Microfabricated filter with specially constructed channel walls, and containment well and capsule constructed with such filters

• US 6,044,981 A
• Filed: 08/25/1998
• Issued: 04/04/2000
• Est. Priority Date: 03/07/1994
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Ferrari, Mauro, Chu, Wen-Hwa
• Primary Examiner(s): Drodge, Joseph W.
• Application Number:
  US09/139,883
• Time in Patent Office: 588 Days
• Field of Search: 210/321.83, 210/321.84, 210/483, 210/484, 210/490, 210/500.22, 210/500.25, 210/500.26, 216/2, 216/56, 424/422-424, 424/451, 604/890.1, 604/891.1, 604/892.1, 623/11, 623/12, 422/100, 422/101
• US Class Current: 210/490
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: B01D 2323/08 Specific temperatures applied
• CPC Class Codes: B01D 2323/10 Specific pressure applied
• CPC Class Codes: B01D 2325/02 Details relating to pores or porosity of the membranes
• CPC Class Codes: B01D 2325/0283 Pore size
• CPC Class Codes: B01D 2325/04 Characteristic thickness
• CPC Class Codes: B01D 39/1692 Other shaped material, e.g. perforated or porous sheets
• CPC Class Codes: B01D 39/20 of inorganic material, e.g. asbestos paper, metallic filtering material of non-woven wires porous ceramic material C04B38/00 ; sintering metals C22C1/04; making porous sintered metal bodies B22F3/10, honeycomb filters B01D46/2418, materials used for filtering exhaust gases of an internal combustion engine F01N3/022, ceramic honeycomb structures C04B38/0006
• CPC Class Codes: B01D 67/0058 by selective elimination of components, e.g. by leaching
• CPC Class Codes: B01D 67/0062 by micromachining techniques, e.g. using masking and etching steps, photolithography
• CPC Class Codes: B01D 67/0072 by deposition from the gaseous phase, e.g. sputtering, CVD, PVD
• CPC Class Codes: B01D 67/0083 Thermal after-treatment
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01D 69/12 Composite membranes; Ultra-thin membranes
• CPC Class Codes: B01D 71/02 Inorganic material
• CPC Class Codes: B01D 71/0213 Silicon
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: B81B 2201/10 Microfilters, e.g. for gas or fluids
• CPC Class Codes: B81B 3/007 For controlling stiffness, e.g. ribs
• CPC Class Codes: B81C 1/00087 : Holes
• CPC Class Codes: B81C 1/00246 : Monolithic integration, i.e. micromechanical structure and electronic processing unit are integrated on the same substrate
• CPC Class Codes: B81C 2201/014 : by depositing an etch stop layer, e.g. silicon nitride, silicon oxide, metal
• CPC Class Codes: B81C 2201/032 : LIGA process
• CPC Class Codes: B81C 2203/0728 : Pre-CMOS, i.e. forming the micromechanical structure before the CMOS circuit
• CPC Class Codes: B81C 2203/075 : the electronic processing unit being integrated into an element of the micromechanical structure
• CPC Class Codes: C04B 41/4582 : Porous coatings, e.g. coating containing porous fillers
• CPC Class Codes: C23C 16/01 : on temporary substrates, e.g. substrates subsequently removed by etching
• CPC Class Codes: G03F 7/00 : Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor using photoresist structures for special production processes, see the relevant places, e.g. B44C, H01L, e.g. H01L21/00, H05K
• CPC Class Codes: G03F 7/0015 : Production of aperture devices, microporous systems or stamps

Abstract

Microfabricated filters utilizing a bulk substrate structure and a thin film structure and a method for constructing such filters. The pores of the filters are defined by spaces between the bulk substrate structure and the thin film structure and are of substantially uniform width, length and distribution. The width of the pores is defined by the thickness of a sacrificial layer and therefore may be smaller than the limit of resolution obtainable with photolithography. The filters provide enhanced mechanical strength, chemical inertness, biological compatibility, and throughput. The filters are constructed using relatively simple fabrication techniques. Also, microfabricated containment wells and capsules constructed with such filters for the immunological isolation of cell transplants and a method for constructing such containment wells and capsules. The pores of the wells and capsules are large enough to let a desired biologically-active molecular product through, while blocking the passage of all larger immunological molecules. The containment wells and capsules provide enhanced biological compatibility and useful life.

Claims

1. A method for forming a microfabricated filter, comprising the steps of:

providing a bulk substrate having a first surface;

forming openings in said first surface of said bulk substrate;

forming a sacrificial layer over at least part of said first surface of said bulk substrate;

forming a thin film layer over at least part of said first surface of said bulk substrate and said sacrificial layer;

forming openings through said thin film layer, wherein said openings through said thin film layer expose a portion of said sacrificial layer and are positioned relative to said openings in said bulk substrate such that said openings in said bulk substrate are at least partially blocked by said thin film structure and said openings in said thin film structure are at least partially blocked by said bulk substrate;

etching a second surface of said bulk substrate opposite said first surface of said bulk substrate through to said openings in said first surface of said bulk substrate, wherein said etching forms openings through said bulk substrate; and

removing said sacrificial layer.

2. The method of claim 1, wherein said method utilizes only a single photolithographic mask.

3. A method for forming a microfabricated filter, comprising the steps of:

providing a bulk substrate;

forming an etch-stop layer within a first surface of said bulk substrate;

forming openings in said etch-stop layer using a first predetermined etching process, said openings extending through said etch-stop layer into said bulk substrate;

forming a sacrificial layer over at least part of said etch-stop layer;

forming a thin film layer over at least part of said etch-stop layer and said sacrificial layer;

forming openings through said thin film layer using said first predetermined etching process, wherein said openings through said thin film layer expose a portion of said sacrificial layer and are positioned relative to said openings in said bulk substrate such that said openings in said bulk substrate are at least partially blocked by said thin film structure and said openings through said thin film structure are at least partially blocked by said bulk substrate, and wherein said first predetermined etching process does not etch said bulk substrate, said etch-stop layer, said sacrificial layer, or said thin film layer;

etching a second surface of said bulk substrate opposite said first surface of said bulk substrate through to said etch-stop layer using a second predetermined etching process, wherein said etching forms openings through said bulk substrate and said second predetermined etching process does not etch said etch-stop layer, said sacrificial layer or said thin film layer; and

removing said sacrificial layer using a third predetermined etching process, wherein said third predetermined etching process does not etch said bulk substrate, said etch-stop layer or said thin film layer.

4. The method of claim 3, wherein said bulk substrate comprises single crystalline silicon.

5. The method of claim 3, wherein said etch-stop layer comprises boron-doped single crystalline silicon.

6. The method of claim 3, wherein said sacrificial layer comprises silicon dioxide.

7. The method of claim 3, wherein said thin film layer comprises boron-doped polysilicon.

8. The method of claim 3, wherein said first predetermined etching process comprises a plasma etch.

9. The method of claim 3, wherein said second predetermined etching process comprises an anisotropic etch.

10. The method of claim 3, wherein said third predetermined etching process comprises a buffered hydrofluoric acid etch.

11. The method of claim 3, wherein said method utilizes only a single photolithographic mask.

12. A microfabricated containment well, comprising:

a one-piece side wall structure comprising a bulk substrate, said side wall structure having an open end;

an end face connected to said side wall structure opposite said open end, said end face comprising a microfabricated filter; and

a cavity bounded by said side wall structure and said end face.

13. The microfabricated containment well of claim 12 further comprising a substance contained within said cavity.

14. A microfabricated containment capsule, comprising:

a side wall structure comprising a one-piece bulk substrate;

at least one end face connected to said side wall structure, said end face comprising a microfabricated filter; and

a cavity bounded by said side wall structure and said at least one end face.

15. The microfabricated containment capsule of claim 14 further comprising a substance contained within said cavity.

16. A method for forming a microfabricated containment capsule, comprising the steps of:

forming a microfabricated containment well, said containment well having an open-faced cavity;

placing a substance into said cavity of said containment well;

providing a substrate; and

hermetically sealing a face of said substrate to said open end of said containment well.

17. The method of claim 16, wherein said hermetic sealing utilizes a silicone rubber glue.

18. The method of claim 16, wherein said substance is a cell, tissue or pharmaceutical composition capable of producing a desired biologically-active molecule.

19. A method for forming a microfabricated containment capsule, comprising the steps of:

forming a first microfabricated containment well and a second microfabricated containment well, each said containment well having an open-faced cavity;

placing a substance into said cavity of said first containment well; and

hermetically sealing said open end of said first containment well to said open end of said second containment well.

20. The method of claim 19, wherein said hermetic sealing utilizes a silicone rubber glue.

21. The method of claim 19, wherein said substance is a cell, tissue or pharmaceutical composition capable of producing a desired biologically-active molecule.

22. A method for forming a microfabricated containment capsule, comprising the steps of:

forming a first and a second microfabricated containment well, each said containment well having a cavity and an open end, each said containment well formed by the steps of;

providing a bulk substrate having a first surface;

forming openings in said first surface of said bulk substrate;

forming a sacrificial layer over at least part of said first surface of said bulk substrate;

forming a thin film layer over said first surface of said bulk substrate and said sacrificial layer;

forming openings through said thin film layer, wherein said openings through said thin film layer expose a portion of said sacrificial layer and are positioned relative to said openings in said bulk substrate such that said openings in said bulk substrate are at least partially blocked by said thin film structure and said openings through said thin film structure are at least partially blocked by said bulk substrate;

etching an area of a second surface of said bulk substrate opposite said first surface of said bulk substrate through to said openings in said first surface of said bulk substrate, wherein said etching forms openings through said bulk substrate; and

removing said sacrificial layer;

placing a substance into said cavity of said first containment well; and

hermetically sealing said open end of said first containment well to said open end of said second containment well.

23. The method of claim 22, wherein said hermetic sealing utilizes a silicone rubber glue.

24. The method of claim 22, wherein said substance is a cell, tissue or pharmaceutical composition capable of producing a desired biologically-active molecule.