Microneedle devices and methods of manufacture and use thereof

• US 6,334,856 B1
• Filed: 05/21/1999
• Issued: 01/01/2002
• Est. Priority Date: 06/10/1998
• Status: Expired due to Term

• Current Assignee: Valeritas, LLC
• Original Assignee: Georgia Tech Research Corporation (University System of Georgia)
• Inventors: Cros, Florent Paul Marcel, Prausnitz, Mark R., Allen, Mark G., McAllister, Devin V.
• Primary Examiner(s): Nguyen, Anhtuan T.
• Application Number:
  US09/316,229
• Time in Patent Office: 956 Days
• Field of Search: 604/272, 604/20, 604/22, 604/35, 604/46, 604/501, 604/506, 604/181, 604/183, 604/239, 604/261, 604/191, 604/186, 298/900.1, 298/901, 424/449, 424/483, 216/75, 216/100, 216/102, 128/898
• US Class Current: 604/191
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: A61B 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• 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: A61N 1/303 Constructional details electrodes for external use A61N1/0428
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: B81B 2201/055 Microneedles
• CPC Class Codes: B81C 1/00111 Tips, pillars, i.e. raised structures microneedles A61M37/0015

Abstract

Microneedle devices are provided for transport of therapeutic and biological molecules across tissue barriers and for use as microflameholders. In a preferred embodiment for transport across tissue, the microneedles are formed of a biodegradable polymer. Methods of making these devices, which can include hollow and/or porous microneedles, are also provided. A preferred method for making a microneedle includes forming a micromold having sidewalls which define the outer surface of the microneedle, electroplating the sidewalls to form the hollow microneedle, and then removing the micromold from the microneedle. In a preferred method of use, the microneedle device is used to deliver fluid material into or across a biological barrier from one or more chambers in fluid connection with at least one of the microneedles. The device preferably further includes a means for controlling the flow of material through the microneedles. Representative examples of these means include the use of permeable membranes, fracturable impermeable membranes, valves, and pumps.

Claims

1. A method for making a microneedle device having a substrate to which a plurality of microneedles are attached or integrally formed, the method comprising

(i) forming a micromold having sidewalls which define a surface of each of the microneedles;

and

(ii) using the micromold to form the microneedles and the substrate, wherein the microneedles extend at an angle from the substrate.

2. The method of claim 1 wherein the micromold is formed by a process which includes providing a mold substrate and then forming a plurality of holes in the mold substrate, thereby forming the micromold wherein the inner surfaces of the holes define the sidewalls which correspond to outer surfaces of each of the microneedles.

3. The method of claim 2 wherein the holes are photolithographically defined.

4. The method of claim 2 wherein the holes are defined using a laser technique.

5. The method of claim 4 wherein the laser technique is laser ablation.

6. The method of claim 1 comprising, in step (ii), applying a metal, or other material having different properties than the material forming the micromold, to the sidewalls to form hollow microneedles, and then removing the micromold from the microneedles.

7. The method of claim 6 wherein the metal or other material is applied by a sputter-deposition technique or a electrodeposition technique.

8. The method of claim 6 wherein the micromold is removed using a process selected from the group consisting of oxygen plasma, thermal, solvent, aqueous, and photodegradation removal techniques.

9. The method of claim 6 wherein the metal or other material is applied by electroless plating.

10. The method of claim 1 comprising, in step (ii), filling the micromold with a fluid material that is hardened in the micromold to form the microneedles.

11. The method of claim 10 which utilizes injection molding or reaction injection molding.

12. The method of claim 1 wherein, in step (i), the micromold is fabricated by forming a mold from a mold-insert.

13. The method of claim 12 wherein the mold insert is an array of microneedles.

14. The method of claim 13 for forming hollow microneedles, comprising the steps of

(a) layering a removable material onto the array to cover the microneedles of the mold-insert,

(b) removing a part of the layer of removable material to expose the tips of the microneedles of the mold-insert, and

(c) removing the mold-insert to yield a micromold.

15. The method of claim 14 further comprising

(d) applying a metal, or other material having properties distinct from the material forming the micromold, onto the micromold to form the microneedles, and

(e) removing the micromold from the microneedles.

16. The method of claim 14 wherein the micromold is removed using a process selected from the group consisting of oxygen plasma, thermal, solvent, aqueous, and photodegradation removal techniques.

17. The method of claim 1 wherein the micromold is shaped by embossing.

20. The method of claim 1 wherein the angle is about 90°

.

21. The method of claim 2 wherein the microneedle is formed of a metal selected from the group consisting of nickel, iron, gold, titanium, copper, platinum, palladium, stainless steels, and alloys thereof.

22. The method of claim 1 wherein the micromold is formed of a polymeric material.

23. The method of claim 1 wherein the microneedles comprise a polymer.

24. The method of claim 1 wherein the micromold formed in step (i) is in the form of an array of mold microneedles, wherein the outer surfaces of each of the mold microneedles correspond to the sidewalls which define the inner surface of hollow microneedles;

and

wherein, in step (ii), the array is coated with a material forming the microneedles and the substrate of the device, and then the micromold is removed.

18. The method of 1 wherein the micromold is shaped using a laser to selectively remove material.

19. The method of claim 18 wherein the material is a polymer/metal laminante.