EP1123123A1 - System und filter für biologische flüssigkeiten - Google Patents
System und filter für biologische flüssigkeitenInfo
- Publication number
- EP1123123A1 EP1123123A1 EP99948497A EP99948497A EP1123123A1 EP 1123123 A1 EP1123123 A1 EP 1123123A1 EP 99948497 A EP99948497 A EP 99948497A EP 99948497 A EP99948497 A EP 99948497A EP 1123123 A1 EP1123123 A1 EP 1123123A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- filter
- biological fluid
- fluid
- plasma
- rich
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000013060 biological fluid Substances 0.000 title claims description 67
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 82
- 239000012530 fluid Substances 0.000 claims abstract description 65
- 210000004027 cell Anatomy 0.000 claims description 45
- 239000012528 membrane Substances 0.000 claims description 36
- 230000004888 barrier function Effects 0.000 claims description 34
- 210000003743 erythrocyte Anatomy 0.000 claims description 28
- 238000012545 processing Methods 0.000 claims description 28
- 210000004369 blood Anatomy 0.000 claims description 21
- 239000008280 blood Substances 0.000 claims description 21
- 210000001772 blood platelet Anatomy 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 12
- 239000011148 porous material Substances 0.000 claims description 9
- 239000006228 supernatant Substances 0.000 claims description 8
- 239000000835 fiber Substances 0.000 claims description 7
- 239000013049 sediment Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000000779 depleting effect Effects 0.000 claims 1
- 210000002381 plasma Anatomy 0.000 description 44
- 239000000463 material Substances 0.000 description 18
- 239000000306 component Substances 0.000 description 13
- 239000012503 blood component Substances 0.000 description 8
- -1 e.g. Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000005070 sampling Methods 0.000 description 7
- 239000010836 blood and blood product Substances 0.000 description 5
- 229940125691 blood product Drugs 0.000 description 5
- 230000012953 feeding on blood of other organism Effects 0.000 description 5
- 238000001179 sorption measurement Methods 0.000 description 5
- 229920002302 Nylon 6,6 Polymers 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 229920002492 poly(sulfone) Polymers 0.000 description 3
- 229920001707 polybutylene terephthalate Polymers 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000003634 thrombocyte concentrate Substances 0.000 description 3
- 229920000571 Nylon 11 Polymers 0.000 description 2
- 229920002292 Nylon 6 Polymers 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 239000004695 Polyether sulfone Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 230000000959 cryoprotective effect Effects 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000003032 molecular docking Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 229920006111 poly(hexamethylene terephthalamide) Polymers 0.000 description 2
- 229920006393 polyether sulfone Polymers 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 230000001012 protector Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241001631457 Cannula Species 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229920003189 Nylon 4,6 Polymers 0.000 description 1
- 229920000305 Nylon 6,10 Polymers 0.000 description 1
- 229920000572 Nylon 6/12 Polymers 0.000 description 1
- 229920000393 Nylon 6/6T Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000306 polymethylpentene Polymers 0.000 description 1
- 239000011116 polymethylpentene Substances 0.000 description 1
- 244000062645 predators Species 0.000 description 1
- 238000011045 prefiltration Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012815 thermoplastic material Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/12—Composite membranes; Ultra-thin membranes
- B01D69/1218—Layers having the same chemical composition, but different properties, e.g. pore size, molecular weight or porosity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/02—Blood transfusion apparatus
- A61M1/0209—Multiple bag systems for separating or storing blood components
- A61M1/0218—Multiple bag systems for separating or storing blood components with filters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3627—Degassing devices; Buffer reservoirs; Drip chambers; Blood filters
- A61M1/3633—Blood component filters, e.g. leukocyte filters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/14—Ultrafiltration; Microfiltration
- B01D61/18—Apparatus therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/02—Blood transfusion apparatus
- A61M1/0209—Multiple bag systems for separating or storing blood components
- A61M1/0218—Multiple bag systems for separating or storing blood components with filters
- A61M1/0222—Multiple bag systems for separating or storing blood components with filters and filter bypass
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/02—Blood transfusion apparatus
- A61M1/0209—Multiple bag systems for separating or storing blood components
- A61M1/0231—Multiple bag systems for separating or storing blood components with gas separating means, e.g. air outlet through microporous membrane or gas bag
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0427—Platelets; Thrombocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/04—Liquids
- A61M2202/0413—Blood
- A61M2202/0439—White blood cells; Leucocytes
Definitions
- This invention relates to a filter for processing a biological fluid, more particularly, a filter that provides a leukocyte-depleted biological fluid.
- the filter provides a biological fluid that is substantially free of blood cells.
- 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.
- transfusion product some material is undesirably present in transfusion product.
- 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.
- 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 have been pooled) can lead to an adverse immune response by the patient .
- 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.
- 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.
- 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.
- 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.
- the filter is arranged to provide a substantially cell-free plasma-containing fluid.
- a method for processing a biological fluid 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.
- a method for processing a biological fluid comprises passing 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 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 comprises a filter device, interposed between, and in fluid communication with, at least two containers such as plastic blood bags.
- the system comprises a closed system.
- 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 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.
- blood product or biological fluid refers
- 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 .
- 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.
- sterile docking devices are disclosed in U.S. Patent Nos . 4,507,119, 4,737,214, and 4,913,756.
- 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.
- the filter 10 may be configured to remove a desired amount of leukocytes.
- the filter is configured to remove greater than 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.
- the filter can be configured to provide a filtered fluid having about 1 x 10 4 leukocytes or less.
- the filter can be configured to provide a filtered fluid having about 1 x 10 3 leukocytes or less.
- the resultant filtered fluid has about 200 leukocytes/liter or less, preferably, about 100 leukocytes/liter or less. In some embodiments, the filtered fluid has about 75 leukocytes/unit (e.g., a unit having a volume of about 300 ml) or less.
- 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.
- the filtered fluid e.g., in the container downstream of the filter
- the resultant unit of filtered fluid has less than about 1 x 10 9 platelets.
- the resultant unit of filtered fluid has about 1 x 10 4 platelets, or less.
- the filter is configured to filter a suitable volume of fluid in a suitable amount of time.
- the filter can be capable of filtering about 200 to about 400 ml of fluid with a minimal effect on the overall processing time.
- 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.
- the filter is capable of filtering about 500 to about 1000 ml of fluid in about 25 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.
- 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.
- the second element 2 of the filter 10 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 fluid.
- 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.
- CWST critical wetting surface tension
- 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.
- 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.
- 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.
- 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.
- the first and/or second elements can be modified as described in, for example, the U.S. patents listed above.
- 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 about 7 to about 7.4) .
- 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
- physiological pH e.g., a pH of about 7 to about 7.4
- the first element 1 may be configured to remove a desired amount of leukocytes.
- 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.
- a leukocyte depletion medium suitable for passing the plasma in about one unit of biological fluid has, for example, a fiber surface area of from about 0.08 to about 1.4 M 2 /g, and in some embodiments, from about 0.1 to about 0.9 M 2 /g.
- a fiber surface area of from about 0.08 to about 1.4 M 2 /g, and in some embodiments, from about 0.1 to about 0.9 M 2 /g.
- an illustrative range for the relative voids volume is about 50% to about 92%, e.g., about 60% to about 89%.
- 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.
- the red cell barrier medium may allow a plasma-rich fluid to pass therethrough, abruptly stopping flow when red blood cells block the medium.
- the barrier medium By slowing the flow of the biological fluid, the barrier medium allows the operator to manually stop the flow to 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 medium.
- This embodiment of the invention allows the operator more time to intervene and stop the flow.
- 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 cell-containing fluid approaches the medium.
- a reduction in flow e.g., a 33% 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.
- 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.
- 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.
- 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 2 /g, and in some embodiments, about 0.06 to about 2.0 M 2 /g.
- 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 M 2 /g, e.g., from 0.25 to about 1.5 M 2 /g, or from about 0.35 to about 1.4 M 2 /g, e.g., 0.4 to 1.2 M 2 /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%.
- 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.
- the second element 2 comprises at least one, and in some embodiments, no more than one, membrane.
- the second element comprises a microporous polymeric membrane.
- the second element comprises a hydrophilic microporous polymeric membrane.
- 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.
- 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.
- 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.
- 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 .
- 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.
- undesirable material e.g., large particulate matter, microaggregates and/or blood cells.
- the second element can sieve out at least level of the undesirable material passing through the first element.
- 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.
- the second element can be treated for increased efficiency in processing a biological fluid.
- 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.
- the second element has an adsorption of proteinaceous material measured by the Bovine Serum Albumin
- 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/cm 2 , or less .
- the second element can have any suitable thickness.
- 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.
- 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.
- 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.
- the filter device or filter assembly 100 according to the invention 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.
- 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 3, wherein the components of the system are in fluid communication with each other via a plurality of conduits.
- 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) .
- 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.
- a sampling device 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) .
- additional filter devices including leukocyte depletion filter devices, (with and without filter bypass loops) .
- 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.
- 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.
- a sampling arrangement e.g., as disclosed in International Publication No. WO 98/28057
- needles and/or cannulas e.g., as disclosed in International Publication No. WO 98/28057
- a phlebotomy needle protector e.g., to reduce the level of leukocytes from a unit of biological fluid before further processing the fluid, or at least further processing one or more components of the fluid.
- a unit of biological fluid e.g., a unit of whole blood
- a leukocyte depletion filter device 200 that may also deplete platelets from the blood
- processing the unit of whole blood can include passing gas (e.g., air) through at 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 is preferably centrifuged to provide a supernatant layer comprising plasma-rich fluid, and a sediment layer comprising red blood cells.
- the plasma-rich fluid e.g., platelet-poor plasma
- 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.
- 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.
- an additive solution can be passed from third satellite bag 53 to be combined with the red cells in second satellite bag 51, and the red cells/additive solution can be stored until needed.
- 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 10 s 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.
- PPP platelet-poor-plasma
- 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 are no red cells in the fluid downstream of the filter visible to the technician operating the system.
- filter devices according to the invention can provide substantially cell-free plasma.
Landscapes
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Engineering & Computer Science (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Water Supply & Treatment (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Filtering Materials (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10297398P | 1998-10-02 | 1998-10-02 | |
US102973P | 1998-10-02 | ||
PCT/US1999/022478 WO2000020053A1 (en) | 1998-10-02 | 1999-09-29 | Biological fluid filter and system |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1123123A1 true EP1123123A1 (de) | 2001-08-16 |
Family
ID=22292695
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99948497A Withdrawn EP1123123A1 (de) | 1998-10-02 | 1999-09-29 | System und filter für biologische flüssigkeiten |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1123123A1 (de) |
JP (1) | JP2002526172A (de) |
KR (1) | KR20010075549A (de) |
AU (1) | AU763879B2 (de) |
CA (1) | CA2345535A1 (de) |
WO (1) | WO2000020053A1 (de) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1420796A (zh) | 2000-03-31 | 2003-05-28 | 巴克斯特国际公司 | 收集包括不含或实质上不含血细胞的血浆在内的减白细胞的血液组分的***及方法 |
ITTO20020736A1 (it) * | 2002-08-21 | 2004-02-22 | Fresenius Hemocare Italia Srl | Filtro per leucociti e suo impiego per l'impoverimento di prodotti del sangue da leucociti. |
JP4637476B2 (ja) * | 2002-12-19 | 2011-02-23 | 東京応化工業株式会社 | ホトレジスト組成物の製造方法 |
JP4637967B2 (ja) * | 2002-12-19 | 2011-02-23 | 東京応化工業株式会社 | ホトレジスト組成物の製造方法 |
DE10304365A1 (de) * | 2003-02-04 | 2004-08-05 | Ls-Medcap Gmbh | Filtervorrichtung |
CN102821796B (zh) * | 2010-03-31 | 2015-11-25 | 旭化成医疗株式会社 | 白血球去除器的启动加注***以及启动加注方法 |
US9796166B2 (en) | 2014-03-24 | 2017-10-24 | Fenwal, Inc. | Flexible biological fluid filters |
US10159778B2 (en) | 2014-03-24 | 2018-12-25 | Fenwal, Inc. | Biological fluid filters having flexible walls and methods for making such filters |
US10376627B2 (en) | 2014-03-24 | 2019-08-13 | Fenwal, Inc. | Flexible biological fluid filters |
US9968738B2 (en) | 2014-03-24 | 2018-05-15 | Fenwal, Inc. | Biological fluid filters with molded frame and methods for making such filters |
US9782707B2 (en) | 2014-03-24 | 2017-10-10 | Fenwal, Inc. | Biological fluid filters having flexible walls and methods for making such filters |
EP3220298A1 (de) | 2016-03-14 | 2017-09-20 | Fenwal, Inc. | Zellverarbeitungssystem und verfahren mit prozessparameterregelung |
US11191879B2 (en) | 2016-05-27 | 2021-12-07 | Fenwal, Inc. | Cell processing system and method with preliminary process evaluation |
US10654000B2 (en) | 2016-07-13 | 2020-05-19 | Fenwal, Inc. | Cell processing system and method with centralized data management, monitoring and/or control |
US20220241472A1 (en) * | 2021-02-03 | 2022-08-04 | Taiwan RedEye, Biomedical Inc. | Red blood cell filtering apparatus and system comprising the same |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4507119A (en) | 1982-07-06 | 1985-03-26 | E. I. Du Pont De Nemours And Company | Sterile docking process, apparatus and system |
EP0208004B1 (de) | 1985-07-05 | 1988-08-10 | NPBI Nederlands Produktielaboratorium voor Bloedtransfusieapparatuur en Infusievloeistoffen B.V. | Verfahren und Vorrichtung zum sterilen Docken von Kunststoffschlauchabschnitten oder dergleichen |
US4913756A (en) | 1987-09-22 | 1990-04-03 | Denco, Inc. | Techniques for welding thermoplastic tubes |
US4925572A (en) | 1987-10-20 | 1990-05-15 | Pall Corporation | Device and method for depletion of the leukocyte content of blood and blood components |
US4880548A (en) | 1988-02-17 | 1989-11-14 | Pall Corporation | Device and method for separating leucocytes from platelet concentrate |
JPH0614969B2 (ja) * | 1988-03-15 | 1994-03-02 | テルモ株式会社 | 液体濾過装置 |
US5344561A (en) * | 1989-05-09 | 1994-09-06 | Pall Corporation | Device for depletion of the leucocyte content of blood and blood components |
IL104670A (en) * | 1993-02-09 | 1998-04-05 | Travenol Lab Israel Ltd | Leukocyte removal method and filter unit for same |
AU5309396A (en) * | 1995-04-13 | 1996-10-30 | Travenol Laboratories (Israel) Ltd. | Leukocyte filtration method and apparatus |
CA2270413A1 (en) * | 1996-11-08 | 1998-05-14 | Chong-Son Sun | Method for purifying blood plasma and apparatus suitable therefor |
WO2015166839A1 (ja) | 2014-04-28 | 2015-11-05 | クラレケミカル株式会社 | エネルギー貯蔵デバイスの電極用多孔質炭素材料およびその製造方法 |
-
1999
- 1999-09-29 CA CA002345535A patent/CA2345535A1/en not_active Abandoned
- 1999-09-29 WO PCT/US1999/022478 patent/WO2000020053A1/en not_active Application Discontinuation
- 1999-09-29 JP JP2000573410A patent/JP2002526172A/ja not_active Withdrawn
- 1999-09-29 AU AU61661/99A patent/AU763879B2/en not_active Ceased
- 1999-09-29 EP EP99948497A patent/EP1123123A1/de not_active Withdrawn
- 1999-09-29 KR KR1020017004202A patent/KR20010075549A/ko not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO0020053A1 * |
Also Published As
Publication number | Publication date |
---|---|
AU6166199A (en) | 2000-04-26 |
JP2002526172A (ja) | 2002-08-20 |
WO2000020053A1 (en) | 2000-04-13 |
CA2345535A1 (en) | 2000-04-13 |
AU763879B2 (en) | 2003-07-31 |
KR20010075549A (ko) | 2001-08-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5616254A (en) | System and method for processing biological fluid | |
AU651646B2 (en) | System and method for processing biological fluids | |
US7361277B2 (en) | Biological fluid filter and system | |
US5258126A (en) | Method for obtaining platelets | |
KR101498138B1 (ko) | 세포 수확 장치 및 시스템 | |
AU763879B2 (en) | Biological fluid filter and system | |
US20060229547A1 (en) | Systems and methods for collecting leukocyte-reduced blood components, including plasma that is free or virtually free of cellular blood species | |
US20040118789A1 (en) | Biological fluid treatment system | |
US7140497B2 (en) | Selective deleukocytation unit for a platelet product | |
US5360545A (en) | Filter for obtaining platelets | |
US20060016753A1 (en) | Biological fluid filter | |
EP1171219B1 (de) | Filter und system zur filtration biologischer flüssigkeiten | |
CZ343991A3 (cs) | Způsob zpracování biologické tekutiny a zařízení k provádění tohoto způsobu |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20010430 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE |
|
AX | Request for extension of the european patent |
Free format text: AL;LT;LV;MK;RO;SI |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
18W | Application withdrawn |
Effective date: 20060609 |