AU2003213758A1

AU2003213758A1 - Compound removal device

Info

Publication number: AU2003213758A1
Application number: AU2003213758A
Authority: AU
Inventors: Robin G Pauley; Shmuel Sternberg
Original assignee: Fenwal Inc
Current assignee: Fenwal Inc
Priority date: 2002-03-14
Filing date: 2003-03-06
Publication date: 2003-09-29
Also published as: CA2477946A1; JP2005519744A; EP1487559A4; WO2003078023A1; EP1487559A1

Description

WO 03/078023 PCT/US03/06922 -1 COMPOUND REMOVAL DEVICE CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of United States Provisional Patent Application Serial No. 60/364,289, filed March 14, 2002. [0002] The present invention relates to devices for removing compounds from a fluid, such as blood or other biological fluid. The present invention also relates to methods for making such devices. BACKGROUND [0003] Significant advances have been made in the field of treating biological fluids, such as blood, to remove pathogens or other unwanted substances from the fluid. Many of the pathogen removal treatments developed or under development utilize one or more chemical compounds that eradicate or inactivate the pathogen. The chemical compound may act directly on the pathogen or may require stimulation from an energy source (such as light) before acting on the pathogen. [0004] After treatment, some of the compound used in the pathogen inactivation treatment may remain in the biological fluid as unreacted compound or as a reactive derivative thereof. Although most of the compounds presently used are not harmful to the recipient of the treated biological fluid, there is still a desire to remove or reduce the concentration of such compounds and their derivatives. Accordingly, as research and development in the field of pathogen inactivation continue, methods and devices for the removal of these compounds ("removal devices") have also been developed. [0005] Many of the known removal devices include an adsorptive or absorbtive material ("sorbent") that removes or binds the selected compound. The sorbent is often combined or carried by a support and/or placed inside a WO 03/078023 PCT/US03/06922 -2 container or a housing. Removal devices may be a "batch type" or "flow through" device. [0006] In a batch-type device, the biological fluid that has been treated in a pathogen inactivation treatment remains in contact with the sorbent for a pre-determined period of time. The container with the biological fluid and the removal device may be agitated to maximize exposure of the biological fluid to the sorbent of the removal device. [0007] In the "flow-through" system, the removal device is typically placed in the line of flow of the biological fluid. For example, the sorbent may be contained in a housing that has an inlet port and outlet port. A container containing a biological fluid with the pathogen inactivation compound or a derivative may be attached, by plastic tubing, to the inlet port. Another container for receiving the biological fluid may be likewise attached to the outlet port of the housing. As fluid flows from one container to the other, it contacts the sorbent of the removal device. Thus, compounds are removed, and a substantially compound-free biological fluid is collected in the receiving container. [0008] Examples of a removal device using sorbents that can remove compounds from a biological fluid are described in the patent literature. Many of these patents describe removal devices that use a particulate sorbent material, such as activated charcoal, porous silica, ion-exchange resins, or the like. [0009] In U.S. Patent No. 4,728,432, the removal device consists of a porous membrane containing an adsorbent in the form of a powder or fine particles combined with a polymeric material such as polyurethane to form the porous membrane. The membrane is fixed on a support having a net structure. The "absorber" (membrane and support) may be rolled or superposed into multiple layers and then housed in a vessel having an inlet and an outlet for the blood to WO 03/078023 PCT/US03/06922 -3 provide a flow-through device. Similar flow-through devices using activated charcoal are described in U.S. Patent Nos. 5,660,731 and 5,639,376. [0010] Compound removal devices are also described in U.S. Patent Application Serial No. 09/112,068 filed July 8, 1998 and U.S. Patent Application Serial No. 09/112,400, also filed July 8, 1998, both of which are incorporated herein by reference in their entireties. These patent applications disclose and describe flow-through and batch type devices for removing compounds used in pathogen inactivation treatments. The removal devices disclosed therein utilize activated charcoal as the sorbent or synthetic, microporous sorbent beads. In particular, the devices disclosed use beads made from polyaromatic absorbents comprising a hyper cross-linked polystyrene network. [0011] The batch-type device described in U.S. Patent Application Serial No. 09/112,400 can be formed in one of many different ways. In one preferred way of preparing the batch-type device, synthetic, microporous sorbent particles are immobilized within an inert matrix by, for example, combining the sorbent particles with a binding material and sintering the combination to form an adsorbent wafer. Thus, the sintered wafer has sorbent particles in the wafer interior and on the wafer surface to maximize contact of the biological fluid with the sorbent particles. The wafer may be placed inside a mesh pouch or other liquid permeable enclosure to ensure that any loose particulate from the wafer does not pass into the biological fluid. [0012] In a flow-through type device, the beads are packed in a column having an inlet and an outlet for introducing and removing the biological fluid. In an alternative embodiment, the sorbent beads may be finely ground and then combined with the binding material to form a wafer. The wafer is placed inside a flow-through housing.

WO 03/078023 PCT/US03/06922 -4 [0013] Whether the removal device includes activated charcoal or synthetic beads as the sorbent particulate, one potential concern with such devices is particle shedding. Thus, it would be desirable to provide a compound removal device where shedding of particulate is minimized. [0014] Another potential drawback with some of the existing compound removal devices is the cost of manufacture. A removal device that requires, for example, many beads (due to, for example, low surface area contact of the beads with the biological fluid) may increase the cost of making a compound removal device. Furthermore, additional steps such as sintering the sorbent particles with the polymeric material may also increase the cost. SUMMARY OF THE INVENTION [0015] In one aspect, the present invention is directed to a device for removing a compound from a fluid. The device includes at least one support surface and a plurality of sorbent particles carried by said support surface. The particles on said support surface have a masked area wherein the particles contact the support surface and an unmasked area not in contact with the support surface. [0016] In a further aspect, the present invention is directed to a sorbent core for use with a compound removal device. The core includes a plurality of layers, wherein each layer comprises a sheet having first and second sides with a plurality of sorbent particles attached to at least one of the sides to provide alternating portions of the sheets and particles. [0017] In a further more specific aspect of the present invention, the sorbent core may be associated with inlet and outlet ports to provide a flow-through compound removal device. [0018] In a still further aspect, the present invention is directed to a method of making a device for removing a compound from a fluid. The method includes providing a WO 03/078023 PCT/US03/06922 -5flexible support sheet having first and second oppositely facing sides wherein at least one of the sides comprises an adhesive surface. The method further includes applying a plurality of sorbent particles to the adhesive surface. BRIEF DESCRIPTION OF THE DRAWINGS [0019] Figure 1 is a plan view of a plastic container for holding a biological fluid and including a removal device embodying the present invention; [0020] Figure 2 is a plan view of a removal device embodying the present invention housed inside a mesh or other liquid permeable pouch; [0021] Figure 3 is a perspective view of a removal device embodying the present invention; [0022] Figure 4 is a plan view of a support for use in the present invention, having adhesive surfaces and protective backing films thereon; [0023] Figure 5 shows a disc-shaped compound removal device embodying the present invention; [0024] Figure 6 is a side view of the removal device of Figure 5; [0025] Figure 7 is a plan view of a biological fluid processing set including containers and a flow-through removal device embodying the present invention; [0026] Figure 8 is a plan view of a flow-through removal device embodying the present invention; [0027] Figure 9 is a cross-sectional view of the removal device of Figure 8; [0028] Figure 10 is a side view of a support sheet with sorbent particles applied thereon; [0029] Figure 11 is a plan view of the sheet of Figure 10 rolled onto itself to provide a cylindrical compound removal device or core; [0030] Figure 12 is a perspective view of the core of Figure 11 sliced into a plurality of disc-shaped removal devices; WO 03/078023 PCT/US03/06922 -6 [0031] Figure 13 is a plan view of a portion of a method of making the removal device embodying the present invention; [0032] Figure 14 is a perspective view of an alternative method of making a removal device embodying the present invention; [0033] Figure 15 is a general diagram showing a continuous manufacturing line for making removal devices embodying the present invention; [0034] Figure 16 is a composite diagram showing some of the different steps in the manufacture of a removal device embodying the present invention. [0035] Figure 17 is a photograph, (taken by a scanning electron microscope and magnified 50x) of the top surface of a removal device embodying the present invention; [0036] Figure 18 is a photograph, (taken by a scanning electron microscope and magnified 25x) providing a side view of a removal device embodying the present invention; [0037] Figure 19 is a photograph, (taken by a scanning electron microscope and magnified 50x) proving a side view of a removal device embodying the present invention; [0038] Figure 20 is another photograph (taken by a scanning electron microscope and magnified 30x) of a removal device embodying the present invention with beads on one surface of the device support being pulled away from the surface; and [0039] Figure 21 is a photograph, (taken by a scanning electron microscope and magnified 25x) of a removal device embodying the present invention with the beads on one surface of the device support being pulled away from the surface. DETAILED DESCRIPTION OF THE DRAWINGS [0040] It will be appreciated that while the present invention is not limited to any particular application or use, the removal devices of the present invention are particularly well suited for use in the treatment of WO 03/078023 PCT/US03/06922 -7 biological fluids, such as blood. Specifically, the removal devices of the present invention are useful in removing compounds from a biological fluid such as blood that has been contacted with the chemical compound in the course of a pathogen inactivation treatment. Accordingly, the present invention is described below in the context of removing pathogen inactivation compounds and/or their derivatives from biological fluids. However, it will be understood that the devices of the present invention may also have uses in other fields where removal of a selected compound from a fluid is desired. [0041] In the pathogen inactivation of biological fluids (such as blood or separated components of blood), the biological fluid to be treated is combined with a pathogen inactivation compound. The compound can be a photoactivation agent that, when contacted with light, acts on the pathogen, or may be a compound that directly acts on the pathogen without any such external stimulus. In some cases, the compound acts by crosslinking the DNA and/or RNA of the pathogen, thereby inactivating it and preventing the pathogen from replicating. Examples of photoactivation agents and/or pathogen inactivation agents include the families of psoralens and acridines. One specific, but non-limiting example of a compound used in light activated pathogen inactivation is 5'- (4-amino-2-oxa) butyl-4, 5', 8 trimethyl psoralen. Details of such pathogen inactivation compounds and treatments are described in U.S. Patent Nos. 5,691,132, 5,593,823 and 6,190,609, all of which are incorporated herein by reference. [0042] Other examples of pathogen inactivation compounds include phthalocyanine derivatives, phenothiazine derivatives (including methylene blue or dimethyl-methylene blue); endogenous and exogeneous photosensitizers such as alloxazines, isoalloxazines (including riboflavin), vitamin Ks, vitamin L, napththoquinones, naphthalenes, naphthols and other compounds disclosed in United States Patent Nos.

WO 03/078023 PCT/US03/06922 -8 6,258,577, 6,268,120 and 6,277,337 which are also incorporated by reference, or "Pen 110" which is made by V.I. Technologies, Inc. (and is also known by its trade name, the Inactine" compound). The above described compounds are particularly useful in the inactivation of blood platelets and plasma. [0043] Other compounds may also be used in the inactivation of pathogens in red blood cells. Examples of such pathogen inactivation compounds include some of the compounds disclosed above and in U.S. Patent No. 6,093,725 and U.S. Application Serial No. 09/539,226 filed March 30, 2000, incorporated herein by reference, which disclose compounds having nucleic acid affinity and containing a mustard group, mustard group equivalent or mustard group intermediate. A preferred compound for red blood cell pathogen inactivation is p-alanine, N-(acridin-9-yl), 2 [bis(2 chloroethyl) amino] ethyl ester. [0044] After treatment with the desired pathogen inactivation agent, the biological fluid is contacted with the removal device, such as a removal device of the present invention, to remove any unreacted pathogen inactivation agent or any of the derivative products from the treatment. [0045] Turning now to the figures, Figure 1 shows a container 10 for holding blood that has been subjected to a pathogen inactivation treatment and that may include unreacted compounds and/or derivatives thereof. Container 10 includes a removal device 20 disposed within container 10 to provide a "batch-type" compound removal system. In a batch-type system, removal device 20 may preferably be placed within a mesh pouch 25 shown in Figure 1 or other liquid permeable pouch. [0046] Container 10 may be part of a larger, disposable blood processing set that includes a first container for holding the biological fluid during the pathogen inactivation treatment, container 10 and a final storage container for receiving the fluid after contact with the WO 03/078023 PCT/US03/06922 -9 compound removal device and for storing the fluid. Alternatively, the processing set may be comprised of the first container and container 10 which holds the removal device and also serves as the final storage container. The processing set may also include a container that holds the pathogen inactivation agent. All of the containers may be integrally connected by plastic tubing. Examples of such blood processing sets are provided in U.S. Patent Application Serial No. 09/325,599, which is incorporated herein by reference in its entirety. [0047] Returning now to Fig.l, the walls of container 10 are made of a thermoplastic material suitable for holding and storing biological fluids and sterilizable by one or more known sterilizing methods such as autoclaving, electron beam and gamma-ray radiation. Examples of such materials include, but are not limited to, polyvinyl chloride plasticized with one or more plasticizers. In one preferred embodiment, container 10 is made of a material that includes polyvinyl chloride plasticized with di ethylhexylphthalate ester and epoxydized oil. Containers made of such material are useful for storing blood platelets and plasma, and are commercially available from Baxter Healthcare Corporation of Deerfield, Illinois under the product code PL-1813. Container 10 may also be made from a plastic material that is a blend of ethylene-vinyl acetate, ultra low density polyethylene and a block copolymer, such as a SEBS-type block copolymer. Plastic containers of this type are particularly well suited for storing blood platelets and are, likewise, available from Baxter Healthcare Corporation of Deerfield, Illinois under product code PL-2410. Container 10 can include a plastic tube 12 that provides a flow path for introducing a biological fluid from another attached container (not shown) and/or removing the fluid from container 10. [0048] As shown in Figures 1-3, in one embodiment, removal device 20 includes a generally flat support 24.

WO 03/078023 PCT/US03/06922 -10 Support 24 may be a solid support, or more preferably, a thin, flexible sheet of a biologically compatible polymeric material, described in more detail below. [0049] Figure 4 shows a preferred support for manufacture of a removal device of the present invention. As shown in Figure 4, support 24 is a flat sheet made of polymeric material such as a non-woven polymeric material. The oppositely facing surfaces 26 and 28 of sheet 24 include a pressure sensitive adhesive or other type of adhesive substance. Alternatively, only one of the surfaces 26 may be coated with adhesive. As further shown in Figure 4, support 24 may be provided with protective backing films 29 and 30 to protect the adhesive prior to use and prior to coating with the sorbent particles. Protective backing films 29 and 30 are peeled off as generally shown in Figure 4, just prior to application of the sorbent beads. [0050] The adhesive used may be any adhesive that is biocompatible with blood and blood products or other biological fluids. Preferably the adhesive should be one that will not leach into the biological fluid and has sufficient tackiness to substantially retain the adsorbent particles on the surface thereof. In a preferred embodiment, the compound removal device of the present invention includes an adhesive coated support sheet made from a polyester, such as Mylar®, or a spun-laced polyester, coated with a biocompatible adhesive such as, but not limited to, a hypoallergenic acrylate adhesive. [0051] Support sheet 24 may have any thickness required or desired, although a relatively thin support is preferred because it allows for better fluid movement of the biological fluid over and around the device, thereby allowing for more complete contact with the biological fluid. In one embodiment, the preferred thickness of the support sheet can be between 1 to 10 mils. The sheets may be provided as individual sheets or, more preferably, WO 03/078023 PCT/US03/06922 -11 provided from a roll of material from which individual sheets can be prepared. Adhesive coated sheets or tapes suitable for use in the present invention will be known to those of skill in the art and are available from the 3M Company of St. Paul, Minnesota, Avery Dennison Corporation of Pasadena, California, and other manufacturers. [0052] In accordance with the present invention, support sheet 24 is coated with a plurality of sorbent beads or particles 22. In one embodiment, sorbent particles 22 are applied to support 24 as a single layer. The particles may be manually applied to the adhesive surface, uniformly distributed and compressed to secure the particles to the adhesive surface. Loose, excess particles may be removed (e.g., by shaking the support sheet). More automated methods for making the compound removal device are described below. [0053] As used herein, "sorbent" is meant to include a material that removes compounds either by adsorption or absorption. Adsorbent particles suitable for use in the compound removal device of the present invention can be any particulate that does not substantially adversely affect the biological activity of a biological composition upon contact. The adsorbent particle can, for example, be made of materials such as activated carbon, hydrophobic resins, hydrophilic resins or ion exchange resins. [0054] In one embodiment the adsorbent particles are activated carbons derived either from natural or synthetic sources. Preferably the activated carbons are derived from synthetic sources. Non-limiting examples of activated carbons include Picactif Medicinal®, which is available from PICA USA Inc. (Columbus, OH), Norit® ROX 0.8, which is available from Norit Americas, Inc. (Atlanta, GA), Ambersorb® 572, which is available from Rohm & Haas (Philadelphia, PA), and G-277®, which is available from PICA (Columbus, OH). [0055] In another embodiment, the particles can be WO 03/078023 PCT/US03/06922 -12 hydrophobic resins. Non-limiting examples of hydrophobic resins include the following polyaromatic adsorbents: Amberlite® adsorbents (e.g., Amberlite® XAD-2, XAD-4, and XAD-16), available from Rohm and Haas (Philadelphia, PA); Amberchrom® adsorbents available from Toso Haas (Toso Hass, Montgomeryville, PA); Diaion®//Sepabeads® Adsorbents (e.g., Diaion® HP20), available from Mitsubishi Chemical America, Inc. (White Plains, NY); Hypersol-Macronet® Sorbent Resins MN-150, MN-200, MN-250, MN-150 and MN-400) available from Purolite (Bala Cynwyd, PA); and Dowex® Adsorbents (e.g., Dowex® XUS-40323, XUS-43493, and XUS-40285), available from Dow Chemical Company (Midland, MI). [0056] Preferred are the synthetic, porous beads made from polyaromatic absorbents including a polystyrene network cross-linked or hyper cross-linked by divinyl benzene bridges. Examples of particularly preferred beads are Dowex® XUS-43493 and Purolite® MN-200 or MN-250, identified above. [0057] These and additional sorbent particles suitable for use with the removal devices of the present invention are further described in U.S. Patent Application serial No. 09/112,400 filed July 8, 1998 and Serial No. 09/112,068 filed July 8, 1998, previously incorporated by reference. [0058] Removal device 20 may be cut or otherwise provided in any shape desired. As shown in Figs. 1-2, removal device may have a generally rectangular shape, having a width almost equal to the width of container 10. As shown in Figs. 5 and 6, removal device may also be provided as a disc with sorbent particles 22 applied to one or both surfaces 26 and 28 of the disc. [0059] As shown in Figure 2, support 24 with sorbent particles 22 carried thereon may be enclosed and sealed inside a liquid permeable pouch 25. Liquid permeable pouch 25 provides an additional protective barrier in the event that the sorbent particles 22 become detached from the support. Mesh pouch 25 may be made of any suitable WO 03/078023 PCT/US03/06922 -13 material, with polyester and nylon being preferred. Materials suitable for use as mesh pouches are available from Tetko of Briarcliff Manor, New York, and sold under the product designation Medifab 07-30-21. The mesh enclosure may be radio frequency sealed around the compound removal device or directly to outer edges of the compound removal device. It will be understood, however, that enclosure of the removal device in a mesh or other liquid permeable pouch is optional because, as described in more detail below, one of the advantages of the present invention is that the sorbent particles remain firmly attached to the adhesive surface (26, 28) of support 24. [0060] In another embodiment, the compound removal device of the present invention may include a plurality of layers to provide either a batch-type device or, more preferably, a flow-through device. In this embodiment, removal device 20 may include alternating layers of support 24 and sorbent particles 22. In one particular embodiment, a layered removal device provides a core for a flow-through device. [0061] Figures 7-10 show an embodiment of the removal device 50 wherein an inner core 40 is made of a plurality of layers of alternating support sheet 24 and sorbent particles 22. The removal device 50 and, more particularly, core 40 shown in Figure 7-10 is particularly well suited for use in a flow-through system. As shown in Figure 7, removal device 50 has an inlet 52 and outlet 54. Inlet 52 and outlet 54 are attached to plastic tubes 56 and 58 that provide flow paths to and from containers 60 and 62 of a blood bag system. [0062] More specifically, as shown in Figure 7, container 60, which may hold the biological fluid that has been treated in a pathogen inactivation treatment and may include unreacted pathogen inactivation compound and/or derivatives thereof, is attached to the inlet port 52 of the compound removal device 50 via plastic tube 56. The WO 03/078023 PCT/US03/06922 -14 outlet port 54 is attached to plastic tube 58 that provides a flow path to a collection container 62 for receiving the biological fluid substantially free of the pathogen inactivation compound or any byproducts. [0063] Removal device 50 includes an inner core 40 provided as a plurality of alternating layers of support sheet 24 and sorbent particles 22. In one embodiment, the core 40 may be provided by taking a sheet 24 of the type shown in Figure 10 and rolling sheet 24 onto itself to provide a "jellyroll" type core 40, as shown in Figure 11. The core 40 may be enclosed in a suitable housing 50 made of a lightweight, biocompatible material, that will be known to those skilled in the art. [0064] Thus, biological fluid enters device 50 through inlet 52. As it passes through device 50, the fluid contacts the sorbent particles 22 of the core 40. Sorbent particles 22 remove the desired compounds from the fluid stream, resulting in a biological fluid substantially free of the compounds. The biological fluid exits through outlet 54 and is collected in container 62. The rate of flow of fluid and the residence time of fluid in contact with particles 22 can be controlled, in part, by how tightly the core has been wound. [0065] Further embodiments of the removal device of the present invention are also possible. For example, using the "jellyroll" core shown in Figure 11, smaller disks 72 of a removal can also be provided. As shown for example in Figure 12, the core 40 can be sliced to provide a plurality of compound removal disks 72. Disks 72 can further be enclosed in a mesh pouch and placed inside a plastic container for holding biological fluid in a batch-type system. [0066] An alternative method of making a removal device in accordance with the present invention is shown in Figure 14. In this embodiment, sorbent particles or beads may be placed on a sheet of liquid permeable mesh material 27.

WO 03/078023 PCT/US03/06922 -15 Interspersed with the sorbent particles or beads 22 are larger particles 23 of hot melt or other similar adhesive. As shown in Figure 14, the particles of hot melt adhesive are generally larger than the maximum diameter of the largest bead 22. A second layer of the liquid permeable mesh material 27 is then placed over the bed of absorbent and adhesive beads. The two sheets of liquid permeable mesh with sorbent and adhesive beads between them are then passed through a heating and compressing element such as heated rolls 25. The gap between the sheet layers is smaller than the smallest of the meltable/fusible adhesive particles but larger or equal to the maximum diameter of the largest sorbent particles. The resulting structure provides two sheets fused to each other through the molten/fused adhesive hot melt particles, thereby immobilizing the smaller particles between them as shown in Figure 14. [0067] Alternatively, instead of using meltable/fusible adhesive particles, a meltable/fusible fiber strip or any other shaped adhesive material may also be used. The edges of the structure can be sealed by means known in the art and also by making the extreme outside edges of the meltable/fusible entities elongated and continuous along the structure. [0068] Regardless of the form, and whether used in a flow-through or batch type system, the compound removal devices of the present invention provide lightweight and easy to manufacture alternatives to currently known removal devices. In addition, the removal devices described above provide efficiencies and economies in manufacturing in that they do not require the sintering or other more complex manufacturing steps. Removal devices of the present invention also maximize exposure of the surface area of the sorbent particles to the biological fluid to be contacted. Removal devices made in accordance with the present invention provide the ability to adsorb/absorb compounds WO 03/078023 PCT/US03/06922 -16 (e.g., pathogen inactivation compounds) as well or better than known removal devices that use significantly more sorbent beads. Finally, removal devices made in accordance with the present invention provide excellent adhesion between the support 24 and sorbent particles 22, thus minimizing the chance of particle shedding. [0069] Figures 17-21 are photographs of the surfaces (26 or 28) and sides of the removal device (of the type shown in Figures 1-3) taken with a scanning electron microscope. Figures 17-21 show some of the unique and superior properties of the removal device. As shown in these Figures, the sorbent particles of the present invention provide a large surface area for exposure of the sorbent to the biological fluid to be contacted. [0070] For example, Figure 17 shows the surface (26 or 28) of a flat sheet removal device made in accordance with a present invention. Because the sorbent particles are attached to the support sheet at the adhesive surface only, there is no adhesive material masking most of the particle surface. [0071] Figures 18 and 19 are side views of a flat sheet compound removal device made in accordance with a present invention, using a flat sheet support, with an adhesive support, and a (single) layer of sorbent particles applied thereon. In Figures 18 and 19, adhesion of the sorbent particles to the flat sheet support is shown. The sorbent particles are attached to the flat sheet support, and more particularly, to the adhesive material on the surface of the flat sheet, in such a way that only a small area of the particles surface is masked from contact with the biological fluid. Thus, the "unmasked" area of the sorbent particles is substantially greater than the "masked" area where the particle is attached to the adhesive surface of the support sheet. [0072] Moreover, as shown in Figures 18 and 19, the removal device of the present invention includes a uniform WO 03/078023 PCT/US03/06922 -17 and single layer of sorbent particles on the device surface. Thus, all the particles are substantially exposed to the biological fluid, and none of the particles are buried in the interior of the device where contact with the biological fluid is less direct. [0073] In addition to providing a substantial amount of exposed surface area for contact, the biological fluid compound removal devices of the present invention are less likely to shed or otherwise lose sorbent particles which can then enter the biological fluid. The strong adhesion between the particles and adhesive on the surface of the support sheet is such that the particles do not become easily dislodged from the support sheet surface. [0074] The strong adhesion of the particles to the support surface is demonstrated and shown in Figures 20-21. Particles adhered to a support surface with pressure sensitive adhesive were contacted at their exposed (unmasked) surfaces with another portion of the adhesive surface. The two surfaces were then pulled apart, so that the beads were pulled away from the support sheet. As shown in Figures 20-21, beads were stretched significantly but did not break off or were not otherwise removed from the support sheet. Figures 20-21 show that the adhesive holding the sorbent particle stretches significantly but does not break off from the support surface. [0075] Thus, compound removal devices of the present invention provide advantages over currently known removal devices. First, they provide a removal device wherein the "unmasked" area of the sorbent particles is substantially greater than the "masked" area where the particle contacts the surface. However, even with such minimal contact between the adhesive of the support sheet and the particles surface, the removal device of the present invention does not substantially shed particles. The ability of the compound removal device to retain most of the particles without shedding is further demonstrated by the following WO03/078023 PCT/US03/06922 -18 examples. [0076] Removal devices in accordance with the present invention may be made individually or, more preferably, as part of a continuous process. Figure 15 is a diagram of a continuous process for manufacturing removal devices of the present invention. Figure 16 is a composite view illustrating some of the different steps shown diagrammatically in Figure 15. As shown in Figure 15, a dispensable roll 100 of the double-sided adhesive tape 102 of the type described above may be provided. The paper is threaded over rollers 112 which advance the tape 102 through a series of processing steps. In one embodiment, the double-sided adhesive tape 102 may be pre-scored and pre-perforated for removal of selected portions of the protective backing film, as described in more detail below and shown, for example, by the broken lines in tape 102 in Figure 16. [0077] For example, pickup mechanism 114 removes a portion of the pre-scored backing film (29 and/or 30) as the belt moves through the system, thereby exposing central portions of both sides (or if desired, one side) of the adhesive surface 26 of tape 102. The paper may be pre scored in such a way that only a film "frame" 138 remains on the tape 102. [0078] Tape 102 is advanced to a reservoir 116 containing suitable particles or beads. As the belt is advanced through the reservoir 116, the exposed portions of adhesive surfaces 26 and 28 are coated with and covered by the particulate or beads 22 in the reservoir 116. Thus, as the portion of the belt exits the reservoir, it has a bead 22 or other particulate coating on both surfaces 26 and 28 of the tape 102. [0079] Figure 13 depicts one example of a reservoir 116 that can be used in the manufacturing line shown in Figures 15 and 16. Reservoir 116 may be generally V-shaped having a narrow inlet slit 140 through which adhesive tape 102 WO 03/078023 PCT/US03/06922 -19 enters the reservoir. Once coated with beads 22 or other particulate, tape 102 exit through the wide mouth 142 of the reservoir. [0080] Returning to Figures 15 and 16, rollers 112 advance tape 102 through the system whereby bead coated surfaces 26 and 28 are contacted with brushes 118. Brushes 118 remove excess loose beads or particulate from the tape 102. Next, if desired, the bead-coated tape 102 moves through a set of rollers 122 that compress the beads onto the adhesive. As tape 102 continues through the system, the remaining frame is removed by paper pickup device 124, thus removing the "frame" 138 of backing film, and providing and exposing an "adhesive coated frame" 142 around the bead-coated surfaces 24 and 26 of the tape 102. [0081] If a mesh covering is desired for the removal device, sheets of mesh 144 can be applied over both surfaces of the removal device. In particular, sheets of mesh 144 can be applied from dispensing rollers 130 over each of the bead-coated surfaces 24 and 26. The bead coated removal device, sandwiched between two sheets of the mesh enclosure, may now be sealed by radio frequency or other known sealing techniques, depicted generally at 146 so as to completely enclose the removal device within the mesh pouch. Alternatively, the mesh sheets may adhere directly to the adhesive coated frame 142, with or without additional sealing. [0082] Finally, tape 102 may be cut along the seal line to the desired size at the end of the process to provide a removal device. Alternatively, if the removal device is to be used as a core 40 in a flow-through device 50, the bead coated tape prepared in the manner described above can be "jelly-rolled" and placed in a housing 50 as shown and described above. [0083] The foregoing description has been offered for illustrative purposes only, and it will be appreciated that various modifications of the embodiments and methods WO 03/078023 PCT/US03/06922 -20 described herein are possible in accordance with the scope of the present invention.

Claims

1. A device for removing a compound from a fluid comprising: at least one support surface; a plurality of sorptive particles carried by said support surface, said particles having a masked area wherein said particles contact said support surface and an unmasked area not in contact with said support surface.

2. The device of Claim 1 wherein said support surface comprises a flexible sheet of a polymeric material.

3. The device of Claim 1 wherein said sorptive particles comprise polystyrene copolymerized with divinylbenzene.

4. The device of Claim 1 further comprising a liquid permeable pouch containing said support surface with said sorptive particles carried thereby.

5. The device of Claim 1 wherein said support surface comprises a thin, flexible sheet having a pressure sensitive adhesive applied on said support surface.

6. The device of Claim 1 further comprising a plurality of meltable adhesive particles carried by said support surface and dispersed within or among said plurality of sorptive particles.

7. The device of Claim 1 further comprising first and second support surfaces with a plurality of sorptive particles carried by said first and second surfaces.

8. A device for removing a compound from a fluid comprising: a flexible sheet support having first and second oppositely facing sides; a plurality of sorptive particles attached to said first and second sides, said particles having a masked area where said particles contact said support and an unmasked area not in contact with said support.

9. The device of Claim 8 wherein said support surface comprises a flexible sheet of a polymeric material. WO 03/078023 PCT/US03/06922 -22

10. The device of Claim 8 wherein said sorptive particles comprise polystyrene copolymerized with divinylbenzene.

11. The device of Claim 8 further comprising a liquid permeable pouch containing said support surface with said sorptive particles carried thereby.

12. The device of Claim 8 wherein said support surface comprises a thin, flexible sheet having a pressure sensitive adhesive disposed on said support surface.

13. The device of Claim 8 further comprising a plurality of hot melt particles carried by said support surface and dispersed within or among said plurality of sorptive particles.

14. A sorptive core for use with a compound removal device comprising: a plurality of layers, each layer comprising a sheet having first and second sides with a plurality of sorptive particles attached to at least one of said sides, to provide alternating portions of said sheets and particles.

15. The core of Claim 14 wherein said sheet comprises a adhesive material applied thereto to attach said sorptive particles to said sheet.

16. The core of Claim 14 wherein said plurality of layers comprises a sheet having first and second sides and a plurality of sorptive particles attached to at least one of said sheets wherein said sheet is rolled to provide a generally cylindrical core having a first end and a second end.

17. The device of Claim 16 wherein said core is associated with a fluid inlet at said first core end and a fluid outlet at said second core end.

18. The core of Claim 14 wherein said sorptive particles comprise polystyrene copolymerized with divinylbenzene.

19. The core of Claim 14 wherein said sheet comprises a pressure sensitive adhesive applied thereon. WO 03/078023 PCT/US03/06922 -23

20. A method for making a device for removing a compound from a fluid comprising: providing a flexible support sheet having first and second oppositely facing sides, wherein at least one of said sides comprises an adhesive surface; and contacting said adhesive surface with a plurality of sorptive particles.

21. The method of Claim 20 wherein said support sheet comprises a protective cover over said adhesive surface, said method further comprising removing said cover prior to said contacting.

22. The method of Claim 20 further comprising removing excess beads or particles from said surface after contacting.

23. The method of Claim 20 wherein at least a portion of said protective cover is selectively removed to expose only a portion of said adhesive surface.

24. The method of Claim 20 further comprising removing the remaining portion of said protective cover from said adhesive surface after said contacting.

25. The method of Claim 20 further comprising enclosing said flexible support sheet with sorptive particles carried thereon into a mesh enclosure.

26. The method of Claim 20 further comprising sealing said enclosure along the periphery to enclose said support surface with said particles disposed thereon.

27. The method of Claim 20 wherein said particles comprise polystyrene copolymerized with divinylbenzene.

28. The method of Claim 20 comprising contacting said support surface with said sorptive particles by introducing said support surface into a container filled with said sorptive particles and removing said support surface from said container.

29. The method of Claim 20 comprising providing a plurality of flexible support sheets on a conveyor. WO 03/078023 PCT/US03/06922 -24

30. The method of Claim 20 wherein said adhesive surface comprises a pressure sensitive adhesive applied on said support surface.