Kind of thin films for microsystem technology and microstructuring and their use

• US 6,821,692 B1
• Filed: 02/04/1999
• Issued: 11/23/2004
• Est. Priority Date: 08/23/1996
• Status: Expired due to Fees

• Current Assignee: Alere Technologies GmbH (Abbott Laboratories Incorporated)
• Original Assignee: Alere Technologies GmbH (Abbott Laboratories Incorporated)
• Inventors: Wölfl, Stefan, Ermantraut, Eugen, Schulz, Torsten, Köhler, Johann Michael, Wohlfart, Klaus
• Primary Examiner(s): Chu, John S.
• Application Number:
  US09/230,975
• Time in Patent Office: 2,119 Days
• Field of Search: 430/17, 430/18, 430/165, 430/167, 430/191, 430/192, 430/196, 430/197
• US Class Current: 430/17
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: H01L 21/02118 carbon based polymeric organic or inorganic material, e.g. polyimides, poly cyclobutene or PVC polymers per se C08G, photoresist per se G03F
• CPC Class Codes: H01L 21/02282 liquid deposition, e.g. spin-coating, sol-gel techniques, spray coating
• CPC Class Codes: H01L 21/312 Organic layers, e.g. photoresist H01L21/3105, H01L21/32 take precedence; photoresists per se G03C

Abstract

The present invention relates to novel thin layers for microsystem techniques and microstructuring. It is an object of the invention to provide thin layers which can be manufactured under less problems and more economically than the previous conventional layers, and which permit the use of existing technologies for microstructuring. The object is realized in that the thin layer is formed of an enzymatically degradable biopolymer in a range of layer thicknesses of from 30 nm to 3 μm. Biopolymeric thin layers manufactured according to the invention permit their application, after a respective structurizing, as test assays or in setting up substance libraries.

Claims

1. A microstructurable thin layer consisting essentially of an enzymatically degradable biopolymer having an inhibitor or a competitor of the enzymatic degradability of said biopolymer on at least part of its surface, the thin layer having a thickness of 30 nm to 3 μ

m, said layer being enzymatically degradable by a suitable individual enzyme.

3. A microstructurable thin layer according to claim 1 or 2, wherein the biopolymer consists of gelatin.

2. A microstructurable thin layer consisting essentially of an enzymatically degradable biopolymer intermingled with an inhibitor or a competitor of the enzymatic degradability of said biopolymer, the thin layer having a thickness of 30 nm to 3 μ

m, said layer being enzymatically degradable by a suitable individual enzyme.

4. A microstructurable thin layer consisting essentially of an enzymatically degradable biopolymer consisting of agarose and having an inhibitor or a competitor on at least part of its surface, or said biopolymer intermingled with an inhibitor or a competitor, the thin layer having a thickness of 30 nm to 3 μ

m, said layer being enzymatically degradable by a suitable individual enzyme.

5. A microstructurable thin layer consisting essentially of an enzymatically degradable biopolymer consisting of dextrose and having an inhibitor or a competitor on at least part of its surface, or said biopolymer intermingled with an inhibitor or a competitor, the thin layer having a thickness of 30 nm to 3 μ

m, said layer being enzymatically degradable by a suitable individual enzyme.

6. A microstructurable thin layer consisting essentially of an enzymatically degradable biopolymer consisting of a lipid and having an inhibitor or a competitor on at least part of its surface, or said biopolymer intermingled with an inhibitor or a competitor, the thin layer having a thickness of 30 nm to 3 μ

m, said layer being enzymatically degradable by a suitable individual enzyme.

7. A microstructurable thin layer for microsystem technology and microstructuring consisting essentially of one degradable biopolymer enzymatically degradable by a suitable individual enzyme, the one degradable biopolymer being selected from the group consisting of gelatin, agarose, dextrose and a lipid, the biopolymer being cross-linked and combined with an inhibitor or a competitor affecting a degradation function of said individual enzyme.

8. A method for producing a structured thin layer from an enzymatically degradable biopolymeric thin layer comprising

(a) forming a biopolymeric layer comprising a biopolymer solution and a light sensitive conditioner on a substrate, said conditioner being an inhibitor of enzymatic action,

(b) exposing the biopolymeric layer to ultraviolet radiation, which causes said conditioner to be more soluble in water,

(c) separating said more soluble conditioner from the exposed biopolymeric layer, and

(d) removing the exposed biopolymeric layer by washing with an aqueous solution and an enzymatic buffer solution.

9. A method according to claim 8, in which the biopolymer consists of one selected from the group consisting of gelatin, agarose, dextrose and a lipid.

10. A method according to claim 8, in which the biopolymeric layer is applied onto the substrate by spin casting.

11. A method according to claim 10, in which the spin casting is from a solution of the biopolymer of a solids content of 1 to 30%.

12. A method according to claim 11, in which the cross-linking agent is at least one of glutaric dialdehyde and formaldehyde.

13. A method according to claim 12, in which the cross-linking agent is added to the spin casting solution in a percentage of 1 to 5%.

14. A method according to claim 9, in which the conditioner is a diazo-naphthoquinone dye, the biopolymer consists of gelatin and the enzyme in the enzymatic buffer solution is a protease.

15. A structured enzymatically degradable biopolymer thin layer produced by the method of any one of claim 8, 9, or 14.

24. A method according to claim 8, in which in (a), the biopolymer solution is applied onto the substrate and then the dye is added thereto.

25. A method according to claim 8, in which in (a), the dye is added to the biopolymer solution and then the biopolymer solution containing the dye is applied onto the substrate.

26. The method of claim 8, wherein said biopolymer is gelatin, said conditioner is a diazo-naphthoquinone dye which binds to the OH groups of the gelatin and inhibits the degradation function of a protease enzyme in a later applied buffer solution, the exposure of the biopolymer layer to ultraviolet radiation converts the diazo-naphthoquinone dye in the exposed portion of the layer to a carboxylic acid which is salified and removed from the biopolymeric layer, and the exposed portion of said layer, now free of the azo-naphthoquinone dye inhibitor, is degraded and removed by treatment with said protease enzyme buffer solution.

16. A method for producing a structured thin layer from an enzymatically degradable biopolymeric thin layer comprising:

(a) forming a layer comprising a biopolymer solution, a thermally activatable cross-linking agent, and a photoactivatable radical agent for chain prolonging or linking, on a substrate thereby to form a cross-linked biopolymeric layer on the substrate,

(b) exposing the biopolymeric layer to ultraviolet radiation, and then

(c) removing unexposed biopolymeric layer by washing with an aqueous solution and an enzymatic buffer solution.

17. A method according to claim 16 in which the biopolymer consists of one selected from the group consisting of gelatin, agarose, dextrose and a lipid.

18. A method according to claim 16 or 17, in which the layer is applied onto the substrate by spin casting.

19. A method according to claim 18, in which the spin casting is from a solution of the biopolymer of a solids content of 1 to 30%.

20. A method according to claim 16, in which the cross-linking agent is at least one of glutaric dialdehyde and formaldehyde.

21. A method according to claim 19, in which the cross-linking agent is added to the spin casting solution in a percentage of 1 to 5%.

22. A method according to claim 19, in which the biopolymer consists of gelatin and the radical agent is added to the gelatin layer in such quantity that a ratio of gelatin to radical agent is 10:

1 to 100;

1.

23. A structured enzymatically degradable biopolymer thin layer produced by the method of claim 16.

27. The method of claim 17 wherein said biopolymer is gelatin and the enzyme in said enzymatic buffer solution is a protease.