SELECTIVE MEMBRANE/SORPTION TECHNIQUES FOR SALVAGING BLOOD

Abstract: Methods and apparatuses for salvaging blood from a patient are disclosed. A blood salvaging circuit (140) coupled to a cardiopulmonary bypass circuit (144) includes a hemoconcentrator (152) and a sorbent-containing plasma separator. A combination device (142) for salvaging blood includes a closed plasma chamber (172) containing a plasma chamber solution (176), a hollow fiber plasma-separating membrane (156) for receiving blood and permitting plasma to be transported therethrough into the plasma chamber solution (176) and for refiltering the treated plasma back into the blood salvaging circuit (140), a selective sorbent (180) for contacting the selected solute in the plasma and binding the selected solute and an ultrafiltration membrane (184) for removing water, fluids and low molecular weight components from the plasma.

Description: SELECTIVE MEMBRANE/SORFTTON TECHNIQUES FOR SALVAGING BLOOD CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 60/013,135, filed March 8, 1996. BACKGROUND OF THE INVENTION This invention relates to a system and method for salvaging or recovering blood to reduce net blood loss during surgery or other medical procedure and selectively removing solutes from plasma. More particularly, the invention relates to a system and method for removing excess water and/or fluid from whole blood or plasma and selectively removing solutes, such as drugs (e.g. heparin), autoantibodies, toxins, antigens, plasma components, and lipids (e.g. cholesterol) from plasma such that the treated blood can be administered directly to the patient or saved for later administration. A patient undergoing major cardiac surgery with cardiopulmonary bypass (CPB) can lose a significant amount of blood. If the blood loss is profuse, the patient may require the administration of homologous blood products. Homologous blood products can sometimes be in short supply and may carry blood-borne padiogens. To reduce the amount of blood loss during surgery and thus the need for administration of homologous blood products, several methods of intraoperative blood salvage or autotransfusion have been tried. These methods include administration of drugs (e.g. aprotinin, e-amino caproic acid), hemoconcentration, modified ultrafiltration, cell washing, autologous predonation of blood for perioperative reinfusion, and autotransfusion of processed shed blood. J. Boldt et al., Blood Conservation in Cardiac Operations — Cell Separation Versus Hemofiltration, 97 J. Thorac. Cardiovasc. Surg. 832 (1989); Y. Nakamura et al. , Comparative Study of Cell Saver and Ultrafiltration Nontransfusion in Cardiac Surgery, 49 Ann. Thorac. Surg. 973 (1990); J. Boldt et al., Six Different Hemofiltration Devices for Blood Conservation in Cardiac Surgery, 51 Ann. Thorac. Surg. 747 (1991); D. Tixier et al., Blood Saving in Cardiac Surgery: Simple Approach and Tendencies, 6 Perfusion 265 (1991); Y. Iu et al., Maximizing Blood Conservation in Cardiac Surgery, Perfusion Life 14 (July 1994); R. Breyer et al., A Comparison of Cell Saver Versus Ultrafilter During Coronary Artery Bypass Operations, 90 J. Thorac. Cardiovasc. Surg. 736 (1985); P. Page, Ultrafiltration Versus Cell Washing for Blood Concentration, 22 J. Extra-Corp. Tech. 142 (1990); H. Johnson et al., Comparative Analysis of Recovery of Cardiopulmonary Bypass Residual Blood: Cell Saver vs. Hemoconcentrator, 26 J. Extra-Corp. Tech. 194 (1994); J. Morris & Y. Tan, Autotransfusion: Is There a Benefit in a Current Practice of Aggressive Blood Conservation?, 58 Ann. Thorac. Surg. 502 (1994). Of these techniques, hemoconcentration and cell washing are among d e most commonly encountered. Hemoconcentration or ultrafiltration extracts water and low molecular weight solutes from the plasma fraction of whole blood. Plasma proteins, including proteins involved in me coagulation cascade, remain relatively intact. Hemoconcentrators are generally small, compact, cost-effective, and can be added to an existing CPB circuit without major modifications. A disadvantage of hemoconcentration is that debris cannot be removed, thus shed blood collected during surgery cannot be processed through a hemoconcentrator unless it has first been filtered, i.e. through a cardiotomy reservoir. Moreover, hemoconcentration does not remove heparin from the blood, thus even though water has been removed, the blood remains fully heparinized. Another disadvantage is that plasma-free hemoglobin, which results from hemolysis and is known to be toxic to the kidneys, is not effectively removed by hemoconcentration filters. Cell washing is a method of blood concentration wherein whole blood is subjected to centrifugation while being rinsed with a saline solution. Cell washing removes debris, plasma-free hemoglobin, and heparin, thus the method can be used on shed blood as well as blood remaining in the CPB circuit and cardiotomy reservoir. A major disadvantage of cell washing is diat all of die plasma proteins, including coagulation proteins, are discarded. Platelets are lost as well. Further, cell washing requires that a separate system, including a centrifuge, be dedicated for such a procedure. Therefore, the process of cell washing is more expensive than hemoconcentration. Moreover, since coagulation proteins are removed in me process, it is sometimes necessary to administer replacement factors after cell washing. Shettigar et al., U.S. Patent No. 5,211,850, describes a plasma membrane sorbent system for removal of solutes from blood. The system comprises a bundle of U-shaped hollow fibers immersed in an electrolyte solution with a sorbent contained in a closed plasma chamber. As blood flows through die entry arm, plasma filtration into the plasma chamber occurs. Solutes in the plasma are selectively depleted in me plasma chamber through binding to me sorbents. The purified plasma men reenters me membrane by reverse filtration. S. Ash et al., U.S. Patent No. 4,071,444, discloses a portable "flat plate" reactor for use as an artificial kidney. The device comprises a sealed outer casing that is divided internally by a series of flexible membranes into chambers adapted to receive blood and other chambers adapted to receive a solution containing water, activated charcoal, zirconium phosphate, zirconium oxide and urease or otiier sorbents for absorbing the urea and creatinine drawn through me membrane from me blood. S. Ash, U.S. Patent No. 4,348,283, describes a dialyzer for use as an artificial kidney or extracorporeal mass transfer device. The device comprises a plurality of dialyzer units, each unit comprising a pair of semipermeable membranes spaced apart by a gasket such mat a blood chamber is formed between the membranes. Spacers are used to separate the dialyzer units and support the membranes. The spaces between me dialyzer units form dialysis chambers, which contain a suspension of sorbents, such as activated charcoal, calcium-sodium loaded zeolites, and/or urease. S. Ash, U.S. Patent No. 4,581,141, teaches a dialysis material and method for removing uremic substances, wherein me dialysis material comprises an aqueous slurry containing charcoal, a highly calcium-loaded zeolite cation exchanger, a purified urease, a suspending agent such as methylcellulose, and an aliphatic carboxylic acid resin in the acid form. S. Ash, U.S. Patent No. 4,661,246, discloses a dialysis instrument with a pump on the dialysate side of me instrument for moving blood through me instrument. The instrument contains a sorbent column for purification of the dialysate, die sorbent column containing activated charcoal, immobilized urease, zirconium phosphate cation exchanger, and zirconium oxide anion exchanger. S. Ash, U.S. Patent No. 5,277,820, describes a device and method for extracorporeal treatment of blood for the removal of toxins. A sorbent suspension is used for removing such toxins wherein the sorbent comprises a powdered surface adsorptive agent such as activated charcoal, physiological electrolytes, a cation exchanger for removing ammonium ions and me like, and macromolecular flow inducing agents such as polyoxyalkylene derivatives of propylene glycol or polyvinylpyrrolidone. Cisplatin and methotrexate could be removed from the blood by this method. These apparatuses and methods all lack me ability to be used for bom hemoconcentration and removal of selected solutes from the blood. In view of me foregoing, it will be appreciated mat development of a system and process that removes excess water and/or fluid from whole blood or plasma, conserves plasma proteins including coagulation proteins, reduces and/or removes plasma-free hemoglobin and heparin and other targeted molecules, is cost effective, and is easily used and incorporated into an existing CPB circuit or in parallel witii a CPB circuit, in contrast to the prior art where expensive, stand-alone devices are used and perhaps require additional personnel to operative diem, would be a significant advancement in me art. BRIEF SUMMARY OF THE INVENTION It is an object of the present invention to provide a system and method for conserving blood during cardiac surgery or other medical procedure where blood loss can be copious. It is also an object of me invention to provide a system and method for removing excess water and/or fluid from whole blood or plasma, wherein plasma proteins, including coagulation proteins, can be conserved. It is another object of the invention to provide a system and method for conserving blood during cardiac surgery or other medical procedure where blood loss can be copious wherein selected solutes, such as heparin, plasma free hemoglobin, and selected proteins or hormones that have been activated, are reduced or removed. It is still anomer object of die invention to provide a system and method for conserving blood during cardiac surgery wherein such system and memod are cost effective, easy to use, and can be incorporated into an existing CPB circuit. These and other objects can be accomplished by providing a system for salvaging blood from a patient for the selective removal of a targeted solute in the blood and me removal of water, fluids, and low molecular weight solutes comprising: (a) a hemoconcentrator comprising a porous ultrafiltration membrane having a selected molecular weight cut-off for retaining components selected from the group consisting of cells and solutes wim a molecular weight greater than the cut-off and for allowing water, fluids, and solutes wim a molecular weight less man die cut-off to be removed from blood or plasma; and (b) a first solute removal device for selectively removing the targeted solute from blood by means of convective and diffusive transport of plasma from the blood across a hollow fiber plasma-separating membrane into a plasma chamber where the selective removal of the targeted solute from non-targeted solutes using a sorbent is accomplished followed by me subsequent transport of the non-targeted solutes across the plasma-separating membrane back into me blood, comprising (i) a closed plasma chamber configured for being filled with a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in the plasma chamber solution under relatively uniform pressure; (ii) die hollow fiber plasma-separating membrane, wherein me plasma-separating membrane has an inlet arm and an outlet arm and is configured for being immersed in the plasma chamber solution in the closed plasma chamber; (iii) at least one sorbent having an affinity for binding die targeted solute, wherein die sorbent is contained in die closed plasma chamber; (iv) means for securing die inlet arm and outlet arm of the plasma-separating membrane in the plasma chamber and closing the chamber to maintain relatively uniform plasma chamber solution pressure; and (v) means for circulating the blood into me inlet arm, through the plasma-separating membrane, and out dirough d e outlet arm; and (c) means for coupling the hemoconcentrator to the first solute removal device to permit liquid communication therebetween and for coupling die hemoncentrator and die first solute removal device to the patient to permit blood to be received from and returned to the patient. Preferably, the porous ultrafiltration membrane of the hemoconcentrator comprises a plurality of hollow fibers having a molecular weight cut-off in the range of about 10,000 to 100,000. Preferred materials include polyacrylonitrile, polysulfone, polynediylmediacrylate, cellulose acetate, cellulose diacetate, and cellulose triacetate. Preferably, the hollow fiber plasma-separating membrane comprises a bundle of parallel hollow fibers constructed of a blood-compatible material having a suitable pore size to allow passage of plasma into the plasma chamber solution while retaining blood cells and platelets from the blood wimin die hollow fibers. It is preferred diat pore sizes in die plasma-separating membrane range between about 0.01 μm to 1.0 μm and the plasma-separating membrane is made from a material selected from the group consisting of polypropylene, cellulose diacetate, polycarbonate, polyvinylchloride, polyvinylalcohol, polymethylmethacrylate, polyethylene, polysulfone, and polyethylenevinylalcohol . The sorbent should be of a size and configuration such that said sorbent is not permeable to the plasma-separating membrane. The sorbent comprises a ligand immobilized on a substrate wherein the ligand is preferably a member selected from the group consisting of enzymes, living tissue, fragments of tissue, cells, antibodies, peptides, macromolecules, nucleic acids, lectins, carbohydrates, and chelating agents. In preferred embodiments, me sorbent has affinity for heparin and me substrate is agarose. In an especially preferred embodiment, the sorbent is poly-L-ly sine-coupled agarose. The hemoconcentrator and solute removal device can be configured for simultaneous hemoconcentration and removal of me targeted solute or for sequential hemoconcentration and removal of the targeted solute. The system can also be configured such d at hemoconcentration, i.e. removal of water, fluids, and low molecular weight solutes, is carried out in me blood or in the plasma. To remove water, fluids, and low molecular weight solutes from the plasma, the porous ultrafiltration membrane can be placed in the plasma chamber of the solute removal device or a second solute removal device can be added to d e system, wherein die hemoconcentrator is placed to interconnect the two plasma chambers. Thus, an apparatus for selectively removing a targeted solute from blood by binding the targeted solute to an affinity sorbent and removing water, fluids, and low molecular weight solutes by ultrafiltration comprises: (a) a closed plasma chamber configured for being filled widi a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in the plasma chamber solution under relatively uniform pressure; (b) a hollow fiber plasma-separating membrane having an inlet arm and an outlet arm and configured for being immersed in the plasma chamber solution in the closed plasma chamber; (c) at least one sorbent having an affinity for binding the targeted solute, wherein die sorbent is contained in me closed plasma chamber; (d) means for securing the inlet arm and outlet arm of the plasma- separating membrane in die plasma chamber and closing the chamber to maintain relatively uniform plasma chamber solution pressure; and (e) a porous ultrafiltration membrane disposed in die closed plasma chamber and configured for being immersed in die plasma chamber solution, the ultrafiltration membrane having a selected molecular weight cut-off for allowing water, fluids, and solutes with a molecular weight lower than the cut- off to pass theretlirough and for retaining solutes with a molecular weight greater than me cut-off and means for withdrawing me water, fluids, and solutes that pass dirough die ultrafiltration membrane; and (f) means for circulating the blood into die inlet arm such that plasma, including water, fluids, and low molecular weight solutes dierein, is transported from the blood across me plasma-separating membrane by convective and diffusive transport into the plasma chamber solution where the selective removal of the targeted solute from non-targeted solutes using die affinity sorbent is accomplished followed by d e subsequent transport of me non-targeted solutes across the membrane back into the blood and out dirough the outlet arm. Moreover, a system for salvaging blood from a patient for the selective removal of a targeted solute in the blood and die removal of water, fluids, and low molecular weight solutes comprises: (a) a hemoconcentrator comprising an inlet port, an ouUet port, and a porous ultrafiltration membrane having a selected molecular weight cut-off for retaining components selected from e group consisting of cells and solutes wid a molecular weight greater than the cut-off and for allowing water, fluids, and solutes with a molecular weight less than me cut-off to be removed from blood or plasma; and (b) first and second solute removal devices for selectively removing the targeted solute from blood by means of convective and diffusive transport of plasma from the blood across a hollow fiber plasma-separating membrane into a plasma chamber where the selective removal of the targeted solute from non- targeted solutes using a sorbent is accomplished followed by die subsequent transport of die non-targeted solutes across the plasma-separating membrane back into the blood, each first and second solute removal device comprising (i) a closed plasma chamber configured for being filled wim a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in die plasma chamber solution under relatively uniform pressure; (ii) the hollow fiber plasma-separating membrane, wherein the plasma-separating membrane has an inlet arm and an outlet arm and is configured for being immersed in die plasma chamber solution in the closed plasma chamber; (iii) at least one sorbent having an affinity for binding d e targeted solute, wherein the sorbent is contained in die closed plasma chamber; (iv) means for securing me inlet arm and outlet arm of the plasma-separating membrane in the plasma chamber and closing me chamber to maintain relatively uniform plasma chamber solution pressure; and (v) means for circulating the blood into me inlet arm, through d e plasma-separating membrane, and out dirough the oudet arm; (c) means for coupling the plasma chamber of the first solute removal device to die inlet port of me hemoconcentrator and means for coupling the outlet port of the hemoconcentrator to me plasma chamber of the second solute removal device such mat plasma can flow from the first solute removal device dirough die hemoconcentrator to the second solute removal device such tiiat water, fluids, and low molecular weight solutes can be removed from the plasma by ultrafiltration, and means for coupling the outlet arm of the first solute removal device to die inlet arm of the second solute removal device such diat blood can flow therebetween; and (d) means for coupling the first and second solute removal devices to the patient to permit blood to be received from and returned to die patient. A method of selectively removing a targeted solute and water, fluids, and low molecular weight solutes from blood comprises: (a) providing a system comprising: (1) a hemoconcentrator comprising a porous ultrafiltration membrane having a selected molecular weight cut-off for retaining components selected from the group consisting of cells and solutes with a molecular weight greater than the cut-off and for allowing water, fluids, and solutes wid a molecular weight less than the cut-off to be removed from blood or plasma; and (2) a first solute removal device for selectively removing the targeted solute from blood by means of convective and diffusive transport of plasma from the blood across a hollow fiber plasma- separating membrane into a plasma chamber where the selective removal of the targeted solute from non-targeted solutes using a sorbent is accomplished followed by me subsequent transport of the non-targeted solutes across die plasma-separating membrane back into the blood, comprising (i) a closed plasma chamber configured for being filled widi a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in the plasma chamber solution under relatively uniform pressure; (ii) the hollow fiber plasma-separating membrane, wherein the plasma-separating membrane has an inlet arm and an outlet arm and is configured for being immersed in me plasma chamber solution in the closed plasma chamber; (iii) at least one sorbent having an affinity for binding the targeted solute, wherein the sorbent is contained in the closed plasma chamber; (iv) means for securing the inlet arm and outlet arm of the plasma-separating membrane in the plasma chamber and closing die chamber to maintain relatively uniform plasma chamber solution pressure; and (v) means for circulating the blood into me inlet arm, through the plasma-separating membrane, and out dirough the outlet arm; and (3) means for coupling the hemoconcentrator to the first solute removal device to permit liquid communication therebetween and for coupling me hemoncentrator and die first solute removal device to die patient to permit blood to be received from and returned to die patient; (b) directing the blood from a source into the inlet arm by the means for circulating the blood, dirough the plasma-separating membrane and out die outlet arm at a volume and a velocity diat permits convective and diffusive transport of plasma from the blood across me plasma-separating membrane along the inlet arm of the plasma-separating membrane into the plasma chamber solution; (c) causing the plasma in the plasma chamber solution to come into contact with die sorbent such that me targeted solute is selectively bound to the sorbent; (d) causing the non-targeted solutes to pass by diffusive and convective transport from the plasma chamber solution across the plasma- separating membrane into the blood retained by die plasma-separating membrane and out of die device; (e) causing die blood or plasma to pass through the hemoconcentrator such that water, fluids, and solutes widi a molecular weight less than the cut-off pass dirough me porous ultrafiltration membrane and are wididrawn from the blood or plasma, and me ultrafiltration membrane retains cells and solutes widi a molecular weight greater than die cut-off in the blood or plasma. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS FIG. 1 shows a schematic diagram of a CPB circuit according to die prior art. FIG. 2 shows a schematic diagram of an illustrative embodiment of a blood salvage circuit according to die present invention comprising a hemoconcentrator and a solute removal device. FIG. 3 shows a schematic diagram of a solute removal device according to die present invention. FIG. 4 shows a schematic diagram of another illustrative embodiment of a blood salvage circuit according to die present invention. FIG. 5 shows a schematic diagram of still another illustrative embodiment of a blood salvage circuit according to die present invention. FIG. 6 shows a schematic diagram of a combined device according to d e present invention comprising a plasma separator with sorbent for removing selected solutes and an ultrafiltration membrane for hemoconcentration. DETAILED DESCRIPTION Before the present system and method for salvaging or recovering autologous blood are disclosed and described, it is to be understood diat mis invention is not limited to die particular embodiments, process steps, and materials disclosed herein as such embodiments, process steps, and materials may vary somewhat. It is also to be understood diat die terminology employed herein is used for die purpose of describing particular embodiments only and is not intended to be limiting since the scope of die present invention will be limited only by die appended claims and equivalents thereof. It must be noted diat, as used in diis specification and me appended claims, the singular forms "a," "an," and "die" include plural referents unless the context clearly dictates odierwise. For example, reference to "a solute" includes reference to two or more of such solutes, and reference to a device comprising "a sorbent" includes reference to a device comprising one or more or such sorbents. In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below. As used herein, "patient" refers to a human or a warm-blooded animal. As used herein, "patient blood" refers to blood taken directly from a patient, such as blood collected by predonation for storage and eventual administration to the patient. As used herein, "circuit blood" refers to blood diat is circulated dirough the CPB circuit. Circuit blood is typically given back to the patient before die end of surgery or shortly mereafter. As used herein, "shed blood" refers to blood diat is lost during surgery. Shed blood is aspirated from the body and stored in a cardiotomy reservoir. As used herein, "peptide" means peptides of any lengdi and includes proteins. Blood consists of cellular and non-cellular fractions, or, alternatively, of formed and non-formed elements. As used herein, "plasma" means the non- cellular fraction or non-formed elements of blood. In other words, plasma means the portion of blood exclusive of die cellular fraction or formed elements thereof. As used herein, "sorbent" means a ligand coupled to a substrate. Sorbents can be in any usable form of sufficient size that me sorbent is not permeable to the plasma-separating membrane of the solute removal device, i.e. does not enter die blood. For example, sorbents can be in particulate form, such as beads, spheres, or the like. Sorbents can also be present as filaments, strands, sheets, or films. The form is not important as long as there is adequate opportunity for die circulation of plasma and contact between the sorbent and the plasma. Suitable substrates include biocompatible polymers, such as agarose, polyacrylamide, nylon, nitrocellulose, polystyrene, and die like. The substrate should have functional groups to which me ligand can be attached according to principles and materials well known in the art. Suitable ligands include antibodies, peptides, enzymes, nucleic acids, lectins, carbohydrates, chelating agents, macromolecular ligands, and die like. As used herein, "plasma chamber solution" means the solution contained in the plasma chamber. At the beginning of a separation procedure, die initial solution will typically comprise water or an electrolyte, i.e. saline, solution containing sorbents and other selected materials. As the various plasma components enter the plasma chamber by convection or diffusion from the hollow fiber plasma-separating membrane, equilibration will take place such diat, except for the targeted components bound to me sorbent in the plasma chamber, the concentration of plasma components in the blood inside me lumens of the hollow fibers will be die same as the concentration of the plasma components in the plasma chamber. Hence, the makeup of me plasma chamber solution can vary during the removal process, but functionally the action composition is not critical. Referring to FIG. 1, mere is shown a schematic representation of a CPB circuit 4. Venous blood is removed from the patient 6 and conducted by gravity flow to a venous or CPB circuit blood reservoir 8. Blood is pumped out of die CPB reservoir 8 by a pump 12. This blood optionally can be circulated dirough a hemoconcentrator 16 for removing water, fluids, and low molecular weight molecules. Blood diat has passed dirough die hemoconcentrator is returned to die venous reservoir 8. Blood can also be pumped dirough an oxygenator 20 for supplying oxygen to the blood. The oxygenator 20 is coupled to a source of oxygen 24 dirough an oxygen line 28. The oxygenator 20 is coupled to an arterial filter 32 for filtering the oxygenated blood before it is recirculated into die CPB circuit reservoir 8 or returned to the patient 6. Shed blood is removed from the patient 6 by means of a pump 36 and stored in a cardiotomy reservoir 40, where the shed blood is filtered. The cardiotomy reservoir 40 is coupled to die CPB circuit reservoir 8 such that filtered shed blood can selectively be mixed with CPB circuit blood. FIG. 2 shows an embodiment of the present invention comprising a CPB circuit blood reservoir or cardiotomy reservoir or patient 48 coupled to a blood salvage circuit 56. The blood salvage circuit comprises a pump 60 for pumping the blood out of die reservoir 48 and moving it through me blood salvage circuit. The blood salvage circuit further comprises a hemoconcentrator 88 for removing water and low molecular weight solutes from the blood and a solute removal device 64 for separating plasma from the blood and contacting me separated plasma with a specific sorbent for removing a selected solute. Such a device is described in U.S. Patent No. 5,211 ,850, which is hereby incorporated by reference, and is shown in FIG. 3. Line 50 couples the blood reservoir 48 to die hemoconcentrator 88, line 52 couples the hemoconcentrator to the solute removal device, and line 54 couples die solute removal device to die blood reservoir 48. Referring now to FIG. 3, the solute removal device 64 comprises a bundle of hollow fibers mat make up a hollow fiber plasma-separating membrane 66. Each hollow fiber has a central lumen through which die whole blood passes from the inlet arm 68 to the outlet arm 72 of the sorbent removal device. Each hollow fiber membrane has a series of pores or openings dirough which plasma and plasma components, toxins, drugs, or odier solutes having diameters smaller than the pores can pass into a surrounding plasma chamber solution 76 containing a sorbent 80. The hollow fiber plasma-separating membrane 66, plasma chamber solution 76, and sorbent 80 are contained in a housing 84. The housing is closed by fixed potting material 85 and 86. The inlet arm of the plasma-separating membrane is coupled to an inlet line 87, and die oudet arm is coupled to an outlet line 89. Optionally, a plasma port 82 in the housing permits access to the plasma chamber for removing plasma therefrom, for making pressure measurements, adding sorbent or plasma chamber solution, or me like. The plasma may contain various sugars, proteins, hormones, antibodies, fats, bile salts, toxins, electrolytes, and die like, as well as other substances diat may have been administered for various purposes. Heparin, for example, is added to die patient for its anticoagulation properties, but is desirably removed or inactivated at the end of CPB. When heparin and odier small solutes exit the membranes through the pores by convection (pressure gradients) or diffusion, diey enter into the plasma chamber solution 76 containing sorbent particles 80 that have a specificity for binding heparin or other selected solutes. The hollow fiber plasma-separating membrane can be made of any blood compatible material having suitable pore size to allow passage of selected solute materials into the plasma chamber, even those of high molecular weight, and yet retain the blood cells and platelets in die lumen of the hollow fiber. Pore sizes in me membrane are relatively large, with sizes ranging between about 0.01 μm to 1.0 μm being suitable, with pore sizes of about 0.1 μm to 0.8 μm being preferred and pore sizes of about 0.4 to 0.75 μm most preferred. Exemplary of suitable fiber materials are polypropylene, cellulose diacetate, polycarbonate, polyvinylchloride, polyvinylalcohol, polymethylmethacrylate, polyediylene, polyethylenevinylalcohol, polysulfone, and die like. The hollow fiber plasma-separating membrane dimensions (hollow fiber lumen diameter, length of each hollow fiber, and d e number of fibers) and die blood flow rate dirough die fiber have to be optimized based on die art of membrane plasma separation. It is well known in the art of membrane plasma separation that die plasma separation rate is directly proportional to the blood shear rate and die transmembrane pressure. Damage to the blood cells, however, may occur if the transmembrane pressure is increased beyond a particular limit. Also, blood cells are susceptible to high shear rate. For a given blood flow rate and total membrane surface area, transmembrane pressure increases with die increase in hollow fiber lengdi and widi me decrease in lumen size. Shear rate also increases with the decrease in lumen size. The above-mentioned factors may be considered in arriving at the optimum size of the hollow fiber membrane. The removal rates of solutes from the blood depend on die plasma separation rate, the amount (surface area, etc.), affinity of sorbents, and the extent of plasma-sorbent interaction. Hollow fibers of the plasma-separating membrane having inside diameters of between about 150 μm and 500 μm and wall diicknesses of between about 50 μm to 400 μm are typical. The internal surface area of a typical plasma-separating membrane can be between about 0.1 and 5.0 m 2 , and die volume of the plasma chamber can be between about 50 and 1000 ml. The length of die plasma-separating membrane from e inlet port to the exit port should be between about 10 and 100 cm, with lengdis of about 20 to 25 cm being preferred. Flow rates of blood dirough die plasma-separating membrane can vary from about 50 to 3000 ml/min. The plasma chamber should be sized to hold an adequate amount of sorbent materials to adsorb die unwanted solutes, such as heparin. This may vary depending on die medical procedure for which die blood salvage system is being used and die amount of heparin or other material to be removed and me nature of the sorbent material. An illustrative commercial device according to FIG. 3 is a heparin removal device (HRD, Research Medical Inc., Midvale, UT). This unit is a disposable hollow fiber membrane-type plasma separator consisting of a microporous polypropylene hollow fiber bundle mounted in polyurethane exit ports and a polystyrene plastic housing. Blood enters the fiber bundle dirough die blood inlet port, passes dirough d e hollow fiber lumens in which a positive transmembrane pressure allows plasma to pass through the porous hollow fiber membrane along its entire length into the plastic housing where it contacts the sorbent. Solutes in the plasma with an affinity for the sorbent bind to e sorbent and are immobilized. The plasma with a reduced concentration of die selected solute can dien be removed from the plasma chamber through the plasma port or can reenter the hollow fiber membrane by refiltration for transport out die device dirough die outiet port. Prior to use, the plasma chamber is prefilled widi plasma chamber solution containing sufficient sorbent particles to bind die plasma component to be separated. The sorbent can be placed in the plasma chamber prior to, simultaneously with, or after filling the plasma chamber with d e plasma chamber solution. Such unit is suitable for use as a simultaneous plasma purification and reinfusion system having the above-described advantages. The removal of heparin from an extracorporeal circuit is a primary objective of the invention. The binding of heparin to a solid substrate by affinity adsorption techniques is documented in the art. E.g., Mohammad et al. , Quantitative Removal of Heparin from Plasma and Odier Aqueous Solutions by Affinity Adsorption on Poly(L)lysine Sepharose 4B, 20 Thrombosis Res. 599-609 (1980). Poly(L)lysine-coupled agarose beads are one form of preferred sorbent. The plasma separator device is applicable to any plasma sorbent system where separation, interaction, and recombination takes place. Typical medical procedures where the blood is heparinized include cardiopulmonary bypass, hemodialysis, angioplastic procedures, plasmapheresis, autotransfusion, and hemoconcentration. Exemplary of other potential applications of die system are removal of autoantibodies using sorbents such as immobilized protein A; removal of circulating toxins and tumor antigens using sorbents such as immobilized monoclonal antibodies and specific immobilized ligands; removal of protein-bound toxins and drugs (e.g., in die case of a drug overdose); procedures using live cells in the plasma chamber in the place of sorbents such as islet cells or liver tissue fragments for the treatment of diabetes, hepatocytes for die treatment of liver failure and me like; selective removal of plasma components using immobilized enzymes as sorbents; and removal of cholesterol (low density lipoproteins, LDL) using sorbents specific to LDL. While not shown in FIG. 2, the hemoconcentrator 88 can be placed in circuit 56 eidier upstream or downstream of the solute removal device 64. The hemoconcentrator 88 is preferably of a type already known in the art for removing water, fluids, and low molecular weight molecules from blood by ultrafiltration. A preferred hemoconcentrator (FIG. 2) comprises a bundle of hollow fiber ultrafiltration membranes 100 in a housing 104 mat defines a chamber in which the hollow fibers are disposed. Inlet 108 and oudet 112 ports are coupled to die bundle of hollow fibers for conducting blood, plasma, or water into and out of die hemoconcentrator. One or more ports 116 and 120 can also be present in the wall of die housing for conducting blood, plasma, or water into or out of the chamber. A vacuum line 124 is also preferably coupled to d e hemoconcentrator for removing water therefrom. The vacuum line in FIG. 2 is coupled to a port 120 in the wall of the housing. A collection vessel 128 and vacuum pump 132 are also coupled to d e vacuum line. For experimental purposes, pressure ports can be placed at various points in the system for measuring pressure. In FIG. 2, pressure ports 134, 135, 136, 137, and 138 are for measuring, respectively, hemoconcentrator inlet pressure, hemoconcentrator outlet pressure and solute removal device inlet pressure, solute removal device plasma pressure, solute removal device outlet pressure, and hemoconcentrator vacuum pressure. A shunt line 139 from line 52 to line 54 permits the solute removal device 64 to be bypassed. For example, clamping lines 52 and 54 at sites 58 and 60 proximal to the solute removal device permits blood to flow dirough die shunt line directly from the hemoconcentrator to the blood reservoir. In diis configuration, multiple cycles of hemoconcentration can be performed wimout passing through d e solute removal device. Opening such clamps at sites 58 and 60, and clamping the shunt line at site 62 causes d e blood to flow dirough the solute removal device. Thus, the system shown in FIG. 2 permits operation in selected operational modes, such as (1) allowing die blood to flow mrough the solute removal device each time the blood flows rough the hemoconcentrator (simultaneous mode), or (2) allowing the blood to flow through die hemoconcentrator for several cycles and men to flow mrough die solute removal device (sequential mode). A preferred hemoconcentrator for use in me present invention is a BIOFILTER 140 (Research Medical, Inc., Midvale, Utah) containing a porous hollow fiber, cellulose diacetate membrane. Other suitable membrane materials include polyacrylonitrile, polysulfone, polymethylmethacrylate, cellulose acetate, cellulose triacetate, and die like. Preferably, the hemoconcentrator is upstream of the solute removal device 64 so diat blood passing through d e hemoconcentrator is heparinized and has less likelihood of forming clots than if die hemoconcentrator were placed downstream of the solute removal device, particularly where such solute removal device is a heparin removal device. Placing the hemoconcentrator downstream of the heparin removal device increases the likelihood of clots collecting in die hemoconcentrator. Moreover, concentrating the blood also concentrates the targeted solute, e.g. heparin, which makes the solute removal device operate more efficiently. Although die present invention is shown in reference to a CPB circuit, the invention can also be used by connecting die blood salvage circuit to the cardiotomy circuit or by connecting die blood salvage circuit directly to die patient for processing of patient blood. Anodier illustrative embodiment of the present invention is shown in FIG. 4. This system 200 comprises a hemoconcentrator 204 and a pair of selected solute removal devices 208 and 212 coupled to a blood reservoir 216. The blood reservoir could be a cardiotomy reservoir, a CPB circuit, a patient, or the like. The blood reservoir is coupled to device 208 by line 220. A roller pump 224 is disposed on line 220 for pumping the blood dirough die system. One end of line 220 is coupled to me inlet port 228 of device 208, and the odier end of die line 220 is coupled to die blood reservoir. Anodier line 232 is coupled at one end to the outlet port 236 of device 208 and at d e odier end to die inlet port 240 of device 212. Line 244 is coupled at one end to the outlet port 248 of device 212 and at the other end to the blood reservoir. The plasma port 252 of device 208 is coupled by line 256 to die inlet port 260 of me hemoconcentrator 204, and die outlet port 264 of die hemoconcentrator is coupled to the plasma port 268 of device 212 by line 272. The vacuum port 276 of the hemoconcentrator 204 is coupled to a vacuum line 280, which is coupled to a collection vessel 284 and a vacuum pump 288. For experimental purposes, pressure ports 290, 292, 294, 296, 298, and 300 are placed in d e system as shown for taking pressure measurements. The pressure measurements taken at ports 290, 292, 294, 296, 298, and 300 represent, respectively, pressure at the inlet port 228 of device 208, pressure at die oudet port 236 of device 208 and at die inlet port 240 of device 212, pressure at die plasma chamber 304 of device 208 and pressure of inlet port 260 of die hemoconcentrator 204, pressure at the plasma chamber 308 of device 212, pressure at die outlet port 248 of device 212, and vacuum pressure at the vacuum port 276 of the hemoconcentrator 204. A flow probe 312 in line 256 measures the plasma filtration rate of device 208. In this configuration, blood is pumped dirough die first solute removal device 208, and die plasma that is separated from the blood cells is conducted to die hemoconcentrator. In the hemoconcentrator, water and low molecular weight solutes are removed from the plasma and conducted to a collection vessel. The concentrated plasma mat exits die hemoconcentrator is then conducted into the plasma chamber of the second solute removal device, where the plasma is combined widi blood cells again after refiltration. The blood d at exits die second device has mus been subjected to both hemoconcentration and affinity removal of a selected solute. Not all of die plasma separated from e blood in the first solute removal device 208 passes through the hemoconcentrator. A portion of the plasma reenters the hollow fiber membrane by refiltration for remixing with die blood cells, exits die device at outlet port 236, and is transported through line 232 to die second solute removal device 212. In the second solute removal device 212, the plasma can again pass through me pores in me hollow fiber membranes into the plasma chamber 308. In the plasma chamber 308 there can be mixing of plasma with concentrated plasma from the hemoconcentrator and additional affinity removal of selected solutes. The plasma can then return to die hollow fiber membrane by refiltration, where it is mixed widi die blood cells, and eventual returned to die blood reservoir. Preferably, a fine mesh screen is placed at pott 252 of device 208 and at port 268 of device 212 to retain sorbent in me plasma chambers. A variant of e embodiment shown in FIG. 4 is illustrated in FIG. 5, where like reference numbers are used to indicate similar parts. The differences between FIG. 4 and FIG. 5 are in how the plasma and die water removed dierefrom pass through the hemoconcentrator. In FIG. 4, the plasma enters the hemoconcentrator into the chamber that surrounds die hollow fibers, and die water and low molecular weight solutes pass from the chamber through d e pores in the hollow fiber ultrafiltration membrane into the lumens of die hollow fibers and d en into the vacuum line for collection in the collection vessel. In contrast, in the system 316 shown in FIG. 5, the plasma enters the hemoconcentrator into the lumens of the hollow fibers, and me water and low molecular weight solutes pass from the lumens of the hollow fibers through he pores in the hollow fibers into the chamber and then into the vacuum line for collection in me collection vessel. In FIG. 6 there is shown a combination device 142 for carrying out the processes of hemoconcentration and selective removal of a targeted solute. The combination device 142 is placed in a blood salvage circuit 140 coupled to a CPB circuit 144, as in FIG. 1. The blood salvage circuit comprises a pump 148 for pumping blood from the CPB circuit 144 through the combination device 142 and optionally dirough a separate hemoconcentrator 152. The combination device comprises a hollow fiber plasma-separating membrane 156 coupled to an inlet port 160 and an outlet port 164. The hollow fiber plasma-separating membrane 156 is enclosed in a housing 168 diat encompasses a plasma chamber 172 containing a plasma chamber solution 176 and a selective sorbent 180. The hollow fibers have pore sizes in the range of about 0.01 μm to 1.0 μm, as described above. Also contained within the plasma chamber 172 is an ultrafiltration membrane 184 having an outlet port 188. This ultrafiltration membrane is also made of hollow fibers having a molecular weight cut-off in die range of about 10,000 to 100,000, as described above in connection with die hemoconcentrator. Not only can vacuum be applied to enhance hemoconcentration, but die system also accommodates countervalent or dialysis solutions. Blood is pumped into die combination device 142 such diat die blood enters at die inlet arm 160. The blood passes dirough die lumens of the hollow fiber membranes, and die plasma and solutes pass dirough the pores of the membrane into me plasma chamber solution containing a selective sorbent. When selected solutes contact die sorbent, the selected solutes bind to die sorbent, dius depleting die concentration of die selected solute in me plasma. If the outlet port 188 of die ultrafiltration membrane is closed, dien die selected- solute-depleted plasma passes through the pores of die hollow fiber plasma- separating membrane 156 by refiltration and passes out of the device 142 into the blood salvage circuit 140. The solute-depleted blood can optionally be passed dirough a separate hemoconcentrator 152, where water, fluids, and low molecular weight solutes are removed by ultrafiltration, or can pass directly into die CPB circuit 144. In this configuration, die blood can be subjected to simultaneous or sequential hemoconcentration and solute depletion. By opening me outlet port 188 of me ultrafiltration membrane 184, solute-depleted plasma can be subjected to hemoconcentration in the combination device. Preferably, die outlet port 188 is coupled to a vacuum line, similar to what is shown in FIGS. 2, 4, and 5. Water, fluids, and low molecular weight molecules pass mrough me ultrafiltration membrane 184 and are drawn out of die device 142 dirough the outlet port 188 for collection. The pore size of me ultrafiltration membrane 184 can be selected such diat die size of the low molecular weight molecules removed is selectable. Typically, die molecular weight cut-off is in the range of about 10,000 to about 100,000. The concentrated plasma in the plasma chamber reenters the hollow fiber plasma- separating membrane 156 by refiltration, mixes with blood cells in die lumens of me hollow fibers, and passes out of die device dirough the outlet arm 164. As with die blood salvage circuit of FIGS. 2, 4, and 5, d e combination device can be used by connection to die CPB circuit, die cardiotomy circuit, or by connection directly widi die patient for processing of patient blood. The combination device possesses a number of advantages that are not otherwise obtained. For example, the combination device permits blood salvage and targeted solute removal in a single, low cost device. Also, higher pressures can be used for ultrafiltration dian are odierwise possible because the ultrafiltration is done in the plasma phase rather than the whole blood phase. Such higher pressures are not possible in d e whole blood phase because of die resulting lysis of blood cells. Further, the combination device provides for a quick and easy means for responding to die systemic inflammatory response diat accompanies cardiopulmonary bypass in a significant proportion of patients. This systemic inflammatory response is believed to result from the rapid release of certain cytokines into the blood. These cytokines can be removed by using selected sorbents, such as immobilized immunoglobulins, receptors, and/or whole cells, for specific binding of die cytokines. Removal of the cytokines from the blood of a patient undergoing systemic inflammatory response is believed to alleviate such response. Further advantages of die present invention derive from the lack of high transmembrane pressure in the plasma separating and sorbent-containing device. This relatively low transmembrane pressure results in improved rheology as compared to odier devices known in d e art such that die present system can be operated at higher flow throughputs. This higher rate of flow results in less time being needed to process die blood, and consequently less time is needed to treat a patient. Example 1 In this example, pressure and flow data were determined for a plasma separation and sorbent-containing device similar to the plasma sorbent system described in U.S. Patent No. 5,211,850 to Shettigar & McRea and illustrated in FIG. 3. In this example, a plasma sorbent system containing a heparin-specific sorbent (HRD, Research Medical Inc., Midvale, UT) was tested to determine inlet pressure (P m ), oudet pressure (P ^t ), plasma pressure (P p ι asma ), and transmembrane pressure (TMP). Pressure measurements were taken at the inlet line 87, outlet line 89, and plasma port 82. TMP was calculated as die average of inlet and plasma pressures less plasma pressure [(P ιn + P plasrna )/2 - P plasm J. Table 1 shows die results of such an experiment using porcine whole blood as die medium. Blood was pumped dirough me HRD using a SARNS 5000 blood pump. These data show diat die inlet blood pressure (P m ) increases with die increase in blood flow rate through the hollow fiber lumen. The pressure in the plasma chamber (P p _ sma ) also increases proportionately, while the outlet blood pressure (P out ) increases at a much slower rate. The transmembrane pressure (TMP) is a direct measure of me driving force for die filtration rate of fluid from the blood in die inlet arm of the plasma-separating membrane into the plasma chamber. This driving force is seen to be increasing with die increase in the blood flow rate. This test demonstrates that as the P plasnιa increases wim me increase in P, n , two different regions of mass transfer are created. In die inlet arm of the plasma-separating membrane where P ιn > P plasma , there is a positive convection of mass transfer across die membrane through its pores into me plasma chamber solution. However, in the outlet arm of the plasma- separating membrane where P^ < P plasma , this causes a negative or reverse convective mass transfer across die membrane through its pores from the plasma chamber solution into the lumen. Example 2 In this example, a hemoconcentrator (BIOFILTER 140, Research Medical Inc., Midvale, UT) was tested to determine vacuum pressure (P vacuum ), inlet pressure (P In ), outlet pressure (P^,), transmembrane pressure (TMP), and ultrafiltration rate (UFR) at d ree different flow rates using human blood in human clinical trials. TMP was determined as die average of inlet and oudet pressures less vacuum pressure [(P ιn + P o /2 - P vacuum ]. Blood was pumped widi a roller pump from a cardiotomy reservoir or cardiopulmonary bypass circuit into me hemoconcentrator through the inlet port. Water and solutes having a molecular weight lower than that of die molecular weight cut-off of the ultrafiltration membrane passed from the lumens of the hollow fibers through die pores of the membrane into the chamber defined by me housing. A vacuum line was coupled to a port in d e housing and to a collection flask and a vacuum pump for applying reduce pressure to me chamber. Concentrated whole blood passed dirough the outlet port for return to the cardiotomy reservoir or CPB circuit. Tables 2-4 show the results of such experiments at hemoconcentrator flow rates of 200 ml/min, 300 ml/min, and 400 ml/min, respectively. These results show ultrafiltration rates can be manipulated by varying flow rates and vacuum pressures. At a given flow rate, the ultrafiltration rate can generally be increased by increasing die vacuum pressure. Example 3 This example shows an illustrative embodiment of the present invention according to die system shown in FIG. 2, wherein hemoconcentration and heparin removal were carried out simultaneously. The hemoconcentrator was a BIOFILTER 140 and die solute removal device was an HRD for removing heparin. The shunt line was clamped such that blood passed dirough the hemoconcentrator and die solute removal device in each passage dirough die circuit. In this example, bovine whole blood was recirculated through me system at a flow rate of 500 ml/min for 60 minutes. The pressure, ultrafiltration rate, and heparin removal data from this experiment are shown in Table 5. Example 4 This example shows an illustrative embodiment of the present invention according to die system shown in FIG. 2 and according to die procedure of Example 3 except that at die beginning of die experiment the shunt was used to bypass die heparin removal device until a selected volume was removed, and dien me blood was caused to circulate dirough die heparin removal device. Thus, diis example shows that hemoconcentration and heparin removal can be carried out sequentially. It is preferred to perform the hemoconcentration prior to heparin removal, because performing heparin removal prior to hemoconcentration leads to a greater likelihood of clot formation. In this example, bovine whole blood was recirculated dirough die system at a flow rate of 500 ml/min for 60 minutes. The pressure, ultrafiltration rate, and heparin removal data from this experiment are shown in Table 5. Example 5 This example shows an illustrative embodiment of the present invention according to die system shown in FIG. 6, wherein hemoconcentration and selected solute removal were carried out in a single device combining a hemoconcentrator and a solute removal device. Pressure measurements were taken so that inlet pressure (P in ), plasma chamber pressure (P plasma ), outlet pressure (P out ), and vacuum pressure (P vacuum ) were determined. In diis example, bovine whole blood was recirculated dirough the system at a flow rate of 500 ml/min for 60 minutes. The pressure, ultrafiltration rate, and heparin removal data from this experiment are shown in Table 5. Example 6 This example shows an illustrative embodiment of the present invention according to d e system shown in FIG. 4. Pressure measurements were taken at ports 290, 292, 294, 296, 298, and 300, which represent, respectively, pressure at die inlet port of device 208, pressure at die outlet port of device 208 and at die inlet port of device 212, pressure at die plasma chamber of device 208, pressure at me plasma chamber of device 212, pressure at die outlet port of device 212, and vacuum pressure at the vacuum port of the hemoconcentrator. A flow probe 312 in line 256 measured die plasma filtration rate of device 208. In diis example, 3 liters of bovine whole blood at 30°C and a hematocrit of 0.26 was used in the system. The roller pump was a Masterflex Model 7524-00, and the vacuum pump was a GAST Model DOA-P104-AA. The selected solute removal devices were heparin removal devices (HRD, Research Medical Inc.), and die hemoconcentrator was a Biofilter 140 (Research Medical Inc.). Tygon tubing (S-50-HL Class VI, 6.35 mm x 1.59 mm and 4.77 mm x 1.59 mm). The flow probe was a Transonic flow probe No. H6X117 used with a Transonic HT109R flowmeter and 6.35 mm x 1.59 mm tubing. Pressure measurements were taken with a Deltran Disposable Pressure Transducer (Utah Medical, Midvale, Utah). Data collection was with an HP 75000 system. The results of these experiments are shown in Tables 6 and 7. TΛItl.I'.ή 31 TΛIII.R7 Example 7 In this example, the system was configured according to FIG. 5, and the procedure was as in Example 6. The results were similar to those of Example 6.

Claims: CLAIMS We claim: 1. A system for salvaging blood from a patient for the selective removal of a targeted solute in the blood and the removal of water, fluids, and low molecular weight solutes comprising: (a) a hemoconcentrator comprising a porous ultrafiltration membrane having a selected molecular weight cut-off for retaining components selected from the group consisting of cells and solutes with a molecular weight greater than the cut-off and for allowing water, fluids, and solutes with a molecular weight less than the cut-off to be removed from blood or plasma; and (b) a first solute removal device for selectively removing the targeted solute from blood by means of convective and diffusive transport of plasma from said blood across a hollow fiber plasma-separating membrane into a plasma chamber where the selective removal of the targeted solute from non- targeted solutes using a sorbent is accomplished followed by the subsequent transport of the non-targeted solutes across the plasma-separating membrane back into the blood, comprising (i) a closed plasma chamber configured for being filled with a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in said plasma chamber solution under relatively uniform pressure; (ii) the hollow fiber plasma-separating membrane, wherein said plasma-separating membrane has an inlet arm and an outlet arm and is configured for being immersed in said plasma chamber solution in said closed plasma chamber; (iii) at least one sorbent having an affinity for binding said targeted solute, wherein said sorbent is contained in said closed plasma chamber; (iv) means for securing said inlet arm and outlet arm of said plasma-separating membrane in said plasma chamber and closing said chamber to maintain relatively uniform plasma chamber solution pressure; and (v) means for circulating said blood into said inlet arm, through said plasma-separating membrane, and out through said outlet arm; and (c) means for coupling said hemoconcentrator to said first solute removal device to permit liquid communication therebetween and for coupling said hemoncentrator and said first solute removal device to said patient to permit blood to be received from and returned to said patient. 2. The system of claim 1 wherein said the porous ultrafiltration membrane of said hemoconcentrator comprises a plurality of hollow fibers. 3. The system of claim 2 wherein the molecular weight cut-off of said porous ultrafiltration membrane is in the range of about 10,000 to 100,000. 4. The system of claim 3 wherein said porous ultrafiltration membrane is made from a material selected from the group consisting of polyacrylonitrile, polysulfone, polynethylmethacrylate, cellulose acetate, cellulose diacetate, and cellulose triacetate. 5. The system of claim 1 wherein said hollow fiber plasma- separating membrane comprises a bundle of parallel hollow fibers. 6. The system of claim 5 wherein said sorbent is of a size and configuration such that said sorbent is not permeable to the plasma-separating membrane. 7. The system of claim 6 wherein said hollow fibers making up said plasma-separating membrane are constructed of a blood-compatible material having a suitable pore size to allow passage of plasma into the plasma chamber solution while retaining blood cells and platelets from the blood within the hollow fibers. 8. The system of claim 7 wherein the pore sizes in said membrane range between about 0.01 μm to 1.0 μm. 9. The system of claim 8 wherein said hollow fibers of said plasma- separating membrane are made from a material selected from the group consisting of polypropylene, cellulose diacetate, polycarbonate, polyvinylchloride, polyvinylalcohol, polymethylmethacrylate, polyethylene, polysulfone, and polyethylenevinylalcohol. 10. The system according to claim 9 wherein the sorbent comprises a ligand immobilized on a substrate and said ligand is a member selected from the group consisting of enzymes, living tissue, fragments of tissue, cells, antibodies, peptides, macromolecules, nucleic acids, lectins, carbohydrates, and chelating agents. 11. The system of claim 10 wherein said sorbent has affinity for heparin. 12. The system of claim 11 wherein the substrate is agarose. 13. The system of claim 12 wherein the sorbent is poly-L-lysine- coupled agarose. 14. The system of claim 1 wherein said hemoconcentrator and said first solute removal device are configured for simultaneous hemoconcentration and removal of the targeted solute. 15. The system of claim 1 wherein said hemoconcentrator and said first solute removal device are configured for sequential hemoconcentration and removal of the targeted solute. 16. The system of claim 1 wherein said hemoconcentrator has an inlet port and an outlet port and said outlet port of said hemoconcentrator is coupled to the inlet arm of said first solute removal device such that blood passes through said hemoconcentrator for removal of water, fluids, and low molecular weight solutes to result in concentrated blood, which concentrated blood then passes through said first solute removal device for removal of the targeted solute. 17. The system of claim 1 wherein said hemoconcentrator has an inlet port and an outlet port and the outlet arm of said first solute removal device is coupled to the inlet port of said hemoconcentrator such that blood passes through said first solute removal device for removal of the targeted solute resulting in targeted-solute-depleted blood, which targeted-solute- depleted blood then passes through said hemoconcentrator for removal of water, fluids, and low molecular weight solutes. 18. The system of claim 1 wherein said plasma chamber solution is an electrolyte. 19. The system of claim 1 wherein said porous ultrafiltration membrane is contained in said closed plasma chamber such that water, fluids, and low molecular weight solutes can be removed from said plasma by ultrafiltration. 20. The system of claim 1 further comprising a second solute removal device, which comprises (i) a closed plasma chamber configured for being filled with a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in said plasma chamber solution under relatively uniform pressure; (ii) a hollow fiber plasma-separating membrane, wherein said plasma-separating membrane has an inlet arm and an outlet arm and is configured for being immersed in said plasma chamber solution in said closed plasma chamber; (iii) at least one sorbent having an affinity for binding said targeted solute, wherein said sorbent is contained in said closed plasma chamber; (iv) means for securing said inlet arm and outlet arm of said plasma-separating membrane in said plasma chamber and closing said chamber to maintain relatively uniform plasma chamber solution pressure; and (v) means for circulating blood into said inlet arm, mrough said plasma-separating membrane, and out through said outlet arm; wherein the plasma chamber of said first solute removal device is coupled to the inlet port of said hemoconcentrator and the outlet port of said hemoconcentrator is coupled to the plasma chamber of said second solute removal device such that plasma can flow from said first solute removal device through said hemoconcentrator to said second solute removal device such that water, fluids, and low molecular weight solutes can be removed from said plasma by ultrafiltration, and wherein said outlet arm of said first solute removal device is coupled to the inlet arm of said second solute removal device such that blood can flow therebetween. 21. An apparatus for selectively removing a targeted solute from blood by binding said targeted solute to an affinity sorbent and removing water, fluids, and low molecular weight solutes by ultrafiltration, comprising: (a) a closed plasma chamber configured for being filled with a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in said plasma chamber solution under relatively uniform pressure; (b) a hollow fiber plasma-separating membrane having an inlet arm and an outlet arm and configured for being immersed in said plasma chamber solution in said closed plasma chamber; (c) at least one sorbent having an affmity for binding said targeted solute, wherein said sorbent is contained in said closed plasma chamber; (d) means for securing said inlet arm and outlet arm of said plasma- separating membrane in said plasma chamber and closing said chamber to maintain relatively uniform plasma chamber solution pressure; and (e) a porous ultrafiltration membrane disposed in said closed plasma chamber and configured for being immersed in said plasma chamber solution, said ultrafiltration membrane having a selected molecular weight cut-off for allowing water, fluids, and solutes with a molecular weight lower than the cut¬ off to pass therethrough and for retaining solutes with a molecular weight greater than the cut-off and means for withdrawing said water, fluids, and solutes that pass through said ultrafiltration membrane; and (f) means for circulating said blood into said inlet arm such that plasma, including water, fluids, and low molecular weight solutes therein, is transported from said blood across said plasma-separating membrane by convective and diffusive transport into the plasma chamber solution where the selective removal of the targeted solute from non-targeted solutes using said affinity sorbent is accomplished followed by the subsequent transport of the non-targeted solutes across the plasma-separating membrane back into the blood and out through said outlet arm. 22. A system for salvaging blood from a patient for the selective removal of a targeted solute in the blood and the removal of water, fluids, and low molecular weight solutes comprising: (a) a hemoconcentrator comprising an inlet port, an outlet port, and a porous ultrafiltration membrane having a selected molecular weight cut-off for retaining components selected from the group consisting of cells and solutes with a molecular weight greater than the cut-off and for allowing water, fluids, and solutes with a molecular weight less than the cut-off to be removed from blood or plasma; and (b) first and second solute removal devices for selectively removing the targeted solute from blood by means of convective and diffusive transport of plasma from said blood across a hollow fiber plasma-separating membrane into a plasma chamber where the selective removal of the targeted solute from non- targeted solutes using a sorbent is accomplished followed by the subsequent transport of the non-targeted solutes across the plasma-separating membrane back into the blood, each said first and second solute removal device comprising (i) a closed plasma chamber configured for being filled with a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in said plasma chamber solution under relatively uniform pressure; (ii) the hollow fiber plasma-separating membrane, wherein said plasma-separating membrane has an inlet arm and an outlet arm and is configured for being immersed in said plasma chamber solution in said closed plasma chamber; (iii) at least one sorbent having an affinity for binding said targeted solute, wherein said sorbent is contained in said closed plasma chamber; (iv) means for securing said inlet arm and outlet arm of said plasma-separating membrane in said plasma chamber and closing said chamber to maintain relatively uniform plasma chamber solution pressure; and (v) means for circulating said blood into said inlet arm, through said plasma-separating membrane, and out through said outlet arm; (c) means for coupling the plasma chamber of said first solute removal device to the inlet port of said hemoconcentrator and means for coupling the outlet port of said hemoconcentrator to the plasma chamber of said second solute removal device such that plasma can flow from said first solute removal device through said hemoconcentrator to said second solute removal device such that water, fluids, and low molecular weight solutes can be removed from said plasma by ultrafiltration, and means for coupling the outlet arm of said first solute removal device to the inlet arm of said second solute removal device such that blood can flow therebetween; and (d) means for coupling said first and second solute removal devices to said patient to permit blood to be received from and returned to said patient. 23. A method of selectively removing a targeted solute and water, fluids, and low molecular weight solutes from blood comprising: (a) providing a system comprising: (1) a hemoconcentrator comprising a porous ultrafiltration membrane having a selected molecular weight cut-off for retaining components selected from the group consisting of cells and solutes with a molecular weight greater than the cut-off and for allowing water, fluids, and solutes with a molecular weight less than the cut-off to be removed from blood or plasma; and (2) a first solute removal device for selectively removing the targeted solute from blood by means of convective and diffusive transport of plasma from said blood across a hollow fiber plasma- separating membrane into a plasma chamber where the selective removal of the targeted solute from non-targeted solutes using a sorbent is accomplished followed by the subsequent transport of the non-targeted solutes across the plasma-separating membrane back into the blood, comprising (i) a closed plasma chamber configured for being filled with a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in said plasma chamber solution under relatively uniform pressure; (ii) the hollow fiber plasma-separating membrane, wherein said plasma-separating membrane has an inlet arm and an outlet arm and is configured for being immersed in said plasma chamber solution in said closed plasma chamber; (iii) at least one sorbent having an affinity for binding said targeted solute, wherein said sorbent is contained in said closed plasma chamber; (iv) means for securing said inlet arm and outlet arm of said plasma-separating membrane in said plasma chamber and closing said chamber to maintain relatively uniform plasma chamber solution pressure; and (v) means for circulating said blood into said inlet arm, through said plasma-separating membrane, and out through said outlet arm; and (3) means for coupling said hemoconcentrator to said first solute removal device to permit liquid communication therebetween and for coupling said hemoncentrator and said first solute removal device to said patient to permit blood to be received from and returned to said patient; (b) directing said blood from a source into said inlet arm by said means for circulating said blood, through said plasma-separating membrane and out said outlet arm at a volume and a velocity that permits convective and diffusive transport of plasma from said blood across said plasma-separating membrane along the inlet arm of said plasma-separating membrane into said plasma chamber solution; (c) causing said plasma in said plasma chamber solution to come into contact with said sorbent such that said targeted solute is selectively bound to said sorbent; (d) causing said non-targeted solutes to pass by diffusive and convective transport from said plasma chamber solution across the plasma- separating membrane into the blood retained by said plasma-separating membrane and out of said device; (e) causing said blood or plasma to pass through said hemoconcentrator such that water, fluids, and solutes with a molecular weight less than said cut-off pass through said porous ultrafiltration membrane and are withdrawn from said blood or plasma, and said ultrafiltration retains cells and solutes with a molecular weight greater than said cut-off in said blood or plasma. 24. The method of claim 23 wherein said the porous ultrafiltration membrane of said hemoconcentrator comprises a plurality of hollow fibers. 25. The method of claim 24 wherein the molecular weight cut-off of said porous ultrafiltration membrane is in the range of about 10,000 to 100,000. 26. The method of claim 25 wherein said porous ultrafiltration membrane is made from a material selected from the group consisting of polyacrylonitrile, polysulfone, polynethylmethacrylate, cellulose acetate, cellulose diacetate, and cellulose triacetate. 27. The method of claim 23 wherein said hollow fiber plasma- separating membrane comprises a bundle of parallel hollow fibers. 28. The method of claim 27 wherein said sorbent is of a size and configuration such that said sorbent is not permeable to the plasma-separating membrane. 29. The method of claim 28 wherein said hollow fibers making up said plasma-separating membrane are constructed of a blood-compatible material having a suitable pore size to allow passage of plasma into the plasma chamber solution while retaining blood cells and platelets from the blood within the hollow fibers. 30. The method of claim 29 wherein the pore sizes in said membrane range between about 0.01 μm to 1.0 μm. 31. The method of claim 30 wherein said hollow fibers of said plasma-separating membrane are made from a material selected from the group consisting of polypropylene, cellulose diacetate, polycarbonate, polyvinylchloride, polyvinylalcohol, polymethylmethacrylate, polyethylene, polysulfone, and polyethylenevinylalcohol. 32. The method according to claim 31 wherein the sorbent comprises a ligand immobilized on a substrate and said ligand is a member selected from the group consisting of enzymes, living tissue, fragments of tissue, cells, antibodies, peptides, macromolecules, nucleic acids, lectins, carbohydrates, and chelating agents. 33. The method of claim 32 wherein said sorbent has affinity for heparin. 34. The method of claim 33 wherein the substrate is agarose. 35. The method of claim 34 wherein the sorbent is poly-L-lysine- coupled agarose. 36. The method of claim 23 wherein said hemoconcentrator and said first solute removal device are configured for simultaneous hemoconcentration and removal of the targeted solute. 37. The method of claim 23 wherein said hemoconcentrator and said first solute removal device are configured for sequential hemoconcentration and removal of the targeted solute. 38. The method of claim 23 wherein said hemoconcentrator has an inlet port and an outlet port and said outlet port of said hemoconcentrator is coupled to the inlet arm of said first solute removal device such that blood passes through said hemoconcentrator for removal of water, fluids, and low molecular weight solutes to result in concentrated blood, which concentrated blood then passes through said first solute removal device for removal of the targeted solute. 39. The method of claim 23 wherein said hemoconcentrator has an inlet port and an outlet port and the outlet arm of said first solute removal device is coupled to the inlet port of said hemoconcentrator such that blood passes through said first solute removal device for removal of the targeted solute resulting in targeted-solute-depleted blood, which targeted- solute-depleted blood then passes through said hemoconcentrator for removal of water, fluids, and low molecular weight solutes. 40. The method of claim 23 wherein said plasma chamber solution is an electrolyte. 41. The methodo of claim 23 wherein said porous ultrafiltration membrane is contained in said closed plasma chamber such that water, fluids, and low molecular weight solutes can be removed from said plasma by ultrafiltration. 42. The method of claim 23 further comprising a second solute removal device, which comprises (i) a closed plasma chamber configured for being filled with a plasma chamber solution and to freely circulate, equilibrate, and interact plasma in said plasma chamber solution under relatively uniform pressure; (ii) a hollow fiber plasma-separating membrane, wherein said plasma-separating membrane has an inlet arm and an outlet arm and is configured for being immersed in said plasma chamber solution in said closed plasma chamber; (iii) at least one sorbent having an affinity for binding said targeted solute, wherein said sorbent is contained in said closed plasma chamber; (iv) means for securing said inlet arm and outlet arm of said plasma-separating membrane in said plasma chamber and closing said chamber to maintain relatively uniform plasma chamber solution pressure; and (v) means for circulating blood into said inlet arm, through said plasma-separating membrane, and out through said outlet arm; wherein the plasma chamber of said first solute removal device is coupled to the inlet port of said hemoconcentrator and the outlet port of said hemoconcentrator is coupled to the plasma chamber of said second solute removal device such that plasma can flow from said first solute removal device through said hemoconcentrator to said second solute removal device such that water, fluids, and low molecular weight solutes can be removed from said plasma by ultrafiltration, and wherein said outlet arm of said first solute removal device is coupled to the inlet arm of said second solute removal device such that blood can flow therebetween.

Inventors: FOWERS KIRK, MCREA JAMES C, POULSON STEPHANIE, XIA YONG NIAN, FOWERS, KIRK, MCREA, JAMES, C., POULSON, STEPHANIE, XIA, YONG, NIAN
Applicants: RESEARCH MEDICAL INC, RESEARCH MEDICAL, INC.
Application year: 1997
Main classification: B01D36
IPC codes: A61M1, B01D61, B01D63, B01D71