Ultrafiltration membrane device, bioartificial organ, and related methods

• US 9,802,158 B2
• Filed: 07/29/2016
• Issued: 10/31/2017
• 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:
  US15/223,941
• Publication Number:
  US 20160332119A1
• Time in Patent Office: 459 Days
• Field of Search: 210243, 2103216
• 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 housing comprising a first chamber and a second chamber, wherein the first chamber and the second chamber are separated by a membrane consisting essentially of a plurality of nanofabricated pores having a width less than 20 nanometers, wherein the distance between nanofabricated 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 first inlet positioned to deliver fluid into the first chamber; and

c) a first outlet positioned to remove fluid out of the first chamber.

2. 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.

3. The system of claim 1, wherein the nanofabricated pores are modified with polyethyleneglycol.

4. 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.

5. The system of claim 1, wherein said nanofabricated pores separate the first chamber from the second chamber.

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

7. The system of claim 1, wherein said plurality of nanofabricated pores have a slit shape.

8. The system of claim 1, wherein said nanofabricated pores are arranged in the center of said membrane.

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

10. 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.

11. The system of claim 1, wherein the first inlet and first outlet are positioned in the housing.

12. The system of claim 1, wherein the inlet and outlet further comprise a conduit.

13. The system of claim 12, wherein the conduit comprises a tubing.

14. The system of claim 13, wherein the tubing is attached to the inlet and outlet by a clamp or threaded connection.

15. The system of claim 1, wherein the inlet and outlet pass through the housing.

16. The system of claim 1, wherein the inlet and outlet comprise a spheroid, elliptical, or slit shape.

17. The system of claim 1, wherein the first chamber comprises a biological fluid.

18. The system of claim 17, wherein the biological fluid is blood.

19. The system of claim 18, wherein the blood enters the first chamber through the inlet.

20. The system of claim 18, wherein blood exits the first chamber through the outlet.

21. The system of claim 1, wherein the second chamber comprises a dialysate.

22. The system of claim 1, wherein the first chamber is in fluid connection with the second chamber.

23. The system of claim 19, wherein a filtrate in the blood passes through the nanofabricated pores of the membrane.

24. The system of claim 23, wherein the second chamber is positioned to receive the filtrate.