ULTRATHIN PARYLENE-C SEMIPERMEABLE MEMBRANES FOR BIOMEDICAL APPLICATIONS

• US 20130143326A1
• Filed: 01/20/2012
• Published: 06/06/2013
• Est. Priority Date: 12/05/2011
• Status: Active Grant

• Current Assignee: California Institute of Technology, University of Southern California
• Original Assignee: California Institute of Technology, University of Southern California
• Inventors: Tai, Yu-Chong, Lu, Bo, Humayun, Mark
• Granted Patent: US 8,877,489 B2
• Time in Patent Office: Days
• US Class Current: 435/401
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: B01D 2325/06 Surface irregularities
• CPC Class Codes: B01D 71/44 Polymers obtained by reactions only involving carbon-to-carbon unsaturated bonds, not provided for in a single one of groups B01D71/26-B01D71/42
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2535/10 Patterned coating
• CPC Class Codes: C12N 2539/00 Supports and/or coatings for cell culture characterised by properties
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

Thin parylene C membranes having smooth front sides and ultrathin regions (e.g., 0.01 μm to 5 μm thick) interspersed with thicker regions are disclosed. The back sides of the membranes can be rough compared with the smooth front sides. The membranes can be used in vitro to grow monolayers of cells in a laboratory or in vivo as surgically implantable growth layers, such as to replace the Bruch'"'"'s membrane in the eye. The thin regions of parylene are semipermeable to allow for proteins in serum to pass through, and the thick regions give mechanical support for handling by a surgeon. The smooth front side allows for monolayer cell growth, and the rough back side helps prevents cells from attaching there.

Claims

1. A synthetic semipermeable membrane apparatus, comprising:

a membrane having a smooth front side, a back side, and spatially interspersed thin and thick regions between the smooth front side and the back side, the thin regions being a predetermined thickness of parylene, the predetermined thickness selected from a thickness between 0.01 μ

m to 5 μ

m, the thick regions comprising parylene or another material and being at least 2 times thicker than the predetermined thickness of the thin regions, the interspersion of the thin and thick regions occurring in a random or patterned array with an average feature size of about 1 μ

m to 30 μ

m.

2. The apparatus of claim 1 wherein the thin regions of parylene comprise parylene C.

3. The apparatus of claim 2 wherein the thin regions of parylene C are between 0.15 μ

m to 0.8 μ

m thick,

thereby having a molecular weight exclusion limit larger than 70 kDa and allowing passage of proteins in serum.

4. The apparatus of claim 1 wherein the interspersion of the thin and thick regions occurring in the random or patterned array were produced by lithographic etching of the back side of the membrane.

6. The apparatus of claim 1 wherein the predetermined thickness of the thin regions is selected based on suitability for growing cells selected from the group consisting of cartilage trabeculae, heart muscle, and retinal pigment epithelium (RPE) cells.

7. The apparatus of claim 1 wherein the predetermined thickness is selected from a thickness between 0.1 μ

m to 10 μ

m.

8. The apparatus of claim 7 wherein the predetermined thickness is about 1 μ

m and the thick regions are about 3 μ

m to 6 μ

m thick,

thereby allowing diffusion of cell nutrients and cell waste through the membrane to cells, facilitating cell growth as a monolayer on the membrane.

10. The apparatus of claim 1 further comprising:

a frame substantially surrounding the membrane, the frame being at least 2 times thicker than the predetermined thickness of the thin regions.

11. The apparatus of claim 1 wherein thick regions near a perimeter of the membrane have relatively sharp features and thick regions toward a center of the membrane have relatively smooth features.

14. The apparatus of claim 1 wherein the thick regions are substantially contiguous with one another and the thin regions comprise recesses in the membrane.

15. The apparatus of claim 14 wherein the thin regions comprise non-through holes in the back side of the membrane.

16. The apparatus of claim 1 wherein the interspersion array is a regular array having a constant feature size.

5. (canceled)

9. (canceled)

12-13. -13. (canceled)

17. A synthetic semipermeable membrane apparatus, comprising:

a supporting film having a plurality of through perforations extending from a first side to an opposing, second side of the supporting film; and

a 0.01- to 5-μ

m thin parylene layer covering an opening of each perforation of the supporting film.

20. The apparatus of claim 17 wherein the covered openings of the perforations are even with a surface of the first side of the supporting film, thereby forming a substantially smooth surface on the first side.

21. The apparatus of claim 20 further comprising:

a porous backfill within each perforation, the backfill having a surface even with a surface of the second side of the supporting film, thereby forming a substantially smooth surface on the second side.

23. The apparatus of claim 17 wherein the covered openings of the perforations are on the first side of the supporting film and the thin parylene layer coating extends over walls of the perforations and over a surface of the opposing, second side of the supporting film.

27. The apparatus of claim 17 wherein the perforations in the supporting film were formed by etching and the thin parylene layer was coated using chemical vapor deposition (CVD).

18-19. -19. (canceled)

22. (canceled)

24-26. -26. (canceled)

28-29. -29. (canceled)

30. A process for fabricating a synthetic semipermeable membrane, the process comprising:

providing a supporting film having through perforations extending from a first side to an opposing, second side of the supporting film;

laying the first side of the supporting film against a smooth substrate surface;

depositing a 0.01- to 5-μ

m thin parylene layer over the supporting film sufficient to cover a bottom of each perforation of the supporting film to form a membrane with a smooth first side; and

removing the membrane from the smooth substrate surface.

31. The process of claim 30 wherein the thin parylene layer comprises parylene C.

32. The process of claim 31 wherein the thin parylene C layer is deposited to between 0.15 μ

m to 0.8 μ

m thick,

thereby having a molecular weight exclusion limit larger than 70 kDa and allowing passage of proteins in serum.

33-43. -43. (canceled)