System and method for drug delivery and microfluidic applications using microneedles

• US 20060030812A1
• Filed: 05/20/2005
• Published: 02/09/2006
• Est. Priority Date: 08/05/2004
• Status: Active Grant

• Current Assignee: Apogen Technologies Incorporated (Perspecta, Inc.)
• Original Assignee: Apogen Technologies Incorporated (Perspecta, Inc.)
• Inventors: Golubovic-Liakopoulos, Nevenka, Fricano, Glenn, Danielson, Michael
• Granted Patent: US 7,560,036 B2
• Time in Patent Office: Days
• US Class Current: 604/46
• 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, the method comprising the steps of:

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

apply photoresist to the one or more protective layers;

removing at least a portion of the one or more protective layers;

removing the photoresist; and

anisotropically etching the front surface of the substrate to form one or more microneedles in 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,

wherein the bases of the one or more microneedles are integrally formed of the substrate and the tips are sufficiently sharp to penetrate 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 comprises forming at least one oxide layer.

4. The method of claim 1 wherein the step of forming one or more protective layers 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 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 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 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 substrate to form the one or more microneedles comprises etching the substrate using TMAH etching.

9. The method of claim 1 further comprising a step of removing the one or more protective layers.

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

12. The method of claim 11 wherein at least one of the substances to be administered to the patient is incorporated into a polymeric material.

13. The method of claim 1 further comprising a step of forming one or more holes in the substrate that extend from the back surface of the substrate to the front surface of the substrate.

14. The method of claim 1 further comprising a step of forming one or more holes on the back surface of the substrate corresponding to a position of at least one of the microneedles.

15. The method of claim 14 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.

16. The method of claim 14 wherein the step of forming the one or more holes on the back surface of the substrate comprises the steps of:

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

apply photoresist to the one or more protective layers;

removing at least a portion of the one or more protective layers;

removing the photoresist; and

etching the back surface of the substrate to form one or more holes corresponding to a position of at least one of the microneedles.

17. The method of claim 16 wherein the step of etching the back surface of the substrate to form one or more holes comprises anisotropically etching 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, the conical holes having a plurality of internal surfaces formed by the etching.

18. The method of claim 16 further comprising a step of 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.

19. The method of claim 16 wherein the step of forming one or more protective layers comprises forming at least one oxide layer.

20. The method of claim 16 wherein the step of forming one or more protective layers comprises forming at least one silicon nitride layer.

21. The method of claim 16 wherein the step of etching the one or more protective layers comprises etching the one or more protective layers using reactive ion etching.

22. The method of claim 16 wherein the step of etching the back surface of the substrate comprises etching the substrate using KOH etching.

23. The method of claim 16 wherein the step of etching the back surface of the substrate comprises etching the substrate using TMAH etching.

24. The method of claim 16 further comprising a step of removing the one or more protective layers.

25. A microneedle array formed by the method of claim 1.

71. The method of claim 16 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 the one or more microneedles, thereby creating at least one opening on the surface of the microneedle.

26. A drug delivery device comprising:

a substrate having a back surface and a front surface;

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.

27. The drug delivery device of claim 26 wherein at least one of the substances operable to be administered to the patient is incorporated into a polymeric material.

28. The drug delivery device of claim 26 wherein at least one of the substances operable to be administered to the patient is a time-release substance.

29. The drug delivery device of claim 26 wherein one or more holes extend from the back surface of the substrate to the front surface of the substrate.

30. The drug delivery device of claim 26 wherein one or more holes extend from the back surface of the substrate to the surfaces of the one or more microneedles.

31. The drug delivery device of claim 26 wherein one or more conical holes extend from the back surface of the substrate into the bodies of the one or more microneedles, the conical holes having a plurality of internal surfaces.

32. The drug delivery device of claim 31 wherein one or more holes extend from the internal surfaces of the one or more conical holes to the surfaces of the one or more microneedles.

33. The drug delivery device of claim 26 wherein the substrate is comprised of a silicon wafer.

72. The drug delivery device of claim 26 wherein a lateral groove extends from the back surface of the substrate into the bodies of the one or more microneedles, thereby creating at least one opening on the surface of the microneedle.

34. A method of administering one or more substances to a patient comprising the steps of:

penetrating at least an outer layer of the skin of the patient with one or more microneedles extending from a front surface of a substrate, at least one of the microneedles being coated with one or more substances to be administered to the patient; and

releasing at least one of the substances into the patient,

wherein the microneedles have a generally conical-shaped body defined by a plurality of surfaces sloping upwards from a relatively broad base to a tip.

35. The method of claim 34 wherein the substrate is comprised of a silicon wafer.

36. The method of claim 34 wherein at least one of the substances is incorporated into a polymeric material.

37. The method of claim 34 wherein at least one of the substances is a time-release substance.

38. The method of claim 37 further comprising a step of leaving at least one of the microneedles within the patient for a sufficient period of time to allow the at least one time-release substance to be released into the patient.

39. The method of claim 34 further comprising a step of transferring one or more substances from the back surface of the substrate to the front surface of the substrate through one or more holes that extend from the back surface of the substrate to the front surface of the substrate.

40. The method of claim 34 further comprising a step of transferring one or more substances from the back surface of the substrate through 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.

41. The method of claim 34 further comprising a step of abrading the outer layer of the skin of the patient with the microneedles prior to the step of penetrating.

42. A method of administering one or more substances to a patient comprising the steps of:

penetrating at least an outer layer of the skin of the patient with one or more microneedles extending from a front surface of a substrate, at least one of the microneedles having one or more holes extending from a back surface of the substrate to a surface of the at least one microneedle, and

transferring one or more substances from the back surface of the substrate through the one or more holes extending from the back surface of the substrate to the surface of the at least one microneedle and into the patient,

wherein the microneedles have a generally conical-shaped body defined by a plurality of surfaces sloping upwards from a relatively broad base to a tip.

43. The method of claim 42 wherein at least one of the microneedles is coated with one or more substances to be administered to the patient.

44. The method of claim 43 wherein at least one of the one or more substances coated onto at least one of the microneedles is incorporated into a polymeric material.

45. The method of claim 43 further comprising a step of releasing at least one of the substances coated onto at least one of the microneedles into the patient.

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

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;

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

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

anisotropically etching the front surface of the substrate to form one or more microneedles in 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,

wherein the bases of the one or more microneedles are integrally formed of the substrate and the tips are sufficiently sharp to penetrate an outer layer of the skin of a patient.

47. The method of claim 46 wherein the substrate is comprised of a silicon wafer.

48. The method of claim 46 wherein the step of forming one or more protective layers comprises forming at least one oxide layer.

49. The method of claim 46 wherein the step of forming one or more protective layers comprises forming at least one silicon nitride layer.

50. The method of claim 46 wherein the step of removing at least a portion of the one or more protective layers comprises the step of performing photolithography on the front surface of the substrate to form a footprint for the microneedle array.

51. The method of claim 46 wherein the step of removing at least a portion of the one or more protective layers comprises the step of etching the one or more protective layers using reactive ion etching.

52. The method of claim 46 wherein the step of anisotropically etching the substrate to form the one or more microneedles comprises etching the substrate using KOH etching.

53. The method of claim 46 wherein the step of anisotropically etching the substrate to form the one or more microneedles comprises etching the substrate using TMAH etching.

54. The method of claim 46 further comprising a step of removing the one or more protective layers.

55. The method of claim 46 further comprising a step of 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.

56. The method of claim 46 further comprising a step of coating at least one of the microneedles with one or more substances to be administered to a patient through the skin.

57. The method of claim 56 wherein at least one of the substances to be administered to the patient is incorporated into a polymeric material.

58. The method of claim 46 further comprising a step of forming one or more holes in the substrate that extend from the back surface of the substrate to the front surface of the substrate.

59. The method of claim 46 further comprising a step of forming one or more holes on the back surface of the substrate corresponding to a position of at least one of the microneedles.

60. The method of claim 59 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.

61. The method of claim 59 wherein the step of forming the one or more holes on the back surface of the substrate comprises the steps of:

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

apply photoresist to the one or more protective layers;

removing at least a portion of the one or more protective layers;

removing the photoresist; and

etching the back surface of the substrate to form one or more holes corresponding to a position of at least one of the microneedles.

62. The method of claim 61 wherein the step of etching the back surface of the substrate to form one or more holes comprises anisotropically etching 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, the conical holes having a plurality of internal surfaces formed by the etching.

63. The method of claim 61 further comprising a step of 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.

64. The method of claim 61 wherein the step of forming one or more protective layers comprises forming at least one oxide layer.

65. The method of claim 61 wherein the step of forming one or more protective layers comprises forming at least one silicon nitride layer.

66. The method of claim 61 wherein the step of etching the one or more protective layers comprises etching the one or more protective layers using reactive ion etching.

67. The method of claim 61 wherein the step of etching the back surface of the substrate comprises etching the substrate using KOH etching.

68. The method of claim 61 wherein the step of etching the back surface of the substrate comprises etching the substrate using TMAH etching.

69. The method of claim 61 further comprising a step of removing the one or more protective layers.

70. A microneedle array formed by the method of claim 46.

73. The method of claim 61 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 the one or more microneedles, thereby creating at least one opening on the surface of the microneedle.