma suspension, from a erythrocyte-containing biological fluid. In. The red blood cell barrier medium prevents biological fluids containing significant levels of red blood cells from flowing into a container, such as an associated bag or receiving container, located downstream of the barrier medium. The erythrocyte barrier medium is capable of passing fluids that do not contain erythrocytes, but as soon as the erythrocyte-containing fluid approaches this barrier medium, it significantly slows or effectively stops the flow of biological fluids. Let it. For example, an erythrocyte barrier medium may allow the passage of plasma-rich fluids, but when erythrocytes block the medium, the flow is suddenly stopped.

By slowing the flow of the biological fluid, the erythrocyte barrier medium allows the operator to manually stop the flow, so that, for example, significant levels of erythrocytes pass through the barrier medium Biological fluid, including red blood cells, can be prevented from flowing into a container, such as an associated bag or receiving container, located downstream of the barrier medium. This aspect of the invention gives the operator more time to intervene and stop the flow. For example, when the supernatant plasma-rich fluid can flow through the erythrocyte barrier medium at an initial flow rate of about 15 ml / min, the fluid containing sedimented erythrocytes approaches the medium as soon as it approaches the medium. Drops to about 5 ml / min.
For example, a 33% reduction in flow rate can give the operator sufficient time to stop the flow at the appropriate time. In some situations, for example, plasma-rich fluid may be squeezed out of multiple satellite bags at about the same time, in which case this reduced flow rate would allow the operator to process more containers more efficiently. It becomes possible.

The primary function of the red blood cell barrier medium is to separate the red blood cell-containing fraction of the biological fluid from the red blood cell-free fraction. The red blood cell barrier medium can act as an automatic "valve" by slowing or even stopping the flow of a biological fluid containing red blood cells. In some aspects, the automatic valve function can stop the flow of a biological fluid containing red blood cells quickly or instantly,
This eliminates the need for the operator to monitor this process.

In one embodiment, an erythrocyte barrier medium suitable for passing plasma in about 1 unit of biological fluid has a fiber surface area of, for example, from about 0.04 to about 3.0 M ² / g, in some embodiments. at about 0.06 to about ² M 2 / g. One example of a suitable range for the relative porosity is from about 71% to about 93%.
For example, from about 73% to about 90%.

One embodiment of a medium that combines leukocyte reduction and erythrocyte barrier, suitable for passing plasma in about one unit of biological fluid, preferably has a fiber surface area of about 0.3 to about 2.0.
M ² / g, for example, in the range of about 0.25 to about 1.5 M ² / g within or about 0.35 to about 1.4 M ² / g, for example, in the range of 0.4 ~1.2 M ² / g. A typical range of relative porosity ranges is from about 71% to about 93%, for example, about 72% to about 91%, or about 75% to about 89%, for example, 73%.
% To 87%.

These properties and ranges may be adjusted or varied as needed, for example, for embodiments with different amounts of biological fluid. For example, the fiber surface area and / or porosity utilized for the leukocyte reduction media, erythrocyte barrier media, and erythrocyte barrier / leukocyte reduction media as disclosed above can be adjusted as needed.

Examples of leukocyte reduction media, erythrocyte barrier media, and erythrocyte barrier / leukocyte reduction media are described in US Pat. Nos. 4,880,548, 5,100,564, 5,152,905, 5,
Nos. 443,743, 5,472,621 and 5,670,060.

The second filter element 2 comprises at least one, and in some embodiments no more than one, membrane. Preferably, the second element comprises a microporous polymer membrane. Typically, the second element comprises a hydrophilic microporous polymer membrane.

A variety of membranes are suitable for use according to the present invention, and a variety of polymeric materials are suitable for making these membranes. Examples of suitable membranes include, but are not limited to, membranes made from polymer materials as described above, for example, nylon membranes (including but not limited to nylon 6, nylon 6,
And polysulfone membranes such as polyarylsulfones, polysulfones, polyethersulfones and polyarylsulfone membranes (including 6T, 11, 46, 66 and 610). Other suitable membranes include, for example, membranes made from polyacrylate, polyvinylidene fluoride, polypropylene, cellulose acetate, and nitrocellulose.

Suitable membranes include, for example, US Pat. Nos. 4,340,479; 4,702,840;
707,266, 4,900,449, 4,906,374, 4,964,989, 4,964,990
Nos. 5,108,607, 5,277,812 and 5,531,893, and international publication
No. WO 98/21588.

A variety of commercially available membranes are also suitable for practicing the present invention. Suitable membranes include:
Without limitation, Pall Corporation provides BIODYNE ^™ PLUS, BIODYNE ^™ A
, BIODYNE ^™ B, BIODYNE ^™ C, POSIDYNE ^™ , LOPRODYNE ^™ LP, SUPOR ^™ , SUPOR ^™ 30Q, SUPOR ^™ 30 PLUS, and PREDATOR ^™ .

The membrane and / or polymer material may be unmodified, or, as described above,
For example, it can be modified to alter the CWST, to provide a lower affinity for the amide group containing material, and / or to provide a surface charge.

Preferably, the second element has a pore structure that substantially impedes the passage of undesired substances, such as large particulate matter, microaggregates, and / or blood cells. For example, the second element can screen at least some level of unwanted material that has passed through the first element. Therefore, at least one
One membrane typically has a pore size of about 5 μm or less, for example, about 0.3-4 μm. In one preferred embodiment, the pore size of the membrane is no more than about 3 μm.

As mentioned above, the second component can be processed to increase the efficiency of processing the biological fluid. By way of example, in one preferred embodiment, the second element is an amide group-containing material such as a protein-based material, for example, as described in U.S. Patent Nos. 4,906,374, 5,019,260, 4,886,836 and 4,964,989. Surface modified to give low affinity to it. In some embodiments, the second factor is an amount of proteinaceous substance adsorbed as measured by a bovine serum albumin (BSA) adsorption test,
Less than 100 μg / cm ² . By way of example, the second element may have a protein-based material adsorption of less than about 50 μg / cm ² , and in some embodiments less than about 35 μg / cm ^2, as measured by the BSA adsorption test.

The thickness of the second element may be any suitable thickness. For example, in one exemplary embodiment, the thickness of the second element ranges from about 0.002 to about 0.010 inches (about 0.05 to about 0.25 mm), and preferably ranges from about 0.005 to about 0.0075 inches (about 0.13 to about 0.19 mm). Is within.

The filter 10 may comprise additional elements, layers or components, which may have different structures and / or functions, such as at least one of pre-filtration means, support means, drainage means, spacing means, and cushion means , Can be provided. By way of example, the filter may comprise at least one additional element, such as a mesh and / or a screen.

The filter 10 comprising the first and second elements is typically housed in a housing 25 to form a filter assembly or device 100. Preferably, the filter device is sterilizable. Any suitably shaped housing that provides an inlet and an outlet can be employed. The housing can be made from any suitably rigid and impermeable material, including an impermeable thermoplastic material that is compatible with the fluid being treated. The housing may include an arrangement of one or more channels, grooves, conduits, passages, ribs, etc., which may take a meandering, parallel, curved, circular, or other variety.

Examples of suitable housings are described in US Pat. Nos. 5,100,564, 5,152,905, 4,923,62.
Nos. 0, 4,880,548, 4,925,572 and 5,660,731, and International Publication No. WO 91/04088. The invention is not limited by the type, shape or structure of the housing.

Typically, a filter device or filter assembly 100 according to the present invention is a biological fluid treatment system, for example, a system comprising a plurality of conduits and containers, preferably a flexible container such as a blood bag. Is provided. In one preferred embodiment, the system according to the invention comprises a closing system comprising the filter device.

FIG. 2 shows a filter device 100, a plurality of containers 50 to 53, and a plurality of connectors 3.
1 illustrates an embodiment of a biological fluid treatment system 1000 comprising: These components (devices, vessels) of the system are in fluid communication with each other by a plurality of conduits. In this illustrated embodiment, the system 1000 includes a phlebotomy needle 501 (with cover), a phlebotomy needle protector 500, a sampling facility 600, a sampling facility needle or cannula 601 (with a cover), and an additional filter device, a leukocyte filter device. 200,
And a plurality of flow control devices 15 (one or more valves, clamps, etc.).

In embodiments with a sampling facility 600, the facility minimizes contamination of the collected fluid by sending a first sample of the collected biological fluid to another location other than the collection bag 50. It is preferable to arrange them so as to limit them. For example, a first sample of fluid is delivered from a phlebotomy needle 501 through a sampling facility 600 and a sampling facility needle 601 to a sampling device (not shown), such as a vacuum-sealed container (eg, a vacutainer).

One or more containers in the system may be suitable for containing, for example, blood components and / or additives (eg, nutrient solutions, storage solutions, and / or inactivating agents). Can be. This system is, for example, a leukocyte reduction filter device (
(It may or may not have a filter bypass loop)
Additional elements or components may be provided, such as additional filter devices.
Additionally or alternatively, the system may include at least one of the following: a gas collection and displacement facility (eg, as disclosed in US Pat. No. 5,472,621 and International Publication No. WO 93/25295). Devices for treating gas-containing fluids, such as liquid barrier media and / or gas collection and displacement bags, such as, one or more gas inlets, one or more gas outlets (eg, As disclosed in U.S. Pat. No. 5,451,321 and International Publication No. WO 91/17809). In some aspects, the system comprises at least one of the following:
One or more needles and / or cannulas as sampling equipment (eg, as disclosed in International Publication No. WO 98/28057);
As well as a phlebotomy needle protector.

In the embodiment of the system 1000 shown in FIG. 2, the system includes an additional leukocyte filter device 200. This is to reduce leukocyte levels, for example, from a unit of biological fluid before further processing this fluid, or at least one or more components of the fluid. .

For example, according to one embodiment utilizing the illustrated system for operating the flow control device 15 to flow and / or close a flow as desired, one unit of a biological fluid, eg, one unit of a biological fluid Whole blood is sent from the phlebotomy needle 501 to the collection (blood collection) bag 50 and then through the leukocyte reduction filter device 200 (which may also reduce platelets from the blood) to the first container or first associated container. Sent to bag 51. Optionally, the processing of one unit of whole blood can include flowing gas (eg, air) to at least one vent upstream and / or downstream of the filter device 200 and / or inlet and outlet of the device 200. Flowing gas along a gas collection and purge loop in communication with the gas.

The fluid with reduced white blood cells (or reduced white blood cells and platelets) in the first satellite container 51 still contains some levels of white blood cells (and typically some levels of platelets). The fluid in the container 51 is preferably centrifuged to obtain a supernatant layer containing a plasma-rich fluid and a sedimentation layer containing red blood cells. Thereafter, a plasma-rich fluid (eg, platelet poor plasma) is passed from the first associated container 51 to the second filter device 100,
That is, when pumped through a filter device comprising a filter 10 having first and second filter elements 1 and 2 as described above, it is substantially free of leukocytes and is rich in plasma without red blood cells visible from the outside. Fluid is obtained in the second satellite container 52. In one aspect, the filtered plasma-rich fluid is substantially free of red blood cells, white blood cells, and platelets.

[0058] The separated blood components can be further processed if desired. For example, FIG.
According to the embodiment of the system shown in FIG. 3, the additive solution can be pumped out of the third satellite bag 53 for mixing with the red blood cells in the first satellite bag 51 and the resulting red blood cells /
The additive solution can be stored until needed.

[0059]

【Example】

As shown schematically in FIG. 1, a filter 10 having a first filter element 1 and a second filter element 2 is placed in a housing having an inlet and an outlet to form a filter device 100. Here, the first filter element 1 is upstream of the second filter element 2. Each filter element is a flat disk with a diameter of about 47 mm.

The system is arranged as shown schematically in FIG. For example, the system includes a leukocyte filter device 200, a filter device 100 as described above, a collection bag 50, and first, second and third associated containers 51-53.

[0061] The first filter element is composed of eight layers of meltblown PBT fibers surface modified with hydroxyethyl methacrylate and methacrylic acid as described in US Patent No. 5,152,905. The CWST of this first filter element is
95 dynes / cm and has a negative zeta potential at physiological pH. There is only one membrane in the filter because the second filter element is a single (single) nylon 66 membrane. The nylon 66 membrane is commercially available from Pall Corporation (East Hills, NY, USA) under the trade name LOPRODYNE ^™ LP and has a pore size of 3 μm.

One unit of whole blood is collected in a blood collection bag 50 containing an anticoagulant and sent to a first auxiliary bag 51 via a leukocyte and platelet reduction filter 200. The filtered blood having a white blood cell count of about 1 × 10 ^{5 in the} unit is centrifuged in the accompanying bag 51 to form a supernatant layer of platelet poor plasma (PPP) and a sedimentation layer containing erythrocytes. And separated into The associated bag is set in the plasma extruder and the PPP is extruded from the bag and passed through the filter device 100 (ie, the fluid passes through the first filter element 1 and then through the second filter element) and passes through the empty second associated bag. Send to 52. When the "front" of red blood cells from the sedimentation layer contacts the filter, flow stops and the fluid downstream of the filter has no red blood cells visible to the technician operating the system.

Analysis of units of filtered PPP indicates that the white blood cell count in the total PPP is 55. The number of platelets present is less than about 21 / μL. This example shows that the filter device according to the present invention can provide plasma substantially free of blood cells.

All documents cited herein, including publications, patents and patent applications, are hereby incorporated by reference in their entirety. While the invention has been described in some detail by way of illustration and example, it is understood that the invention is capable of various modifications and changes and is not limited to the specific embodiments described above. Let's do it. These embodiments are not intended to limit the invention, but rather, the invention includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.

[Brief description of the drawings]

FIG. 1 shows one 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.

FIG. 2 shows one embodiment of a system including a filter device according to the present invention.

[Explanation of symbols]

1: First filter element, 2: Second filter element, 3: 10: Filter,
15 :, 20: inlet, 25: housing, 30: outlet, 50: collection (blood collection) bag, 51: first accompanying bag, 52: second accompanying bag, 53: third accompanying bag, 100: filter of the present invention Device, 200: filter device, 500: phlebotomy needle protector, 501: phlebotomy needle, 600: sampling device, 601: needle or cannula for sampling device, 1000: biological fluid treatment system

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) B01D 39/04 B01D 39/04 61/14 500 61/14 500 // A61K 35/14 A61K 35/14 B 35/16 35/16 (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE) , OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL) , SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AL, AM, AT, AU, AZ, BA, BB, BG, B , BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU , SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW (72) Inventor Selman, Byron United States of America, New York State 11743, Huntington, Abbott Drive 89 F term (reference) 4C077 AA12 BB02 KK13 LL13 LL17 LL22 MM07 MM08 NN02 PP04 PP08 PP12 PP13 PP15 4C087 AA01 AA04 BB35 DA16 NA07 ZA51 4D006 GA07 KB14 MA03 MC22 MC31 MC31 MC42 MC18 PB09 PB43 4D019 AA03 B A12 BA13 BB13 BC03 BC13 CB04 CB06

Claims (16)

[Claims] 1. A filter device comprising: a housing having an inlet and an outlet, forming a fluid flow path between the inlet and the outlet; and a filter disposed in the housing across the fluid flow path. A first filter element comprising a porous fibrous leukocyte reduction medium having a CWST of at least about 70 dynes / cm; and a pore having a pore size of about 5 μm or less disposed downstream of the first filter element. A filter element for treating a biological fluid, wherein the filter is adapted to pass plasma and substantially impede the passage of leukocytes. apparatus. 2. A filter device comprising: a housing having an inlet and an outlet, forming a fluid flow path between the inlet and the outlet; and a filter disposed in the housing across the fluid flow path. A first filter element comprising a porous fibrous erythrocyte barrier and a leukocyte reduction medium having a CWST of at least about 70 dynes / cm; and a pore disposed downstream of the first filter element. A second filter element comprising a porous membrane having a size of about 5 μm or less, wherein the filter is tuned to pass plasma and substantially impede the passage of white blood cells. Filter device for treating fluid. 3. The method of claim 1, wherein the first filter element comprises a red blood cell barrier medium.
The described device. 4. An apparatus according to any preceding claim, wherein the first filter element comprises a melt blown fiber. 5. The device according to any of the preceding claims, wherein the first filter element comprises at least two layers. 6. The first filter element having a CWST of at least about 90 dynes /
The device according to any of the preceding claims, wherein the device is cm. 7. The device according to claim 1, wherein the filter has one or less membranes. 8. The device according to any of the preceding claims, wherein the filter is adjusted to substantially impede the passage of red blood cells. 9. A biological fluid treatment system comprising an apparatus according to claim 1 and at least a first container and a second container, both suitable for use with biological fluids. Wherein the apparatus is disposed between a first container and a second container. 10. A method for treating a biological fluid comprising the steps of: passing a plasma-rich biological fluid containing leukocytes through a filter device provided with a filter comprising a fibrous leukocyte reduction medium and a membrane. And collecting the filtered, substantially leukocyte-free, plasma-rich biological fluid. 11. A method for treating a biological fluid comprising the steps of: passing a plasma-rich biological fluid containing leukocytes through a filter device provided with a filter comprising a fibrous erythrocyte barrier medium and a membrane. And collecting the filtered, substantially leukocyte-free, plasma-rich biological fluid. 12. A method for treating a biological fluid comprising the steps of: providing a supernatant layer containing a plasma-rich fluid containing leukocytes and a sedimentation layer containing a fluid containing erythrocytes. Treating the fluid; passing a plasma-rich fluid containing leukocytes through a filter device with a filter comprising a fibrous leukocyte reduction medium and a membrane; and containing filtered, substantially red blood cells and white blood cells. Do not collect fluids rich in plasma. 13. The method of any preceding claim, wherein the plasma-rich fluid containing leukocytes comprises a leukocyte- and platelet-reduced biological fluid. 14. A method for treating a biological fluid comprising the steps of: reducing a white blood cell and a platelet from a biological fluid containing a red blood cell to reduce a white blood cell and a platelet; Treating a biological fluid containing red blood cells, which has reduced white blood cells and platelets, to give a supernatant layer containing plasma and a sedimentation layer containing red blood cells; and filtering the supernatant layer. Through the device, wherein the filter device further reduces leukocytes from the supernatant layer and substantially impedes the passage of red blood cells; and the vessel downstream of the filter device is enriched in plasma substantially free of red blood cells and white blood cells. Collect fluid. 15. A method comprising passing a biological fluid through a filter device according to any one of claims 1 to 8 and collecting the filtered substantially blood cell-free biological fluid. , A method of producing a biological fluid substantially free of blood cells. 16. The method of claim 17, wherein collecting the filtered plasma-rich biological fluid comprises passing the plasma-rich biological fluid containing white blood cells through a filter device and substantially free of red blood cells and white blood cells. A method according to any preceding claim, comprising collecting the enriched plasma-rich biological fluid.