Ultrafiltration membrane, device, bioartificial organ, and related methods

• US 9,403,126 B2
• Filed: 01/10/2008
• Issued: 08/02/2016
• Est. Priority Date: 01/10/2007
• Status: Active Grant

• Current Assignee: Cleveland Clinic Foundation
• Original Assignee: Cleveland Clinic Foundation, Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Fissell, William H., Roy, Shuvo, Fleischman, Aaron, Goldman, Kenneth G.
• Primary Examiner(s): BASS, DIRK R
• Application Number:
  US11/972,502
• Publication Number:
  US 20090131858A1
• Time in Patent Office: 3,127 Days
• Field of Search: 210/243, 210/321.6
• US Class Current: 1/1
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61M 1/1623 Disposition or location of membranes relative to fluids
• CPC Class Codes: A61M 1/267 used for pumping
• CPC Class Codes: B01D 2257/70 Organic compounds not provided for in groups B01D2257/00 - B01D2257/602
• CPC Class Codes: B01D 2313/243 Pumps
• CPC Class Codes: B01D 2321/22 Electrical effects
• CPC Class Codes: B01D 2325/028 Microfluidic pore structures
• CPC Class Codes: B01D 61/145 Ultrafiltration
• CPC Class Codes: B01D 61/18 Apparatus therefor
• CPC Class Codes: B01D 61/20 Accessories; Auxiliary operations
• CPC Class Codes: B01D 67/0034 by micromachining techniques, e.g. using masking and etching steps, photolithography
• CPC Class Codes: B01D 67/0062 by micromachining techniques, e.g. using masking and etching steps, photolithography
• CPC Class Codes: B01D 67/0088 Physical treatment with compounds, e.g. swelling, coating or impregnation
• CPC Class Codes: G01N 1/4077 by other techniques involving separation of suspended solids
• CPC Class Codes: G01N 2001/4088 filtration

Abstract

The present invention relates to ultrafiltration. In particular, the present invention provides nanoporous membranes having pores for generating in vitro and in vivo ultrafiltrate, devices and bioartificial organs utilizing such nanoporous membranes, and related methods (e.g., diagnostic methods, research methods, drug screening). The present invention further provides nanoporous membranes configured to avoid protein fouling with, for example, a polyethylene glycol surface coating.

Claims

1. An ultrafiltration system comprising:

a) a membrane consisting of a plurality of nanofabricated slit shaped pores having a width less than 20 nanometers, wherein said plurality of nanofabricated slit shaped pores are arranged in a rectangular configuration on said membrane, wherein said rectangular configuration is at least a 2;

1 arrangement of said nanofabricated slit shaped pores on said membrane, wherein said nanofabricated slit shaped pores are arranged in the center of said membrane, wherein the distance between said nanofabricated slit shaped pores on said membrane is around 50 nm, wherein the thickness of the membrane is approximately 500 nm, wherein the membrane has a porosity around 20%;

b) a housing containing said membrane; and

c) a fluid delivery passageway with a first end and a second end, said first end positioned outside of said housing, said second end positioned to deliver fluid across said membrane.

2. The system of claim 1, wherein said fluid is delivered across said membrane via perfusion pressure.

3. The system of claim 1, further comprising a pump configured to deliver said fluid across said membrane.

4. The system of claim 1, further comprising an actuator configured to decrease protein fouling of said nanofabricated pores.

5. The system of claim 1, further comprising a control component used to control/monitor extracellular fluid volume.

6. The system of claim 1, wherein the length of said nanofabricated pores is less than 50 μ

m.

7. The system of claim 1, wherein said housing comprises a coating, said coating being biocompatible for in vivo use.

8. The system of claim 1, wherein said system further comprises one or more electrodes positioned on or near said membrane such that an electric field is generated in or near said pores.

9. The system of claim 1, wherein said housing has a length and a width, said length of said housing being less than 300 millimeters and said width of said housing being less than 300 millimeters.

10. The system of claim 1, wherein said membrane has a surface coating selected from the group consisting of polyethylene glycol, oligosaccharide surfactant polymers, heparin, and hyaluronan.

11. The system of claim 1, wherein the material of said membrane is selected from the group consisting of silicon, polysilicon, silicon carbide, ultrananocrystalline diamond, diamond-like-carbond (DLC), silicon dioxide, PMMA, SU-8, PTFE, titanium, silica, silicon nitride, polytetrafluorethylene, polymethylmethacrylate, polystyrene, and silicone.

12. An ultrafiltration system comprising:

a) a membrane consisting of a plurality of nanofabricated slit shaped pores having a width less than 20 nanometers, wherein said plurality of nanofabricated slit shaped pores are arranged in a rectangular configuration on said membrane, wherein said rectangular configuration is at least a 2;

1 arrangement of said nanofabricated slit shaped pores on said membrane, wherein said nanofabricated slit shaped pores are arranged in the center of said membrane, wherein the distance between said nanofabricated slit shaped pores on said membrane is around 50 nm, wherein the thickness of the membrane is approximately 500 nm, wherein the membrane has a porosity around 20%, wherein said membrane has a surface coating selected from the group consisting of polyethylene glycol, oligosaccharide surfactant polymers, heparin, and hyaluronan;

b) a housing containing said membrane; and

c) a fluid delivery passageway with a first end and a second end, said first end positioned outside of said housing, said second end positioned to deliver fluid across said membrane.

13. The system of claim 12, wherein said fluid is delivered across said membrane via perfusion pressure.

14. The system of claim 12, further comprising a pump configured to deliver said fluid across said membrane.

15. The system of claim 12, further comprising an actuator configured to decrease protein fouling of said nanofabricated pores.

16. The system of claim 12, further comprising a control component used to control/monitor extracellular fluid volume.

17. The system of claim 12, said plurality of nanofabricated pores having a width less than 20 nanometers.

18. The system of claim 12, wherein the length of said nanofabricated pores is less than 50 μ

m.

19. The system of claim 12, wherein said housing comprises a coating, said coating being biocompatible for in vivo use.

20. The system of claim 12, wherein said system further comprises one or more electrodes positioned on or near said membrane such that an electric field is generated in or near said pores.

21. The system of claim 12, wherein said housing has a length and a width, said length of said housing being less than 300 millimeters and said width of said housing being less than 300 millimeters.

22. The system of claim 12, wherein the material of said membrane is selected from the group consisting of silicon, polysilicon, silicon carbide, ultrananocrystalline diamond, diamond-like-carbond (DLC), silicon dioxide, PMMA, SU-8, PTFE, titanium, silica, silicon nitride, polytetrafluorethylene, polymethylmethacrylate, polystyrene, and silicone.

23. An ultrafiltration system comprising:

a) a membrane consisting of a plurality of nanofabricated slit shaped pores having a width less than 20 nanometers, wherein said plurality of nanofabricated slit shaped pores are arranged in a rectangular configuration on said membrane, wherein said rectangular configuration is at least a 2;

1 arrangement of said nanofabricated slit shaped pores on said membrane, wherein the distance between said nanofabricated slit shaped pores on said membrane is around 50 nm, wherein the thickness of the membrane is approximately 500 nm, wherein the membrane has a porosity around 20%, wherein said nanofabricated slit shaped pores are arranged in the center of said membrane;

said membrane having a surface coating selected from the group consisting of polyethylene glycol, oligosaccharide surfactant polymers, heparin, and hyaluronan;

b) a housing containing said membrane and said electrode; and

c) a fluid delivery passageway with a first end and a second end, said first end positioned outside of said housing, said second end positioned to deliver fluid across said membrane.

24. The system of claim 23, wherein said fluid is delivered across said membrane via perfusion pressure.

25. The system of claim 23, further comprising a pump configured to deliver said fluid across said membrane.

26. The system of claim 23, further comprising an actuator configured to decrease protein fouling of said nanofabricated pores.

27. The system of claim 23, wherein the material of said membrane is selected from the group consisting of silicon, polysilicon, silicon carbide, ultrananocrystalline diamond, diamond-like-carbond (DLC), silicon dioxide, PMMA, SU-8, PTFE, titanium, silica, silicon nitride, polytetrafluorethylene, polymethylmethacrylate, polystyrene, and silicone.

28. The system of claim 23, further comprising a control component used to control/monitor extracellular fluid volume.

29. The system of claim 23, wherein the length of said nanofabricated pores is less than 50 μ

m.

30. The system of claim 23, wherein said housing comprises a coating, said coating being biocompatible for in vivo use.

31. The system of claim 23, wherein said system further comprises one or more electrodes positioned on or near said membrane such that an electric field is generated in or near said pores.

32. The system of claim 23, wherein said housing has a length and a width, said length of said housing being less than 300 millimeters and said width of said housing being less than 300 millimeters.

33. An implantable ultrafiltration device comprising:

a) a membrane consisting of a plurality of nanofabricated slit shaped pores having a width less than 20 nanometers, wherein said plurality of nanofabricated slit shaped pores are arranged in a rectangular configuration on said membrane, wherein said rectangular configuration is at least a 2;

1 arrangement of said nanofabricated slit shaped pores on said membrane, wherein said nanofabricated slit shaped pores are arranged in the center of said membrane, wherein the distance between said nanofabricated slit shaped pores on said membrane is around 50 nm, wherein the thickness of the membrane is approximately 500 nm, wherein the membrane has a porosity around 20%;

said membrane having a surface coating selected from the group consisting of polyethylene glycol, oligosaccharide surfactant polymers, heparin, and hyaluronan;

b) a biocompatible housing containing said membrane; and

c) a fluid delivery passageway with a first end and a second end, said first end positioned outside of said housing, said second end positioned to delivery fluid across said membrane.

34. The device of claim 33, wherein said fluid is delivered across said membrane via perfusion pressure.

35. The device of claim 33, further comprising a pump configured to deliver said fluid across said membrane.

36. The device of claim 33, further comprising an actuator configured to decrease protein fouling of said nanofabricated pores.

37. The device of claim 33, further comprising a control component used to control/monitor extracellular fluid volume.

38. The device of claim 33, wherein the material of said membrane is selected from the group consisting of silicon, polysilicon, silicon carbide, ultrananocrystalline diamond, diamond-like-carbond (DLC), silicon dioxide, PMMA, SU-8, PTFE, titanium, silica, silicon nitride, polytetrafluorethylene, polymethylmethacrylate, polystyrene, and silicone.

39. The device of claim 33, wherein the length of said nanofabricated pores is less than 50 μ

m.

40. The device of claim 33, wherein said housing comprises a coating, said coating being biocompatible for in vivo use.

41. The device of claim 33, further comprising a population of cells attached to said membrane.

42. The device of claim 41, wherein said cells are selected from the group consisting of renal tubule cells, pancreatic cells, hepatic cells, thyroid cells, adrenal cells, parathyroid cells, pituitary cells, hypothalamic cells, gonadal cells, prokaryotic cells, duodenal cells, gastric cells, intestinal cells, muscle cells, fibroblast cells, and endothelial cells.

43. The device of claim 33, wherein said housing has physical dimensions that permit said device to be used in a human subject, in vivo.

44. The device of claim 33, further comprising one or more sensors associated with said membrane, wherein said sensor is configured to monitor filtration parameters.

45. The device of claim 44, wherein said one or more sensors are selected from the group consisting of a pressure sensor configured to monitor transmembrane pressure, a proteins sensor configured to monitor protein leakage/membrane breakdown, an optical blood sensor configured to monitor membrane rupture, and urea sensor configured to monitor urea clearance.