Ultrafiltration membrane,device, bioartificial organ, and methods

• US 20060213836A1
• Filed: 05/19/2006
• Published: 09/28/2006
• Est. Priority Date: 09/11/2002
• Status: Active Grant

• Current Assignee: Cleveland Clinic Foundation
• Original Assignee: Cleveland Clinic Foundation
• Inventors: Humes, H. David, Roy, Shuvo, Fleischman, Aaron, Fissell, William H. IV
• Granted Patent: US 7,540,963 B2
• Time in Patent Office: Days
• US Class Current: 210/645
• CPC Class Codes: A61M 1/1678 intracorporal peritoneal dialysis A61M1/28
• CPC Class Codes: A61M 1/34 Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
• CPC Class Codes: A61M 1/3403 Regulation parameters
• CPC Class Codes: A61M 1/3406 Physical characteristics of the filtrate, e.g. urea
• CPC Class Codes: A61M 1/3489 by biological cells, e.g. bioreactor
• CPC Class Codes: A61M 2205/3331 Pressure; Flow
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: B01D 2323/38 Graft polymerization
• CPC Class Codes: B01D 2325/028 Microfluidic pore structures
• CPC Class Codes: B01D 2325/28 Degradation or stability over time
• CPC Class Codes: B01D 57/02 by electrophoresis treatment of water, waste water, sewage or sludge by electrophoresis C02F1/469; electrophoretic production of compounds or non-metals C25B7/00; investigating or analysing materials by using electrophoresis G01N27/26
• CPC Class Codes: B01D 61/18 Apparatus therefor
• CPC Class Codes: B01D 61/28 Apparatus therefor
• CPC Class Codes: B01D 61/425 Electro-ultrafiltration
• CPC Class Codes: B01D 67/0058 by selective elimination of components, e.g. by leaching
• CPC Class Codes: B01D 67/0072 by deposition from the gaseous phase, e.g. sputtering, CVD, PVD
• CPC Class Codes: B01D 67/0086 Mechanical after-treatment
• CPC Class Codes: B01D 67/0088 Physical treatment with compounds, e.g. swelling, coating or impregnation
• CPC Class Codes: B01D 67/0093 Chemical modification
• CPC Class Codes: B01D 71/027 Silicium oxide
• CPC Class Codes: C12N 13/00 : Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: G01N 2001/4016 : being a selective membrane, e.g. dialysis or osmosis
• CPC Class Codes: G01N 27/3271 : Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001

Abstract

The present invention relates to ultrafiltration. In particular, the present invention provides a compact ultrafiltration device and methods for generating an ultrafiltrate, both of which can be used for a variety of applications, including, but not limited to filtering blood, diagnostic applications, and as a bioreactor.

Claims

1. An ultrafiltration system comprising:

a) a membrane comprising micromachined pores having a length and a width, said length being less than 200 microns and said width being less than 200 nanometers, wherein the ratio of said length to said width is at least 5;

1;

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 delivery fluid across said membrane.

2. The system of claim 1, wherein said length is less than 100 microns.

3. The system of claim 1, wherein said width is less than 100 nanometer.

4. The system of claim 1, wherein said ratio is at least 10:

1.

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

6. 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.

7. 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 millmeters.

8-44. -44. (canceled)

45. A method of filtering a biological fluid comprising:

a) providing an ultrafiltration system comprising

i) a membrane comprising micromachined pores having a length and a width, said length being less than 200 microns and said width being less than 200 nanometers, wherein the ratio of said length to said width is at least 5;

1;

ii) a housing containing said membrane; and

iii) 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;

b) connecting said system to a subject'"'"'s vasculture; and

c) passing biological fluid from said vasculature through said system to generate filtered biological fluid.

46. The method of claim 45, wherein said connecting comprises placing said system into a subject.

47. The method of claim 45, wherein said filtered fluid is substantially free of proteins.

48. The method of claim 45, wherein an electric field is produced under conditions such that said pores provide a charge and size selective barrier to proteins.

49. The method of claim 48, wherein said electric field is produced under conditions such that protein fouling is reduced in said pores.

50. The method of claim 45, wherein said filtered fluid comprises hemofiltered fluid.

51. A method of filtering a biological fluid comprising:

a) providing a bioartificial ultrafiltration device comprising;

i) a housing;

ii) an inlet port passing through said housing, said inlet port configured to receive a biological fluid;

iii) an outlet port passing through said housing, said outlet port configured to return a biological fluid to a subject;

iv) a membrane contained in said housing, said membrane comprising micromachined pores; and

v) a population of cells attached to said membrane;

b) connecting said system to a subject'"'"'s vasculture; and

c) passing biological fluid from said vasculature through said device to generate filtered biological fluid.

52. The method of claim 51, wherein said connecting comprises placing said system into a subject.

53. The method of claim 51, wherein said filtered fluid is substantially free of proteins.

54. The method of claim 51, wherein an electric field is produced under conditions such that said pores provide a charge and size selective barrier to proteins.

55. The method of claim 54, wherein said electric field is produced under conditions such that protein fouling is reduced in said pores.

56. The method of claim 51, wherein said filtered fluid comprises hemofiltered fluid.

57. The method of claim 51, wherein said pores have a length and a width, said length being less than 200 microns and said width being less than 200 nanometers, wherein the ratio of said length to said width is at least 5:

1.

58. The method of claim 51, wherein said device further comprises one or more electrodes positioned on or near said membrane such that an electric field is generated in or near said pores.

59. The method of claim 51, 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.