Patterning of surfaces utilizing microfluidic stamps including three-dimensionally arrayed channel networks

• US 7,267,938 B2
• Filed: 09/02/2003
• Issued: 09/11/2007
• Est. Priority Date: 05/25/2000
• Status: Expired due to Term

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Whitesides, George M., Jeon, Noo Li, Choi, Insung S., Anderson, Janelle R., Chiu, Daniel T., Ingber, Donald E., Huang, Sui, Kane, Ravindra
• Primary Examiner(s): Naff; David M.
• Application Number:
  US10/654,587
• Publication Number:
  US 20040121066A1
• Time in Patent Office: 1,470 Days
• Field of Search: None
• US Class Current: 435/4
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 2219/00382 Stamping
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00743 Cells
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 3/0258 using stamps
• CPC Class Codes: B01L 3/0262 using touch-off at substrate or container
• CPC Class Codes: B01L 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B29C 31/04 : Feeding of the material to be moulded, e.g. into a mould cavity B29C39/08 takes precedence; using a material distribution system to two or more fixed injection moulds B29C45/125
• CPC Class Codes: B29C 33/424 : Moulding surfaces provided with means for marking or patterning for injection moulding B29C45/372
• CPC Class Codes: B29C 39/10 : incorporating preformed parts or layers, e.g. casting around inserts or for coating articles coating a surface by casting in general B05D1/30, B29C39/126 takes precedence
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing
• CPC Class Codes: B81B 1/00 : Devices without movable or flexible elements, e.g. microcapillary devices
• CPC Class Codes: B81C 99/009 : Manufacturing the stamps or the moulds
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12N 11/00 : Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 33/5005 : involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: Y10S 530/81 : Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
• CPC Class Codes: Y10S 530/811 : Peptides or proteins is immobilized on, or in, an inorganic carrier
• CPC Class Codes: Y10S 530/812 : Peptides or proteins is immobilized on, or in, an organic carrier
• CPC Class Codes: Y10S 530/815 : Carrier is a synthetic polymer

Abstract

The present invention describes improved microfluidic systems and procedures for fabricating improved microfluidic systems, which contain one or more levels of microfluidic channels. The methods for fabrication the systems disclosed can provide a convenient route to topologically complex and improved microfluidic systems. The microfluidic systems can include three-dimensionally arrayed networks of fluid flow paths therein including channels that cross over or under other channels of the network without physical intersection at the points of cross over. The microfluidic networks can be fabricated via replica molding processes utilizing mold masters including surfaces having topological features formed by photolithography. The present invention also involves microfluidic systems and methods for fabricating complex patterns of materials, such as biological materials and cells, on surfaces utilizing the microfluidic systems. Specifically, the invention provides microfluidic surface patterning systems and methods for fabricating complex, discontinuous patterns on surfaces that can incorporate or deposit multiple materials onto the surfaces. The present invention also provides improved microfluidic stamps or applicators for microcontact surface patterning, which are able to pattern onto a surface arbitrary two-dimensional patterns, and which are able to pattern multiple substances onto a surface without the need for multiple steps of registration or stamping during patterning and without the need to selectively “ink” different regions of the stamp with different materials.

Claims

1. A method of patterning a material surface comprising:

providing a stamp having a structure including at least one non-linear fluid flow path therein in fluid communication with a stamping surface of the structure, the non-linear fluid flow path comprising a first channel segment thereof disposed within an interior region of the stamp structure and not completely traversing an entire thickness of the stamp structure, and a second channel segment thereof formed by an indentation disposed within the stamping surface of the structure, and said first and second segments being fluidically interconnected so fluid can flow from the first segment to the second segment;

contacting the stamping surface with a portion of the material surface; and

while maintaining the stamping surface in contact with the portion of the material surface, at least partially filling the flow path with a fluid so that at least a portion of the fluid contacts the material surface from the indentation to provide a pattern on the material surface.

2. The method of patterning a material surface as in claim 1, wherein the stamp structure comprises at least two of said non-linear fluid flow paths including a first non-linear fluid flow path and a second non-linear fluid flow path which are not fluidically interconnected, and while maintaining the stamping surface in contact with the portion of the material surface, at least partially filling each of said first and second fluid flow paths with a fluid so that at least a portion of the fluid of each of said first and second fluid flow paths contacts the material surface to provide a first pattern from fluid in the first fluid flow path and a second pattern from fluid in the second fluid flow path on the material surface.

3. The method of patterning a material surface as in claim 1, wherein the stamp is fabricated from an elastomeric material.

4. The method of patterning a material surface as in claim 3, wherein the elastomeric material comprises a silicone polymer.

5. The method of patterning a material surface as in claim 4, wherein the silicone polymer comprises poly(dimethylsiloxane).

6. The method of patterning a material surface as in claim 1, wherein the fluid comprises at least one protein, and wherein the pattern provided on the material surface is comprised of a deposited layer of the protein.

7. The method of patterning a material surface as in claim 6, wherein the at least one protein comprises a protein tending to inhibit cell adhesion to the material surface.

8. The method of patterning a material surface as in claim 7, wherein the at least one protein comprises bovine serum albumin.

9. The method of patterning a material surface as in claim 6, wherein the at least one protein comprises a protein tending to promote cell adhesion to the material surface.

10. The method of patterning a material surface as in claim 9, wherein the at least one protein comprises a protein selected from the group consisting of:

fibrinogen;

collagen;

laminin;

integrins;

antibodies;

antigens;

cell receptor proteins;

cell receptor antagonists;

combinations thereof; and

combinations of at least one of the above proteins with at least one other protein that is not a member of the group.

11. The method of patterning a material surface as in claim 1, wherein the fluid comprises a liquid containing an inorganic material, and wherein the pattern provided on the material surface is comprised of a deposited layer of the inorganic material.

12. The method of patterning a material surface as in claim 1, wherein the fluid is chemically reactive with the material surface.

13. The method of patterning a material surface as in claim 12, wherein the fluid etches at least a portion of the material surface.

14. The method of patterning a material surface as in claim 1, wherein the fluid comprises a liquid suspension of a plurality of cells, and wherein the pattern provided on the material surface is comprised of a deposited layer of cells.

15. The method of patterning a material surface as in claim 14, wherein the plurality of cells comprises a plurality of mammalian cells.

16. The method of patterning a material surface as in claim 15, wherein the mammalian cells are anchorage dependent cells.

17. The method of patterning a material surface as in claim 16, wherein the mammalian cells comprise cells selected from the group consisting of capillary endothelial cells;

tumor cells;

combinations thereof and combinations of at least one of the above cell types with at least one other cell type that is not a member of the group.

18. The method of patterning a material surface as in claim 14, further comprising, the steps of:

incubating the plurality of cells within the at least one flow path in contact with the material surface; and

allowing the cells to attach and spread onto the material surface.

19. The method of patterning a material surface as in claim 17, wherein the method is part of an in vitro assay able to determine interactions between different cell types.

20. The method of patterning a material surface as in claim 17, wherein the method is part of an in vitro assay able to determine an angiogenic potential of tumor cells.

21. The method of patterning a material surface as in claim 18, wherein the pattern produced simulates a desired tissue micro-architecture.