Intracutaneous microneedle array apparatus

• US 6,379,324 B1
• Filed: 06/09/1999
• Issued: 04/30/2002
• Est. Priority Date: 06/09/1999
• Status: Expired due to Term

• Current Assignee: Corium, Inc.
• Original Assignee: The Procter & Gamble Company
• Inventors: Sherman, Faiz Feisal, Gartstein, Vladimir, Owens, Grover David, Yuzhakov, Vadim Vladimirovich, Nebrigic, Dragan Danilo
• Primary Examiner(s): Casler, Brian L.
• Assistant Examiner(s): THISSELL, JEREMY
• Application Number:
  US09/328,947
• Time in Patent Office: 1,056 Days
• Field of Search: 604/20-22, 604/19
• US Class Current: 604/22
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150099 by negative pressure, other than vacuum extraction into a syringe by pulling on the piston rod or into pre-evacuated tubes
• CPC Class Codes: A61B 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150389 Hollow piercing elements, e.g. canulas, needles, for piercing the skin
• CPC Class Codes: A61B 5/150412 Pointed piercing elements, e.g. needles, lancets for piercing the skin blade-like piercing elements A61B5/150442
• CPC Class Codes: A61B 5/150458 Specific blade design, e.g. for improved cutting and penetration characteristics
• CPC Class Codes: A61B 5/150969 Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• 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: B29L 2031/7544 Injection needles, syringes
• CPC Class Codes: B29L 2031/756 Microarticles, nanoarticles
• CPC Class Codes: B81B 2201/055 Microneedles
• CPC Class Codes: B81C 99/0085 using moulds and master templates, e.g. for hot-embossing

Abstract

A first embodiment microneedle array is constructed of silicon and silicon dioxide compounds using MEMS technology and standard microfabrication techniques to create hollow cylindrical individual microneedles. The resulting array of microneedles can penetrate with a small pressure through the stratum corneum of skin to either deliver drugs or to facilitate interstitial fluid sampling through the hollow microneedles into the epidermis. The delivery of drugs and sampling of fluids can be performed by way of passive diffusion (time release), instantaneous injection, or iontophoresis. In a second embodiment, an array of hollow (or solid) microneedles is constructed of plastic or some other type of molded or cast material. An electric field may be used to increase transdermal flow rate, and the microneedles can be effectively combined with the application of an electric field between an anode and cathode attached to the skin which causes a low-level electric current. As a drug delivery system, the microneedle array includes electrodes that apply an electric potential to the skin between the electrode locations. One of the electrode assemblies is filled with an ionized drug, and the charged drug molecules move into the body due to the applied electric potential. As a body-fluid sampling system, the microneedle array also includes electrodes to assist in moving fluid from the body into a receiving chamber, and which further includes a bioelectrochemical sensor to measure the concentration of a particular substance.

Claims

1. A structure comprising a base element and plurality of microneedles formed thereon, wherein said base element has a first side and a second side;

wherein said plurality of microneedles comprises a plurality of hollow elements which project from the second side of said base element along a longitudinal axis that is at an angle with respect to said base element;

wherein at least one of said longitudinal axes of said microneedles is in alignment with one of a plurality of first openings in the second side of said base element;

wherein said hollow elements of said plurality of microneedles allow liquid to flow therethrough between a plurality of second openings at a distal end of said hollow elements and said first openings at the second side of said base element; and

a container structure comprising;

(a) a reservoir capable of holding a liquid,

(b) a first electrode proximal to said reservoir,

(c) an electrical power source that is in communication with said electrode, and

(d) a second electrode proximal to said reservoir at a location different than said first electrode, said second electrode detecting an electrical signal in the manner of a bioelectrochemical sensor.

2. The structure as recited in claim 1, wherein said hollow elements are tubular in shape.

3. The structure as recited in claim 1, wherein said hollow elements are conical in shape.

4. The structure as recited in claim 1, wherein said first or said second electrode of said container structure facilitates dispensing an ionized liquid from said reservoir through said plurality of microneedles into skin by iontophoresis.

5. The structure as recited in claim 1, further comprising an electronic controller;

wherein said first or said second electrode facilitates body-fluid sampling of a body fluid from skin through said plurality of microneedles by reverse iontophoresis.

6. The structure as recited in claim 1, wherein said signal detected by said second electrode provides an indication of a concentration of a sampled body-fluid.

7. A structure comprising a base element and plurality of microneedles formed thereon, wherein said base element has a first side and a second side;

wherein said plurality of microneedles comprises a plurality of solid projections which extend from the second side of said base element along a longitudinal axis that is at an angle with respect to said base element; and

wherein at least one of said longitudinal axes of said microneedles is located proximal to a plurality of openings in the second side of said base element, such that there are individual of said openings near each one of said projections; and

wherein said plurality of microneedles allows liquid to flow along their outer surfaces through said openings at the second side of said base element; and

a container structure comprising;

(a) a reservoir capable of holding a liquid, (b) an electrode proximal to said reservoir, and (c) an electrical power source that is in communication with said electrode.

8. The structure as recited in claim 7, wherein said openings are smaller in cross-section than said solid projections.

9. The structure as recited in claim 7, wherein there is at least one of said openings for each of said plurality of projections.

10. The structure as recited in claim 7, wherein the electrode of said container structure facilitates dispensing an ionized liquid from said reservoir through said plurality of microneedles into skin by iontophoresis.

11. The structure as recited in claim 10, further comprising an external liquid storage tank that is in fluidic communication with said reservoir, and a fluid channel structure that transports liquid from said external liquid storage tank to said reservoir.

12. The structure as recited in claim 7, further comprising an electronic controller;

wherein said electrode facilitates body-fluid sampling of a body fluid from skin through said plurality of microneedles by reverse iontophoresis.

13. The structure as recited in claim 12, further comprising a second electrode proximal to said reservoir at a location different than said first electrode, said second electrode detecting an electrical signal in the manner of a bioelectrochemical sensor.

14. The structure as recited in claim 13, wherein said the signal detected by said second electrode provides an indication of a percentage concentration of a sampled body-fluid.

15. The structure as recited in claim 12, wherein said electrical power source includes a battery, and said electronic controller includes a central processing circuit;

and further comprising a visual indicator.

16. An integral structure comprising a base element and plurality of microneedles formed thereon, wherein said base element has a first side and a second side;

said plurality of microneedles comprising a plurality of solid projections which extend from the second side of said base element along longitudinal axes that are at an angle with respect to said base element; and

a first plurality of openings in the second side of said base element, such that there are individual of said openings near each one of said projections, said openings being of a sufficient size so as to allow liquid to flow therethrough.

17. The structure as recited in claim 16, wherein said liquid passes from said first plurality of openings at the second side of said base element and into skin, by way of diffusion.

18. The structure as recited in claim 16, further comprising:

(a) a reservoir for holding a liquid that is to be dispensed, (b) an electrode proximal to said reservoir at a first location, and (c) an electrical power source that is in communication with said electrode;

wherein said electrode facilitates dispensing said liquid into skin by iontophoresis.

19. The structure as recited in claim 16, further comprising:

(a) a reservoir for holding a liquid that is to be sampled,

(b) a first electrode proximal to said reservoir at a first location,

(c) a second electrode proximal to said reservoir at a second location which detects an electrical signal in the manner of a bioelectrochemical sensor,

(d) an electrical power source that is in communication with said first electrode, and

(e) an electronic controller;

wherein said first electrode facilitates body-fluid sampling of a body fluid from skin by reverse iontophoresis.

20. The structure as recited in claim 16, wherein said microneedles exhibit a length along said longitudinal axis in the range of 100 microns through 200 microns.

21. The structure as recited in claim 16, wherein said microneedles exhibit a length along said longitudinal axis in the range of 1 microns through 5 microns.

22. The structure as recited in claim 16, wherein said microneedles exhibit an inner diameter in the range of 1-49 microns.

23. The structure as recited in claim 16, wherein said microneedles exhibit an outer diameter in the range of 1-50 microns.

24. The structure as recited in claim 16, further comprising:

(a) a reservoir for holding a liquid that is to be dispensed,

(b) a pressure source that is in communication with said reservoir;

wherein said pressure source facilitates dispensing said liquid along the surface of said plurality of microneedles into skin by applying a fluidic pressure thereto.

25. The structure as recited in claim 16, wherein said plurality of microneedles allows liquid to flow along their outer surfaces through said first plurality of openings at the second side of said base element.