WO1995002443A1 - Dispositif et procede pour le traitement d'un fluide biologique - Google Patents

Dispositif et procede pour le traitement d'un fluide biologique Download PDF

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Publication number
WO1995002443A1
WO1995002443A1 PCT/US1994/007750 US9407750W WO9502443A1 WO 1995002443 A1 WO1995002443 A1 WO 1995002443A1 US 9407750 W US9407750 W US 9407750W WO 9502443 A1 WO9502443 A1 WO 9502443A1
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WO
WIPO (PCT)
Prior art keywords
separation medium
plasma
biological fluid
separation
fluid
Prior art date
Application number
PCT/US1994/007750
Other languages
English (en)
Inventor
Vlado I. Matkovich
Thomas C. Gsell
David B. Pall
Thomas J. Bormann
Original Assignee
Pall Corporation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Pall Corporation filed Critical Pall Corporation
Priority to AU73980/94A priority Critical patent/AU7398094A/en
Publication of WO1995002443A1 publication Critical patent/WO1995002443A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/08—Prevention of membrane fouling or of concentration polarisation
    • 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
    • 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0413—Blood
    • A61M2202/0415—Plasma
    • 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
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/75—General characteristics of the apparatus with filters
    • A61M2205/7563—General characteristics of the apparatus with filters with means preventing clogging of filters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2321/00—Details relating to membrane cleaning, regeneration, sterilization or to the prevention of fouling
    • B01D2321/20—By influencing the flow
    • B01D2321/2066—Pulsated flow
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2321/00—Details relating to membrane cleaning, regeneration, sterilization or to the prevention of fouling
    • B01D2321/20—By influencing the flow
    • B01D2321/2083—By reversing the flow

Definitions

  • the present invention concerns a device and method for processing a biological fluid such as blood.
  • a biological fluid such as blood.
  • the present invention provides for separating plasma from a biological fluid.
  • a non-centrifugal technique for separating a biological fluid into one or more components is by passing the biological fluid through a separation device.
  • the separation device includes a porous membrane or the like which allows at least one component of the biological fluid to pass through the membrane while the remaining components of the fluid pass over or tangentially to the membrane.
  • whole blood or platelet-rich plasma may be directed into a separation device which allows a non-cellular component such as plasma to pass through the membrane.
  • Biological fluids include 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, fresh frozen plasma (FFP) , components obtained from plasma, packed red cells (PRC) , or buffy coat (BC) ; analogous blood products derived from blood or a blood component or derived from bone marrow; red cells separated from plasma and resuspended in physiological fluid; and platelets separated from plasma and resuspended in physiological fluid.
  • PC platelet concentrate
  • PRP platelet-rich plasma
  • PPP platelet-poor plasma
  • FFP fresh frozen plasma
  • PC buffy coat
  • the biological fluid may include leukocytes, or may be treated to remove, isolate, or obtain leukocytes or other components of the biological fluid.
  • blood product or biological fluid refers to the components 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 patient to patient and 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.
  • a plasma-depleted fluid refers to a biological fluid which has had some quantity of plasma-rich fluid (defined below) removed therefrom, e.g., the platelet-rich fluid or platelet component obtained when plasma is separated from PRP, or the fluid which remains after plasma is removed from whole blood.
  • the separation of the plasma-rich fluid from the biological fluid produces a plasma-depleted fluid having an increased concentration of platelets and/or red cells on a volume basis.
  • the plasma-depleted fluid is a platelet-containing fluid.
  • a plasma-rich fluid refers to the plasma portion or plasma component removed from a biological fluid, e.g., the plasma- rich fluid when plasma is separated from PRP, or the plasma which is removed from whole blood.
  • the plasma-rich fluid separated from a biological fluid is typically cell-free and has an increased concentration of plasma on a volume basis.
  • the plasma-rich fluid is the plas a- containing fluid that passes through a separation medium.
  • Exemplary plasma-rich fluids include platelet-poor plasma or platelet-free plasma.
  • a separation medium refers to at least one porous medium having a first surface and a second surface, and which separates at least one component of the biological fluid from another component by passing the biological fluid along the first surface of the separation medium, e.g., in a cross flow or tangential flow manner with respect to the porous medium.
  • the porous medium for use with a biological fluid may be formed from any natural or synthetic fiber or from a porous or permeable membrane (or from other materials of similar surface area and pore structure or arrangement, e.g., pore size or pore rating or pore diameter) compatible with a biological fluid, typically a biological fluid containing platelets and/or red blood cells, e.g, whole blood or PRP.
  • the surface of the fibers or membrane may be unmodified or may be modified to achieve a desired property.
  • the separation medium may remain untreated, the fibers or membrane are preferably treated to make them even more effective for separating one component of a biological fluid, e.g., plasma, from other components of a biological fluid, e.g., platelets or red cells.
  • the separation medium is preferably treated in order to reduce or eliminate platelet adherence to the medium. Any treatment which reduces or eliminates platelet adhesion is included within the scope of the present invention.
  • the medium may be surface modified in order to achieve a desired critical wetting surface tension (C ST) and to be less adherent of platelets, e.g., as disclosed in U.S. Patent Nos. 4,880,548 and 5,100,564, and International Publication No. WO 92/07656.
  • C ST critical wetting surface tension
  • a preferred range of CWST for a separation medium as provided by the present invention is above about 53 dynes/cm, typically above about 70 dynes/cm.
  • the CWST of the separation medium may be dictated by its intended use. Further, the medium may be subjected to gas plasma treatment, an exemplary purpose for which is to reduce platelet adhesion.
  • the porous medium may be pre-formed, single or multi-layered, and/or may be treated to modify the surface of the medium. If a fibrous medium is used, the fibers may be treated either before or after forming the fibrous lay-up. It is preferred to modify the fiber surfaces before forming the fibrous lay-up because a more cohesive, stronger product is obtained after hot compression to form an integral element.
  • the separation medium may be configured in any suitable fashion, such as a flat sheet, a composite of two or more layers, a corrugated sheet, a web, hollow fibers.
  • a preferred separation medium is configured as a membrane, more preferably, a planar membrane.
  • Exemplary separation media include but are not limited to those disclosed in International Publication Nos. WO 92/07656 and WO 93/08904, and U.S. Patents 4,886,836; 4,906,374; 4,964,989; 4,968,533; and 5,019,260, which may include separation media having a water permeability of up to about 0.023 L/min/Pa/m 2 (about 15.0 L/min/psid/ft 2 ) .
  • Tangential flow filtration refers to passing or circulating a biological fluid in a generally parallel or tangential manner to the surface of the separation medium.
  • the present invention provides a method for treating a biological fluid comprising passing a biological fluid along a first surface of a separation medium and passing a component of the biological fluid from the first surface of the separation medium through the separation medium to a second surface of the separation medium, and creating a pulsating reverse pressure differential between the first and second surfaces of the separation medium.
  • creating the pulsating reverse pressure differential between the first and second surfaces of the separation medium includes backflowing a portion of plasma through the separation medium.
  • at least one component of the biological fluid flows tangentially to the separation medium and another component flows through the porous medium, and the method includes directing a pulsating reverse pressure differential through the separation medium.
  • At least one component of the biological fluid flows along a first fluid flow path through the separation medium and the pulsating reverse pressure differential is directed opposite to the first fluid flow path.
  • the present invention provides a system for separating at least one component, e.g., plasma, from a biological fluid comprising a separation medium having a fluid flow path through the separation medium, and a pulsating reverse pressure differential generator.
  • the present invention provides a system for treating a biological fluid comprising a separation medium having first and second external surfaces and being suitable for passing plasma therethrough; a housing defining first and second flow paths, the separation medium being disposed within the housing wherein the first flow path extends from the first external surface through the separation medium to the second external surface and the second flow path extends tangentially to the first external surface of the separation medium; and a pulsating reverse pressure differential generator for directing a pulsating pressure differential against the second external surface.
  • This invention also provides for a device and method for separating platelet-poor plasma or platelet-free plasma from a biological fluid, such as PRP or from whole blood, without requiring rotation, spinning, or centrifugation to effect the separation.
  • the instant invention provides for the separation of plasma from whole blood or PRP without centrifugation.
  • the invention involves the treatment of a biological fluid to non- centrifugally separate at least one component from the biological fluid, e.g. , treating PRP to obtain plasma and PC, or separating plasma from whole blood.
  • a biological fluid to non- centrifugally separate at least one component from the biological fluid
  • Processes and devices provided by the invention utilize a separation medium that allows the passage of plasma through the medium while subjecting the medium to a pulsating reverse pressure differential. Tangential flow of a biological fluid parallel to the upstream surface of the separating medium permits the passage of plasma through the medium, while reducing the tendency for cellular components or platelets to adhere to the surface of the medium, thus assisting in preventing or reducing clogging or fouling of the separation medium.
  • the device and method of the present invention thus protect components of the biological fluid, e.g., platelets and red blood cells, from physiological damage, and directly and effectively minimize or eliminate loss or damage caused by the currently used centrifugal separation processes, by reducing or eliminating the exposure to harmful centrifugation. Furthermore, the platelets and/or red blood cells are not required to pass through yet another filtration device in order to be separated from PRP.
  • An advantage of the present invention may include the increased yield of clinically and therapeutically superior platelet concentrate and/or platelet-free (or platelet-poor) plasma.
  • Advantageous features of the devices and methods of the present invention include the separation of at least one component of a biological fluid from the rest of the fluid with minimal loss or activation of platelets and with minimal loss of separation medium efficiency. Further, a device as provided by this invention can deliver a higher proportion of the platelets, particularly the younger platelets, or plasma originally present in the sample. The present invention further provides for maximum recovery of plasma from whole blood or from PRP.
  • Figure 1 is a schematic representation of an embodiment of the present invention.
  • Figure 2 is a schematic representation of another embodiment of the present invention.
  • Figure 3 is a schematic representation of another embodiment of the present invention.
  • Figure 4 is schematic representation of an exemplary device for generating a pulsating reverse pressure differential.
  • the present invention involves the separation of one or more components from a biological fluid.
  • a biological fluid particularly blood
  • a separation medium suitable for passing plasma therethrough. Clogging of the separation medium may be minimized or prevented by treating the separation medium to reduce platelet adhesion and/or by directing a pulsating reverse pressure differential through the separation medium.
  • Biological fluid processing system 100 may include a first container such as a collection bag or syringe 19; a separation device 200 including a separation medium 16; a second container (first satellite bag) 18; and a third container (second satellite bag) 17.
  • a device for directing a pulsating reverse pressure differential through the separation medium is positioned between the separation device 200 and the second or third container.
  • the pulsating reverse pressure differential generator is a pump 400, preferably a modified peristaltic pump.
  • the processing system 100 may also include at least one functional biomedical device, for example, a pump 90, and/or other functional biomedical devices, including filtration and/or separation devices (not shown) .
  • the components of the biological fluid processing system may be in fluid communication through conduits.
  • conduits 50A, 50B, and 50C may be used to provide fluid communication between the components of the system.
  • the biological fluid processing system may also include a seal, valve, check valve, clamp, transfer leg closure, stopcock, or the like located within or on at least one of the conduits and/or the containers.
  • a separation device as provided by the invention generally comprises a housing 10 which includes an inlet 11 and first and second outlets 12 and 13, respectively; a first fluid flow path 14 between the inlet 11 and the second outlet 13; and a second fluid flow path 15 between the inlet 11 and the first outlet 12.
  • a separation medium 16 having first and second surfaces 16a, 16b is positioned inside the housing 10, the separation medium being positioned across the first fluid flow path 14 and parallel to the second fluid flow path 15.
  • second container 18 may be squeezed to generate a pulsating reverse pressure differential.
  • the housing 10 preferably includes first and second portions 10a and 10b, and the separation medium 16 is positioned inside the housing 10 between the first and second housing portions 10a, 10b.
  • the first and second housing portions 10a, 10b may be joined in any convenient manner, for example, by ultrasonic or heat welding, an adhesive, a solvent, or one or more connectors.
  • Figure 3 illustrates an exemplary system for processing whole blood into each of its components.
  • the system includes a collection bag or first container 30, second container 31, third container 32, separation device 33, fourth container 34, and pumps 300 and 400.
  • the system may also include: a red cell barrier medium 35 and/or a leukocyte depletion filter (not shown) between the first container 30 and the second container 31; a leukocyte depletion filter 36 between the first container 30 and the third container 32; and a leukocyte depletion filter 37 between first container 31 and the inlet 11 of the separation device 33.
  • Figure 4 illustrates an exemplary device for producing a pulsating reverse pressure differential.
  • the exemplary device preferably a peristaltic pump 400, includes a housing 401, a channel or guide 402 suitable for properly positioning a conduit 403, and a roller 404 connected to a rotor 405.
  • the rotation of the rotor 405 engages the roller 404 with the conduit 403, preferably at a predetermined interval and for a predetermined period.
  • any device or assembly which creates a pulsating reverse pressure differential is suitable for use in the invention.
  • Typical devices include, but are not limited to a pump such as a peristaltic pump, a check valve, a float valve and the like.
  • the number, type and location of the devices as well as the manner of creating the pulsating reverse pressure differential may be varied according to its intended use.
  • at least one reverse pressure differential creating device 400 such as a peristaltic pump, may be located between the separation assembly 33 and container 34, to provide backflow across the separation medium.
  • a pressure differential generator 300 such as a peristaltic pump, but may not require pump 400.
  • a reverse pressure differential through the separation medium may be generated by restricting the flow upstream of pressure differential generator 300 and stopping backflow through outlet 12.
  • the system may include a variable restriction flow control device 301 positioned upstream of the pressure differential generator 300, and a check valve 302, or the like, positioned in the conduit communicating with outlet 12.
  • the pulsating reverse pressure differential generator provides pulsed backflow through the separation medium in the separation device 33 and/or 200 while there is continuous transverse or cross flow across the first surface of the separation medium.
  • pulsed and pulsating refer to any non-continuous, periodic, or intermittent backflow through the separation medium.
  • a typical pulsating reverse pressure differential generator provides a reverse pressure differential of relatively short duration, for example, from about .01 seconds to about 5 seconds, more preferably from about .01 seconds to about 1 second.
  • pulsed backflow may be provided by a reverse pressure differential creating device 400, while transverse flow may be provided by a pressure differential creating device 300.
  • Embodiments of the present invention may also be configured in a variety of ways to expose the separation medium 16 to back pressure or backflow to prevent or reduce fouling of surface 16a, while minimizing hold-up volume.
  • a peristaltic pump providing less than a 100% duty cycle may be utilized to provide for pulsed backflow.
  • a duty cycle of less than about 75%, more preferably, less than about 50%, may be utilized.
  • a peristaltic pump 400 utilizing a single roller may be used.
  • Multi-roller peristaltic pumps may also be used, preferably after removing at least one roller.
  • devices 300 and 400 may both comprise peristaltic pumps, in a preferred embodiment, device 300 may be a multi- roller peristaltic pump, while device 400 may be a single roller peristaltic pump as described above.
  • any separation device may be used which directs a portion of a biological fluid tangentially or in a crossflow manner across a separation medium, while at the same time directing another portion of the biological fluid through the separation medium.
  • Exemplary separation devices include but are not limited to the devices and assemblies disclosed in International Publication Nos. WO 93/08904 and WO 92/07656.
  • the separation medium includes channels which separate the inlet flow of biological fluid into separate flow paths tangential to the first surface 16a of the separation medium 16 and across separation medium 16.
  • the plasma depleted fluid passing tangentially across the separation medium may be repeatedly recirculated through the separation device.
  • the separation device may include an arrangement of ribs or may comprise one or more channels, grooves, conduits, passages, or the like which may be serpentine, parallel, curved, spiral, or have a variety of other configurations facing the second surface 16b of the separation medium.
  • the housing and the separation medium of the present inventive device may be of any suitable configuration and material.
  • the housing, including the channels, ribs, walls, and/or projections may be formed from a material that is substantially impermeable to the biological fluid and substantially unreactive with the biological fluid.
  • the channels may be defined by two substantially impermeable and substantially unreactive sides and two permeable sides.
  • the opposing sides of a channel may each face a separation medium, allowing plasma-rich fluid to flow through each separation medium, and plasma-depleted fluid to flow tangentially to each separation medium.
  • At least one side of the channel is substantially impermeable to and substantially unreactive with the biological fluid.
  • the preferred device has one inlet and two outlets, other configurations can be employed without adversely affecting the proper functioning of the device.
  • multiple inlets for a biological fluid may be used so long as the biological fluid flows tangentially to the face of the separation medium.
  • a single inlet and a single outlet may be used.
  • a separation device may be configured to provide for two liquid flow paths such that both liquid flow paths communicate with the inlet, but only one liquid flow path communicates with both the inlet and the outlet.
  • the separation medium may be arranged in the separation device in any suitable manner so long as the biological fluid flow tangential or parallel to the separation medium is maintained to a sufficient extent to avoid or minimize substantial platelet and/or red cell adhesion to the separation medium.
  • platelet adhesion may be controlled or affected by manipulating any of a number of factors: velocity of the fluid flow, configuration of the channel, depth and/or width of the channel, varying the depth and/or varying the width of the channel, the surface characteristics of the separation medium, the smoothness of the medium's surface, and/or the angle at which the fluid flow crosses the face of the separation medium, among other factors.
  • platelets may not adhere as readily to a separation medium having a smooth surface as compared to a medium having a rougher surface.
  • a desired velocity may be achieved by manipulating these and other elements.
  • a separation medium comprises a porous medium suitable for passing a component of a biological fluid, such as a plasma-rich fluid, therethrough.
  • separation media in accordance with the invention separate plasma from a biological fluid containing platelets, typically whole blood or PRP.
  • the separation medium may include but is not limited to polymeric fibers (including hollow fibers) , polymeric fiber matrices, polymeric membranes, and solid porous media.
  • a separation medium according to the invention preferably exhibits a pore structure or arrangement, such as, for example, an average pore rating that is generally or intrinsically smaller than the average size of platelets.
  • a typical separation device as provided by the invention includes an effective pore size smaller than platelets on the average, typically less than about 4 micrometers, preferably less than about 2 micrometers.
  • platelets do not adhere to the surface of the separation medium, thus reducing pore blockage.
  • the separation medium should also have a low affinity for proteinaceous components in the biological fluid, and preferably is of sufficient size to prevent the passage of viruses, bacteria, or the like. This enhances the likelihood that the plasma- rich fluid, e.g. , platelet-free plasma, will exhibit a normal concentration of proteinaceous clotting factors, growth factors, and other needed components.
  • the separation medium and device also enhances the likelihood that complement activation will be avoided.
  • a separation medium formed of fibers may be continuous, staple, or melt-blown.
  • the fibers may be made from any material compatible with a biological fluid containing platelets, and may be treated in a variety of ways to make the medium more effective. Also, the fibers may be bonded, fused, or otherwise fixed to one another, or they may simply be mechanically entwined.
  • a separation medium may refer to one or more porous polymeric sheets, such as a woven or non-woven web of fibers, with or without a flexible porous substrate, or may refer to a membrane formed, for example, from a polymer solution in a solvent by precipitation of a polymer when the polymer solution is contacted by a solvent in which the polymer is not soluble.
  • the porous, polymeric sheet will typically be microporous, e.g., having a substantially uniform, continuous matrix structure containing a myriad of small largely interconnected pores.
  • a preferred separation medium of this invention may be formed, for example, from any synthetic polymer capable of forming fibers or a membrane.
  • Preferred polymers include, but are not limited to polyolefins, polyesters, and polyamides, e.g., polybutylene terephthalate (PBT) and nylon.
  • a polymeric membrane may also be formed from a fluorinated polymer such as polyvinylidene difluoride (PVDF) .
  • the most preferred separation media are a microporous polyamide membrane or a polycarbonate membrane.
  • the separation medium may be surface modified, typically by radiation grafting or gas plasma treatment, in order to achieve the desired performance characteristics, whereby platelets are concentrated with a minimum of medium blocking.
  • a typical separation device as provided by the invention includes a separation medium having an effective surface area in the range of about 1.94 cm 2 to about 194 cm 2 (about 0.3 in 2 to about 30 in 2 ).
  • the term effective surface area refers to the surface area contacted by the biological fluid.
  • a preferable ratio of the wetted surface area of the fluid flow channel to the volume of the channel (A/V) is in the range of about 6.3 cm" 1 to about 866 cm “1 (about 16 in "1 to about 2,200 in” 1 ).
  • the permeability and size of a typical separation device as provided by the present invention is preferably sufficient to produce about 160 cc to about 240 cc of plasma at reasonable pressures (e.g., less than about 6.9 x 10 s Pa (100 psi), more preferably, less than about 1.38 x 10 5 (20 psi) in a reasonable amount of time (e.g., less than about one hour) .
  • the permeability of the separation medium is sufficient to allow the passage of a desirable amount of a fluid therethrough at a reasonable pressure in a reasonable amount of time.
  • a preferred permeability is in the range of from about 0.00078 L/min/Pa/m 2 to about 0.023 L/min/Pa/m 2 (about 0.5 to about 15.0 L/min/psid/ft 2 ) .
  • a preferred permeability is in the range of from about 0.00078 L/min/Pa/m 2 to about 0.0078 L/min/Pa/m 2 (about 0.5 to about 5.0 L/min/psid/ft 2 ), more preferably in the range of about 0.0011 L/min/Pa/m 2 to about 0.0047 L/min/Pa/m 2 (about 0.7 to about 3.0 L/min/psid/ft 2 ) .
  • the separation device may be positioned in the system of the instant invention in a variety of locations, as illustrated by Figures 1-3. It is intended that the invention is not to be limited by the location or position of the separation device.
  • a system as provided by the present invention may be used in conjunction with other functional biomedical devices, including filtration and/or separation devices, e.g., a device for removing leukocytes from a platelet-containing fluid or platelet concentrate. An example of a system is shown in Figure 3. Exemplary functional biomedical devices are disclosed in U.S.
  • a functional biomedical device refers to any of a number of devices, assemblies, or systems used in the collection and/or processing of biological fluids, such as whole blood or a blood component.
  • Exemplary functional biomedical devices include biological fluid containers, such as collection or source and satellite bags, such as first container (30) , transfer (31, 32) , and storage bags (not shown) ; conduits and connectors interposed between the containers; clamps, closures, and the like; vents and gas manipulation devices, such as air or gas inlet or outlet devices; a debubbler; one or more pumps (300, 400) ; and a red cell barrier medium or assembly (35) .
  • the functional biomedical device may also include a device for destroying biological contaminants, such as a high intensity light wave chamber, or a device for sampling a biological fluid.
  • the present inventive device may similarly be part of an apheresis system.
  • the biological fluid to be processed, the platelet-rich solution, and/or the platelet-poor solution may be handled in either a batch or continuous manner.
  • the sizes, nature, and configuration of the present inventive device can be adjusted to vary the capacity of the device to suit its intended environment.
  • the processing of biological fluid in the context of the present invention may take place at any suitable time, which may be soon after donation.
  • the biological fluid is donated whole blood, it is typically processed as soon as practicable in order to maximize the number of components derived and to maximize blood component viability and physiological activity.
  • Early processing may more effectively reduce or eliminate contaminating factors, including, but not limited to, leukocytes and microaggregates.
  • Methods according to the invention include passing a biological fluid through a separation device, and subjecting the separation medium to a pulsating reverse pressure differential.
  • the method may include directing a portion of the biological fluid across a separation medium, and directing a pulsating reverse pressure differential against a downstream surface of the separation medium, thereby subjecting the portion of the biological fluid which passes through the separation medium to a pulsating reverse pressure differential.
  • the pulsating reverse pressure differential provides for backflowing a portion of plasma through the separation medium, i.e., backflowing plasma from the second surface of the separation medium to the first surface of the medium. Exemplary methods as provided by the invention may be described in more detail by referring to Figures 1-3.
  • Movement of the biological fluid through the device and/or through the system may be effected by maintaining a pressure differential between a container such as a collection bag or a syringe containing the biological fluid, and the destination of the biological fluid (e.g., a container such as a satellite bag) , to cause the fluid to flow in a desired direction.
  • exemplary means for creating this pressure differential may be by gravity head, applying pressure to the container (e.g., by hand or with a pressure cuff) , by placing the satellite bag in a chamber which establishes a pressure differential between the satellite bag and the collection bag, e.g., a vacuum chamber or by a pump. It is intended that the present invention is not to be limited by the means of creating the pressure differential.
  • a unit of a biological fluid (e.g., donor's whole blood, or PRP) may be received into a first container 19 such as a collection bag or syringe for processing.
  • the biological fluid is processed by directing it from the container 19 to separation medium 16 so that the biological fluid flows tangentially to the surface of the separation medium.
  • Directing the biological fluid to the separation medium may include channelling the biological fluid tangentially to the surface of the separation medium such that a plasma- depleted fluid passes tangentially across the separation medium and a plasma-rich fluid passes through the separation medium.
  • the fluid enters the separation device 200 and a portion of the biological fluid passes tangentially or parallel to the first surface 16a of the separation medium 16 on the way to the first outlet 12 via the second fluid flow path 15. Another portion of the biological fluid passes through the separation medium 16 and is directed toward the second outlet 13 via the first fluid flow path 14.
  • a plasma-depleted fluid e.g., a platelet-containing fluid
  • plasma-rich fluid exits the housing 10 at the second outlet 13.
  • the plasma-rich fluid may be stored in a region separated from the separation medium.
  • the plasma-rich fluid exiting at the second outlet 13, and/or the plasma-depleted fluid exiting at the first outlet 12, may be further processed.
  • additional processing may include collecting the fluids in separate containers, such as first satellite bag 18 and second satellite bag 17.
  • additional processing may include re-directing the plasma-depleted fluid to the separation medium to deplete additional amounts of plasma.
  • the plasma-depleted fluid may be repeatedly recirculated through the separation device, e.g., until the plasma-depleted fluid contains a pre-determined amount or concentration of the desired component, e.g., platelets.
  • a biological fluid such as whole blood is collected in first container 30.
  • the biological fluid may then be separated into a supernatant layer and a sediment layer, typically by subjecting the biological fluid to centrifugation.
  • the supernatant layer is then passed into second container 31, preferably making sure to prevent any of the sediment layer from passing into the second container 31, either by clamping the conduit at the appropriate time, or by including in the system a red cell barrier medium.
  • the sediment layer is then passed into third container 32. After the transfer of the sediment layer into third container 32 is completed, third container 32 may be separated from the system and removed for further processing.
  • the supernatant layer present in second container 31 is further processed by passing it through the separation device 33.
  • Pump 300 draws the supernatant from second container 31 and delivers it to the separation device at inlet 11. A portion of the supernatant layer passes tangentially to a separation medium and passes out of the separation device 33 through outlet 12. This portion of the supernatant layer may be recirculated through the separation assembly, as shown.
  • Another portion of the supernatant layer passes through the separation medium and passes out of the separation device 33 through outlet 13.
  • the differential pressure created by pump 300 will direct most of this fluid into fourth container 34, but, in accordance with the invention, some of this fluid will be pulsated back, preferably using pump 400, in the direction of the separation medium.
  • establishing a tangential flow of the biological fluid being processed parallel with or tangential to the face of the separation medium minimizes platelet collection on or in the separation medium. It is believed that maintaining a uniformly high velocity of the fluid across the entire surface of the separation medium reduces or eliminates eddies or stagnant areas of the biological fluid develop where platelets, red cells, or other material may settle upon, stick to, and foul the separation medium.
  • Fluid flow channels may also be utilized on the side of the separation medium opposite the biological fluid tangential flow to control the flow rate and pressure drop of a platelet-poor fluid, such as plasma.
  • passing biological fluid through the separation device 33 includes providing a reverse pressure differential across the separation medium, e.g., by creating a backflow across the medium or against surface 16b.
  • a reverse pressure differential may provide for minimizing platelet adhesion to, or contact with, the separation medium.
  • the reverse pressure differential may also provide for minimizing clogging of the separation medium by blood components such as platelets and/or red cells.
  • the biological fluid may be supplied in any suitable quantity consistent with the capacity of the overall device and by any suitable means, e.g., in a batch operation by, for example, a blood bag connected to an expressor or a syringe, or in a continuous operation as part of, for example, ah apheresis system.
  • any suitable means e.g., in a batch operation by, for example, a blood bag connected to an expressor or a syringe, or in a continuous operation as part of, for example, ah apheresis system.
  • the filtered PRP unit was then placed in a pressure cuff to which a pressure of 300 mm Hg was applied.
  • the tubing exiting the bag (clamped closed at this point) was connected to the inlet port of a separation device as shown in Figures 3-6 of International Publication No. WO 93/08904.
  • a microporous polyamide membrane having a pore rating of 0.65 microns was used as the separation medium in the device.
  • the area of the membrane was about 17.4 square centimeters.
  • the depth of the first fluid flow path channels decreased from about 0.03 cm near the inlet to about 0.01 cm near the outlet.
  • the depth of the second fluid flow path channels was about 0.025 cm.
  • the width of the channels was 0.084 cm.
  • the outlet ports of the device were connected to tubing which allowed the volume of fluid exiting the device to be measured and saved for analysis.
  • the test of the present invention was started by opening the clamp and allowing PRP to enter the device. Clear fluid (plasma) was observed to exit one port, and turbid fluid (platelet concentrate) exited the other port.
  • the clear fluid passed from the separation device through a conduit to a receiving bag. Interposed between the exit port of the separation device and the receiving bag was a peristaltic pump which periodically pulsed a portion of the clear fluid back into the separation device.
  • the duration of the test was 42 minutes, during which 154 ml of plasma and 32 ml of platelet concentrate was collected.
  • the concentration of platelets in the plasma was found to be 1.2 x 10 4 / ⁇ l, while the concentration of platelets in the platelet concentration was found to be 1.43 x 10 6 / ⁇ l.
  • a sample of 450 ml of whole blood was collected under standard conditions from a human donor and placed in a typical flexible plastic blood bag. An analysis of the whole blood sample indicates that it contained about 203 ml plasma.
  • a 2 cc whole blood sample was withdrawn from the bag in a 5 cc syringe and attached to the inlet port of a device as provided by the invention as shown in Figure 2.
  • the present inventive device included a serpentine fluid flow path with a channel length of 32.5 cm, a constant width of 0.081 cm, and a constant depth of 0.013 cm.
  • the fluid flow path was of a H C" cross-section and, on its open side, contacted a microporous polycarbonate membrane having a pore rating of 0.4 microns which served as the separation medium.
  • About 26.4 cm 2 of the microporous membrane were thereby part of the fluid flow path and were capable of being contacted by the whole blood sample or processed fluid as it passed through the device in the fluid flow path.
  • Fluid flowed through the separation medium at a rate of 0.2 ml/min. Satellite bag 18 was repeatedly lightly squeezed to induce clear fluid in the conduit to briefly flow back into the separation medium.
  • the entire whole blood sample was processed in about 2 minutes. Air in the syringe was used to drive any hold-up through the device.
  • a total of about 1.6 cc of turbid fluid (red cell containing fraction) and .4 cc of clear fluid was collected from the processing of the whole blood sample. An analysis of the clear fluid indicated that it was plasma.
  • EXAMPLE 3 A source bag and a satellite bag were connected to a separation device and a peristaltic pump in a configuration similar to that of Figure l.
  • the source bag contained a unit of leukocyte depleted PRP (approximately 200 ml) .
  • Tubing connected the source bag to the inlet port of the separation device, and, to provide for recirculation, tubing connected the first outlet port of the separation device to the source bag. Additionally, tubing connected the second outlet port of the separation device to the satellite bag.
  • a first peristaltic pump was associated with the tubing between the source bag and the inlet port of the separation device to provide for fluid flow.
  • a second peristaltic pump was associated with the tubing between the outlet port of the separation device and a satellite bag (for receiving plasma) to provide a pulsating reverse pressure differential.
  • the satellite bag was placed on a scale so that the amount of plasma entering the bag could be monitored.
  • the first peristaltic pump was activated at a flow rate of 25 cc/min and PRP was drawn from the source bag into the device.
  • Clear fluid (plasma) exited the second port and entered the satellite bag.
  • Turbid fluid (containing platelets) exited the first port and was recirculated into the source bag.
  • the source bag was periodically squeezed to increase the mixing of the platelets in the fluid. After approximately 35 minutes, about 150 ml of plasma was collected in the satellite bag and about 50 ml of platelet concentrate was collected in the source bag.

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  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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Abstract

On décrit un dispositif et un procédé pour le traitement d'un fluide biologique. Le fluide biologique est dirigé sur une première surface (16a) d'un milieu de séparation (16), afin que le fluide riche en plasma passe à travers le milieu de séparation (16) et que le fluide appauvri en plasma passe le long de la surface de séparation (16a) du milieu de séparation (16). On crée un différentiel de pression inverse pulsé entre la première et la seconde surfaces (16a, 16b) du milieu de séparation (16). Une partie du fluide riche en plasma soumis à ce différentiel de pression inverse pulsé est ainsi retournée à travers le milieu de séparation (16).
PCT/US1994/007750 1993-07-13 1994-07-12 Dispositif et procede pour le traitement d'un fluide biologique WO1995002443A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU73980/94A AU7398094A (en) 1993-07-13 1994-07-12 Device and method for processing biological fluid

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US9094193A 1993-07-13 1993-07-13
US08/090,941 1993-07-13

Publications (1)

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WO1995002443A1 true WO1995002443A1 (fr) 1995-01-26

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CA (1) CA2110569A1 (fr)
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000062840A1 (fr) * 1999-04-20 2000-10-26 Heim Medizintechnik Gmbh Dispositif pour diviser le sang en ses composants individuels et/ou en groupes de ceux-ci
EP1757356A1 (fr) * 2005-08-26 2007-02-28 Krones AG Appareil de filtration avec dispositif de pompage
WO2014093845A1 (fr) * 2012-12-14 2014-06-19 Bhc Technology Holdings Llc Isolement et concentration de cellules sanguines sur le lieu d'intervention
CN114030772A (zh) * 2021-09-30 2022-02-11 安徽省含山县油脂有限公司 一种大豆油生产用真空储油罐

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4751007A (en) * 1987-03-27 1988-06-14 Takeshi Kobayashi Method for filtering Bacillus subtilis
US4800022A (en) * 1985-03-13 1989-01-24 Baxter International Inc. Platelet collection system
US5217627A (en) * 1990-11-06 1993-06-08 Pall Corporation System and method for processing biological fluid

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4800022A (en) * 1985-03-13 1989-01-24 Baxter International Inc. Platelet collection system
US4751007A (en) * 1987-03-27 1988-06-14 Takeshi Kobayashi Method for filtering Bacillus subtilis
US5217627A (en) * 1990-11-06 1993-06-08 Pall Corporation System and method for processing biological fluid

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000062840A1 (fr) * 1999-04-20 2000-10-26 Heim Medizintechnik Gmbh Dispositif pour diviser le sang en ses composants individuels et/ou en groupes de ceux-ci
EP1757356A1 (fr) * 2005-08-26 2007-02-28 Krones AG Appareil de filtration avec dispositif de pompage
WO2007022868A1 (fr) * 2005-08-26 2007-03-01 Krones Ag Dispositif filtre pour un ensemble pompe
WO2014093845A1 (fr) * 2012-12-14 2014-06-19 Bhc Technology Holdings Llc Isolement et concentration de cellules sanguines sur le lieu d'intervention
CN114030772A (zh) * 2021-09-30 2022-02-11 安徽省含山县油脂有限公司 一种大豆油生产用真空储油罐
CN114030772B (zh) * 2021-09-30 2023-03-21 安徽省含山县油脂有限公司 一种大豆油生产用真空储油罐

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AU7398094A (en) 1995-02-13
CA2110569A1 (fr) 1995-01-14

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