Tapered hollow metallic microneedle array assembly and method of making and using the same

• US 20060084942A1
• Filed: 10/15/2004
• Published: 04/20/2006
• Est. Priority Date: 10/15/2004
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Kim, Kabseog, Lee, Jeong-Bong
• Granted Patent: US 7,627,938 B2
• Time in Patent Office: Days
• US Class Current: 604/890.100
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: Y10T 29/302 Clad or other composite foil or thin metal making
• CPC Class Codes: Y10T 29/49885 with coating before or during assembling

Abstract

The present invention includes device, system, method of using and making a microneedle array including the steps of forming one or more pins on a substrate, depositing one or more layers on the one or more pins and the substrate, exposing a portion of the one or more pins, and separating the one or more pins from the one or more layers to form the hollow microneedle array.

Claims

1. A method of making a hollow microneedle array comprising the steps of:

forming one or more pins on a substrate;

depositing one or more layers on the one or more pins and the substrate;

exposing a portion of the one or more pins; and

separating the one or more pins from the one or more layers to form the hollow microneedle array.

2. The method of claim 1, wherein the substrate is generally transparent.

3. The method of claim 1, wherein the one or more pins has a tip that is pointed, rounded, slanted, flared, tapered, blunt or combinations thereof.

4. The method of claim 1, wherein the step of exposing a portion of the one or more pins occurs on a side portion of the one or more pins.

5. The method of claim 1, wherein the step of exposing a portion of the one or more pins occurs on a tip of the one or more pins.

6. The method of claim 1, wherein the step of exposing a portion of the one or more layers comprises planarizing, laser ablation or chemical removal.

7. The method of claim 1, wherein the step of depositing one or more layers comprises electroplating, vapor deposition, spin coating, coating, sputtering, in-situ polymerization or combinations thereof.

8. The method of claim 1, wherein the one or more layers comprise a metal, a nonmetal, a polymer, a composite, a resist, a resin, a carbon nano-tube, a plastic or combinations thereof.

9. The method of claim 1, further comprising the step of applying a release layer between the one or more pins and the substrate.

10. The method of claim 1, further comprising the step of applying a release layer between the one or more pins and the one or more layers.

11. The method of claim 1, further comprising the steps of applying a resist layer to the one or more deposited layers, whereby the resist layer covers the one or more deposited layers and the substrate.

12. The method of claim 1, wherein the one or more deposited layers is a resist layer, whereby the resist layer covers the one or more deposited layers and the substrate.

13. The method of claim 1, further comprising the steps of etching the microneedle array, wherein a hollow structure remains.

14. The method of claim 1, further comprising the steps of introducing one or more agents into a portion of the microneedle array.

15. The method of claim 14 wherein the one or more agents occupy a volume of between 0.01 μ

l and 1.0 ml.

16. The method of claim 14 wherein the one or more agents is a solid, liquid or gas.

17. The method of claim 1, further comprising one or more agents disposed in, at, or about the hollow microneedle array.

18. The method of claim 17, wherein the one or more agents may be steroids, sympathomimetics, local anesthetics, antimicrobial agents, antihypertensive agents, antihypertensive diuretics, cardiotonics, coronary vasodilators, vasoconstrictors, β

-blockers, antiarrhythmic agents, calcium antagonists, anti-convulsants, agents for dizziness, tranquilizers, antipsychotics, muscle relaxants, drugs for Parkinson'"'"'s disease, respiratory agents, non-steroidal hormones, antihormones, vitamins, antitumor agents, miotics, herb medicines, antimuscarinic, muscarinic cholinergic blocking agents, mydriatics, psychic energizers, humoral agents, antispasmodics, antidepressant drugs, anti-diabetics, anorectic drugs, anti-allergenics, decongestants, antipyretics, antimigrane, anti-malarials, anti-ulcerative, peptides, anti-estrogen, anti-hormone agents, antiulcer agents, anesthetic agent, drugs having an action on the central nervous system or combinations thereof.

19. The method of claim 1, wherein the one or more layers may be bioactive agents, biodegradable, electrically conductive, thermally conductive, porous, stimulatable, or combinations thereof.

20. The method of claim 1, wherein the substrate comprises one or more bioactive agents, biodegradable, electrically conductive, thermally conductive, porous, stimulatable, or combinations thereof.

21. A product made by the method of claim 1, wherein the thickness of a wall of the microneedle is between about 10 and 20 μ

m.

22. A product made by the method of claim 1, wherein the pins may be between about 200 and 400 μ

m in height.

23. A microneedle array made by the method of claim 1.

24. The microneedle array of claim 1, having a height of between about 200 and 400 μ

m in height.

25. The method of making a hollow microneedle array comprising the steps of:

forming one or more pins on a substrate, wherein the step of forming one or more pins comprise applying a resist layers to the substrate, masking a portion of the resist layer, irradiating the resist layer, wherein the unmasked portion of the resist layer is irradiated and thus forms an optically cured resist layer, applying a second resist layer to the optically cured resist layer, wherein the second resist layer provides an area to form the one or more pins, masking a portion of the second resist layer and irradiating through the unmasked portion of the second resist layer and the backside of the cured resist layer, wherein the second resist layer is optically cure forming one or more pins in the second resist layer;

depositing one or more layers on the one or more pins and the substrate;

exposing a portion of the one or more pins; and

separating the one or more pins from the one or more layers to form the hollow microneedle array.

26. The method of claim 25, wherein the unmask portion of the resist layer is generally circular in geometry.

27. The method of claim 25, wherein the unmask portion of the resist layer is between about 20 and 120 μ

m diameter.

28. The microneedle array of claim 25, having a wall thickness of between about 10 μ

m and 20 μ

m.

29. A method of making a microneedle array comprising the steps of:

forming one or more pins on a substrate;

depositing one or more layers including a conducting portion on the one or more pins and the substrate;

exposing a portion of the one or more pins; and

separating the one or more pins from the one or more layers to form the hollow microneedle array.

30. The method of claim 29, wherein the conducting portion is a wire, molecular wire, polymer, nano-tube, inorganic compound, semiconductor particle, fiber optics or combinations thereof.

31. The method of claim 29, further comprising the steps of disposing one or more agents in or about the microneedle array.

32. The method of claim 29, wherein the filling partially is within an opening in the microneedle array.

33. The method of claim 29, wherein the one or more layers may be bioactive agents, biodegradable, electrically conductive, thermally conductive, porous, stimulatable, or combinations thereof.

34. A device for transmitting one or more agents to a patient comprising:

a microneedle array; and

one or more agents located in or about the microneedle array.

35. The device of claim 34, further comprising a delivery mechanism.

36. The device of claim 35, wherein the delivery mechanism is activated by tension, manually, shear force, diffusion, injection, pressure, electrostatic, osmosis, concentration gradients electrical magnetic field and/or low frequency ultrasound.

37. The device of claim 35, wherein the delivery mechanism is controlled by a feedback system.

38. The device of claim 34, wherein one or more agents may be delivered to the patient thought the microneedle array, wherein the one or more agents pass through the one or more needles of the microneedle array.

39. The device of claim 34, further comprising one or more agents located externally on or about the microneedle array.

40. The device of claim 34, wherein the microneedle array comprises one or more micropores, wherein the one or more agents pass through the one or more micropores to the patient.

41. The device of claim 34, wherein the microneedle array comprises one or more passageways for delivery, whereby the one or more agents pass through the one or more passageways to the patient.

42. The device of claim 34, wherein the microneedle array comprises one or more exposed portions and the one or more agents may be delivered thought the one or more exposed portions, to the patient.

43. The device of claim 34, wherein the one or more agents may be located on or about the outer surface of the one or more needles, wherein the one or more agents may be delivered to the patient.

44. The device of claim 34, wherein the one or more agents fill partially the microneedle array.

45. The device of claim 34, further comprising an actuator attached operably to the microneedle array, wherein stimulation of the actuator results in the delivery of the one or more agents to the patient.

46. The device of claim 45, wherein the actuator is operated by a tension force, a manually force, a shear force, a diffusion force, a injection, a pressure, an electrostatic charge, osmosis pressure, a concentration gradient, an electrical field, a magnetic field, a low frequency ultrasound, a high frequency sound or combinations thereof.

47. The device of claim 34, wherein the one or more agents may be steroids, respiratory agents, sympathomimetics, local anesthetics, antimicrobial agents, antihypertensive agents, antihypertensive diuretics, cardiotonics, coronary vasodilators, vasoconstrictors, β

-blockers, antiarrhythmic agents, calcium antagonists, anti-convulsants, agents for dizziness, tranquilizers, antipsychotics, muscle relaxants, drugs for Parkinson'"'"'s disease, respiratory agents, non-steroidal hormones, antihormones, vitamins, antitumor agents, miotics, herb medicines, antimuscarinic, muscarinic cholinergic blocking agents, mydriatics, psychic energizers, humoral agents, antispasmodics, antidepressant drugs, anti-diabetics, anorectic drugs, anti-allergenics, decongestants, antipyretics, antimigrane, anti-malarials, anti-ulcerative, peptides, anti-estrogen, anti-hormone agents, antiulcer agents, anesthetic agent, drugs having an action on the central nervous system or combinations thereof.

48. The device of claim 34, wherein the microneedle array comprises, one or more needles including one or more tips that may be pointed, rounded, slanted, flared, tapered blunted or combinations thereof.

49. The device of claim 34, wherein the microneedle array dissolves to deliver the one or more agents.

50. The device of claim 34, wherein the microneedle array comprises one or more needles wherein a portion of the one or more needles may be exposed on the side of the one or more needles.

51. The device of claim 34, wherein the microneedle array comprises one or more layers of a metal, an alloy, a nonmetal, a polymer, a composite, a resist, a resin, a carbon nano-tube, a nano-sheet, a semiconductor compound, a plastic or a combinations thereof.

52. The device of claim 34, wherein the microneedle array is adapted to penetrate partially a patient subcutaneously.

53. The device of claim 34, wherein the microneedle array is implanted in a host subcutaneously.

76. A method of treating a patient with one or more agents comprising administering a therapeutic agent to the patient using a microneedle array of claim 34.

54. A method of treating a patient with one or more agents comprising the step of:

contacting a microneedle array comprising one or more agents with a patent, whereby the one or more agents may be delivered to the patient.

55. The method of claim 54, wherein the substrate comprises one or more bioactive agents, biodegradable, electrically conductive, thermally conductive, porous, stimulatable, or combinations thereof.

56. The method of claim 54, wherein the microneedle array further comprises an actuator attached operably to the microneedle array to delivery the one or more agents to the patient.

57. The method of claim 54, further comprising the step of stimulating the microneedle array, whereby the stimulation of the microneedle array results in the one or more agents being delivered to the patient.

58. The method of claim 54, wherein the one or more agents may be delivered through a microneedle of the microneedle array to the patient.

59. The method of claim 54, further comprising implanting the microneedle array subcutaneously within the patient.

60. A device for administering an agent to a patient comprising:

a microneedle array having one or more hollow needles; and

an actuator attached to the microneedle array.

61. The device of claim 60, further comprising one or more agents disposed in or about the microneedle array, whereby the one or more agents may be transported to the patient.

62. A method of removing one or more materials from an area comprising the steps of:

contacting a microneedle array comprising one or more needles and one or more compartments with the area; and

withdrawing the one or more materials from the area into the one or more compartments.

63. The method of claim 62, wherein the material is blood, plasma, urine, semen, saliva, lymph fluid, meningeal fluid, amniotic fluid, glandular fluid, cerebrospinal fluid, cells, tissues, biopsy samples or combinations thereof.

64. A delivery system for one or more agents to a patient comprising:

a reservoir for containing the one or more agents; and

a microneedle array in connection with the reservoir.

65. The delivery system of claim 64, further comprising an actuator contacting the reservoir to stimulate the delivery of the one or more agents to a patient.

66. The delivery system of claim 65, wherein the actuator stimulates by surface tension, manually force, shear force, diffusion, injection, pressure, electrostatic force, osmosis, concentration gradient, electrical field, magnetic field, low frequency ultrasound, high frequency sound or combinations thereof.

67. The delivery system of claim 65, wherein the stimulation is controlled by a feedback system.

68. The delivery system of claim 65, wherein the stimulation is controlled by a processor.

69. The delivery system of claim 64, wherein the microneedle array comprises the reservoir.

70. A method of sampling a patient comprising the steps of:

contacting a microneedle array comprising a reservoir with a target; and

sampling the patient.

71. The method of claim 70, wherein the microneedle array further comprises one or more agents.

72. The method of claim 70, wherein the sampling comprises sampling blood, plasma, urine, semen, saliva, lymph fluid, meningeal fluid, amniotic fluid, glandular fluid, cerebrospinal fluid, cells, tissues, biopsy samples or combinations thereof.

73. The method of claim 70, wherein the microneedle array further comprises one or more bioactive agents, biodegradable, electrically conductive, thermally conductive, porous, stimulatable, or combinations thereof.

74. An microneedle array, comprising:

an interface region; and

one or more elongated hollow needles extending from said interface region for permitting movement of a substances therethrough, the one or more elongated hollow needles having a length of between about 200 and 400 μ

m, the one or more elongated hollow needles having at a diameter of between about 20 and 120 μ

m and the one or more elongated hollow needles a wall thickness of between about 10 and 20 μ

m.

75. The microneedle of claim 74 further including one or more agents located within said one or more elongated hollow needles for movement through the one or more elongated hollow needles.