Salvage of autologous blood via selective membrane/sorption technologies

• US 5,858,238 A
• Filed: 03/07/1997
• Issued: 01/12/1999
• Est. Priority Date: 03/08/1996
• Status: Expired due to Fees

• Current Assignee: Jostra Bentley, Inc.
• Original Assignee: Baxter Research Medical, Inc.
• Inventors: McRea, James C., Xia, Yong Nian, Fowers, Kirk, Poulsen, Stephanie
• Primary Examiner(s): KIM, SUN U
• Application Number:
  US08/813,504
• Time in Patent Office: 676 Days
• Field of Search: 210/644, 210/645, 210/650, 210/651, 210/653, 210/654, 210/655, 210/805, 210/806, 210/252, 210/253, 210/257.2, 210/255, 210/263, 210/321.6, 210/321.72 , 210/323.1, 210/433.1, 210/500.23, 210/500.21, 210/321.78, 210/321.79, 210/321.8, 210/321.87, 210/321.88, 210/321.89, 435/174, 435/177, 435/178, 436/177, 436/178, 530/412, 530/414, 530/413, 530/810, 530/812, 530/813, 530/814, 604/4, 604/5, 604/6
• US Class Current: 210/645
• CPC Class Codes: A61M 1/3427 back through the membrane, e.g. by inverted trans-membrane pressure [TMP]
• CPC Class Codes: A61M 1/3472 with treatment of the filtrate
• CPC Class Codes: A61M 1/3475 with filtrate treatment agent in the same enclosure as the membrane
• CPC Class Codes: A61M 1/3482 by filtrating the filtrate using another cross-flow filter, e.g. a membrane filter
• CPC Class Codes: A61M 1/3493 using treatment agents in suspension
• CPC Class Codes: A61M 1/3603 in the same direction
• CPC Class Codes: A61M 1/3621 Extra-corporeal blood circuits single-needle circuits A61M1/30
• CPC Class Codes: A61M 1/3675 Deactivation
• CPC Class Codes: B01D 2313/40 Adsorbents within the flow path
• CPC Class Codes: B01D 2315/06 Submerged-type; Immersion type
• CPC Class Codes: B01D 61/00 Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor separation of gases or vapours by diffusion B01D53/22
• CPC Class Codes: B01D 61/145 Ultrafiltration
• CPC Class Codes: B01D 61/146 comprising multiple ultrafiltration steps
• CPC Class Codes: B01D 61/243 Dialysis
• CPC Class Codes: B01D 63/046 in separate housings

Abstract

Methods and apparatuses for salvaging blood from a patient are disclosed. A blood salvaging and/or blood processing circuit coupled to a cardiopulmonary bypass circuit, cardiotomy circuit, or directly to the patient comprises a hemocentrator for removing water, fluids, and low molecular weight solutes by ultrafiltration and a sorbent-containing plasma separator for removing a selected solute, such as heparin. A combination device for salvaging blood comprises a closed plasma chamber containing a plasma chamber solution, a hollow fiber plasma-separating membrane for receiving blood and permitting plasma to be transported therethrough into the plasma chamber solution and for refiltering the treated plasma back into the blood circuit, a selective sorbent for contacting the selected solute in the plasma and binding the selected solute, and an ultrafiltration membrane for removing water, fluids, and low molecular weight components from the plasma.

Claims

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 an inlet port, and 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) 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 closed 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 hollow fiber plasma-separating membrane back into the blood, comprising

(i) the 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 hollow fiber 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 hollow fiber plasma-separating membrane in said closed plasma chamber; and

(v) means for circulating said blood into said inlet arm, through said hollow fiber 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 hemoconcentrator 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 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 hollow fiber plasma-separating membrane.

7. The system of claim 6 wherein said hollow fibers making up said hollow fiber 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 hollow fibers of said hollow fiber plasma-separating membrane range between about 0.01 μ

m to 1.0 μ

m.

9. The system of claim 8 wherein said hollow fibers of said hollow fiber 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 is disposed within said closed plasma chamber of said first solute removal device in fluid communication with said plasma chamber solution to thereby effect simultaneous hemoconcentration and removal of the targeted solute.

15. The system of claim 1 wherein said hemoconcentrator is disposed in fluid communication with said first solute removal device such that said blood is permitted to pass from said hemoconcentrator to said first solute removal device, or vice-versa, to thereby effect sequential hemoconcentration and removal of the targeted solute or sequential removal of the targeted solute and hemoconcentration, respectively.

16. The system of claim 1 wherein 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 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 hollow fiber 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 hollow fiber plasma-separating membrane in said closed plasma chamber; and

(v) means for circulating blood into said inlet arm, through said hollow fiber plasma-separating membrane, and out through said outlet arm;

wherein the closed 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 closed 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 affinity 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 hollow fiber plasma-separating membrane in said close plasma chamber; 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 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 hollow fiber 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 hollow fiber 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 closed 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 hollow fiber plasma-separating membrane back into the blood, each said first and second solute removal device comprising

(i) the 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 hollow fiber plasma-separating membrane has an inlet aim 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 hollow fiber plasma-separating membrane in said closed plasma chamber; and

(v) means for circulating said blood into said inlet arm, through said hollow fiber plasma-separating membrane, and out through said outlet arm;

(c) means for coupling the closed 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 closed 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 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

(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 closed 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 hollow fiber plasma-separating membrane back into the blood, comprising

(i) the 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 hollow fiber 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 hollow fiber plasma-separating membrane in said closed plasma chamber; and

(v) means for circulating said blood into said inlet arm, through said hollow fiber 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 hemoconcentrator and said first solute removal device to a blood source to permit blood to be received from and returned to said blood source;

(b) directing said blood from said blood source into said inlet arm by said means for circulating said blood, through said hollow fiber plasma-separating membrane and out said outlet arm at a volume and a velocity that permits convective and convective and diffusive transport of plasma from said blood across said hollow fiber plasma-separating membrane along the inlet arm of said hollow fiber 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 hollow fiber plasma-separating membrane into the blood retained by said hollow fiber plasma-separating membrane and out of said first solute removal 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 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 hollow fiber plasma-separating membrane.

29. The method of claim 28 wherein said hollow fibers making up said hollow fiber 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 hollow fibers of said hollow fiber plasma-separating membrane range between about 0.01 μ

m to 1.0 μ

m.

31. The method of claim 30 wherein said hollow fibers of said hollow fiber 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 is disposed within said closed plasma chamber of said first solute removal device in fluid communication with said plasma chamber solution to thereby effect simultaneous hemoconcentration and removal of the targeted solute.

37. The method of claim 23 wherein said hemoconcentrator is disposed in fluid communication with said first solute removal device such that said blood is permitted to pass from said hemoconcentrator to said first solute removal device, or vice versa, to thereby effect sequential hemoconcentration and removal of the targeted solute or sequential removal of the targeted solute and hemoconcentration, respectively.

38. The method of claim 23 wherein 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 outlet arm of said first solute removal device is coupled to the inlet port of said hemoconcentrator such that blood passed 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 method 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 comprises 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, herein said hollow fiber 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 hollow fiber plasma-separating membrane in said closed plasma chamber; and

(v) means for circulating blood into said inlet arm, through said hollow fiber plasma-separating membrane, and out through said outlet arm;

wherein the closed 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 closed 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.