System and method for drug delivery and microfluidic applications using microneedles

• US 7,560,036 B2
• Filed: 05/20/2005
• Issued: 07/14/2009
• Est. Priority Date: 08/05/2004
• Status: Expired due to Fees

• Current Assignee: Apogen Technologies Incorporated (Perspecta, Inc.)
• Original Assignee: Apogen Technologies Incorporated (Perspecta, Inc.)
• Inventors: Fricano, Glenn, Danielson, Michael, Golubovic-Liakopoulos, Nevenka
• Primary Examiner(s): OLSEN, ALLAN W
• Application Number:
  US11/133,245
• Publication Number:
  US 20060030812A1
• Time in Patent Office: 1,516 Days
• Field of Search: None
• US Class Current: 216/2
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61B 2017/00526 Methods of manufacturing
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B81B 2201/055 Microneedles
• CPC Class Codes: B81C 1/00111 Tips, pillars, i.e. raised structures microneedles A61M37/0015

Abstract

The invention relates to a method of fabricating a microneedle array in a substrate, a drug delivery device comprising one or more microneedles extending upwards from the front surface of the substrate, the microneedles having a generally conical-shaped body defined by a plurality of surfaces sloping upwards from a relatively broad base to a tip, and one or more substances coating the microneedles, the one or more substances being operable to be administered to a patient, wherein the tips of the one or more microneedles are sufficiently sharp to penetrate an outer layer of the skin of the patient, and a method of administering one or more substances to a patient using the device.

Claims

1. A method of fabricating a microneedle array in a substrate having a front surface and a back surface, comprising:

forming one or more protective layers on the front surface of the substrate;

applying photoresist to the one or more protective layers on the front surface of the substrate;

removing at least a portion of the one or more protective layers from the front surface of the substrate;

removing the photoresist from the front surface of the substrate;

anisotropically etching the front surface of the substrate to form one or more microneedles in the substrate, said microneedles having a conical-shaped body defined by a plurality of surfaces sloping upwardly from a base to a tip;

forming one or more protective layers on the back surface of the substrate;

applying photoresist to the one or more protective layers on the back surface of the substrate;

removing a least a portion of the one or more protective layers from the back surface of the substrate;

removing the photoresist from the back surface of the substrate; and

etching anisotropically one or more conical holes in the substrate such that at least one of the conical holes extends from the back surface of the substrate into the body of the one or more microneedles, wherein the conical holes have a plurality of internal surfaces formed by the etching;

wherein the bases of the one or more microneedles are formed integrally with the substrate and the tips of the one or more microneedles are capable of penetrating an outer layer of the skin of a patient.

2. The method of claim 1 wherein the substrate is comprised of a silicon wafer.

3. The method of claim 1 wherein the step of forming one or more protective layers on the front surface of the substrate comprises forming at least one oxide layer.

4. The method of claim 1 wherein the step of forming one or more protective layers on the front surface of the substrate comprises forming at least one silicon nitride layer.

5. The method of claim 1 wherein the step of removing at least a portion of the one or more protective layers from the front surface of the substrate comprises the step of performing photolithography on the front surface of the substrate to form a footprint for the microneedle array.

6. The method of claim 1 wherein the step of removing at least a portion of the one or more protective layers from the front surface of the substrate comprises the step of etching the one or more protective layers using reactive ion etching.

7. The method of claim 1 wherein the step of anisotropically etching the front surface of the substrate to form the one or more microneedles comprises etching the substrate using KOH etching.

8. The method of claim 1 wherein the step of anisotropically etching the front surface of the substrate to form the one or more microneedles comprises etching the front surface of the substrate using TMAH etching.

9. The method of claim 1, and further comprising removing the one or more protective layers from the front surface of the substrate.

10. The method of claim 1, and further comprising removing at least a portion of the substrate located above the surface of the substrate immediately adjacent to the bases of the one or more microneedles.

11. The method of claim 1, and further comprising forming one or more holes in the substrate that extend from the back surface of the substrate to the front surface of the substrate.

12. The method of claim 1 wherein the step of forming one or more conical holes on the back surface of the substrate comprises forming one or more conical holes that extend from the back surface of the substrate to at least one of the surfaces of the one or more microneedles.

13. The method of claim 1, and further comprising forming one or more holes through the substrate extending from at least one of the surfaces of the one or more conical holes to the surfaces of the one or more microneedles.

14. The method of claim 1 wherein the step of forming one or more protective layers on the back surface of the substrate comprises forming at least one oxide layer on the back surface of the substrate.

15. The method of claim 1 wherein the step of forming one or more protective layers on the back surface of the substrate comprises forming at least one silicon nitride layer on the back surface of the substrate.

16. The method of claim 1 wherein the step of removing at least a portion of the one or more protective layers on the back surface of the substrate comprises etching the one or more protective layers on the back surface of the substrate using reactive ion etching.

17. The method of claim 1 wherein the step of etching the back surface of the substrate comprises etching the back surface of the substrate using KOH etching.

18. The method of claim 1 wherein the step of etching the back surface of the substrate comprises etching the back surface of the substrate using TMAH etching.

19. The method of claim 1, and further comprising removing the one or more protective layers from the back surface of the substrate.

20. The method of claim 1 wherein the step of etching the back surface of the substrate to form one or more holes comprises etching a lateral groove in the substrate such that the tip of the lateral groove extends from the back surface of the substrate into the body of one or more microneedles, thereby creating at least one opening on the surface of the microneedle.

21. The method of claim 1, and further comprising coating at least one of the microneedles with one or more substances to be administered to a patient through the skin.

22. The method of claim 21 wherein at least one of the substances to be administered to the patient is incorporated into a polymeric material.

23. A method of fabricating a microneedle array in a substrate having a front surface and a back surface, comprising:

forming one or more protective layers on the front surface of the substrate;

removing at least a portion of the one or more protective layers from the front surface of the substrate;

etching anisotropically the front surface of the substrate to form an offset portion in the substrate;

removing an additional portion of at least one or more protective layers;

etching anisotropically the front surface of the substrate to form one or more microneedles in the substrate, wherein the microneedles have a conical-shaped body defined by a plurality of surfaces sloping upwardly from a base to a tip;

forming one or more protective layers on the back surface of the substrate;

applying photoresist to the one or more protective layers on the back surface of the substrate;

removing at least a portion of the one or more protective layers from the back surface of the substrate;

removing the photoresist; and

etching anisotropically one or more conical holes in the back surface of the substrate corresponding to a position of at least one of the microneedles such that at least one of the conical holes extends from the back surface of the substrate into the body of the one or more microneedles, wherein the conical holes have a plurality of internal surfaces formed by the etching, and

wherein the bases of the one or more microneedles are formed integrally with the substrate and the tips of the one or more microneedles are capable of penetrating an outer layer of the skin of a patient.

24. The method of claim 23 wherein the substrate is comprised of a silicon wafer.

25. The method of claim 23 wherein the step of forming one or more protective layers on the front surface of the substrate comprises forming at least one oxide layer.

26. The method of claim 23 wherein the step of forming one or more protective layers on the front surface of the substrate comprises forming at least one silicon nitride layer.

27. The method of claim 23 wherein the step of removing at least a portion of the one or more protective layers from the front surface of the substrate comprises the step of performing photolithography on the front surface of the substrate to form a footprint for the microneedle array.

28. The method of claim 23 wherein the step of removing at least a portion of the one or more protective layers from the front surface of the substrate comprises the step of etching the one or more protective layers using reactive ion etching.

29. The method of claim 23 wherein the step of anisotropically etching the front surface of the substrate to form the one or more microneedles comprises etching the front surface of the substrate using KOH etching.

30. The method of claim 23 wherein the step of anisotropically etching the front surface of the substrate to form the one or more microneedles comprises etching the front surface of the substrate using TMAH etching.

31. The method of claim 23, and further comprising removing the one or more protective layers from the front surface of the substrate.

32. The method of claim 23, and further comprising removing at least a portion of the substrate located above the surface of the substrate immediately adjacent to the bases of the one or more microneedles.

33. The method of claim 23 wherein the step of forming one or more holes on the back surface of the substrate comprises forming one or more holes that extend from the back surface of the substrate to at least one of the surfaces of the one or more microneedles.

34. The method of claim 23, and further comprising forming one or more holes through the substrate extending from at least one of the surfaces of the one or more conical holes to the surfaces of the one or more microneedles.

35. The method of claim 23 wherein the step of forming one or more protective layers on the back surface of the substrate comprises forming at least one oxide layer.

36. The method of claim 23 wherein the step of forming one or more protective layers on the back surface of the substrate comprises forming at least one silicon nitride layer.

37. The method of claim 23 wherein the step of removing at least a portion of the one or more protective layers on the back surface of the substrate comprises etching the one or more protective layers on the back surface of the substrate using reactive ion etching.

38. The method of claim 23 wherein the step of etching the back surface of the substrate comprises etching the back surface of the substrate using KOH etching.

39. The method of claim 23 wherein the step of etching the back surface of the substrate comprises etching the back surface of the substrate using TMAH etching.

40. The method of claim 23, and further comprising removing the one or more protective layers from the back surface of the substrate.

41. The method of claim 23 wherein the step of etching the back surface of the substrate to form one or more holes comprises etching a lateral groove in the substrate such that the tip of the lateral groove extends from the back surface of the substrate into the body of one or more microneedles, thereby creating at least one opening on the surface of the microneedle.

42. The method of claim 23 and further comprising coating at least one of the microneedles with one or more substances to be administered to a patient through the skin.

43. The method of claim 42 wherein at least one of the substances to be administered to the patient is incorporated into a polymeric material.