Process for making microneedles, microneedle arrays, masters, and replication tools

• US 8,858,807 B2
• Filed: 03/23/2007
• Issued: 10/14/2014
• Est. Priority Date: 03/24/2006
• Status: Active Grant

• Current Assignee: 3M Innovative Properties Company (3M Company)
• Original Assignee: 3M Innovative Properties Company (3M Company)
• Inventors: DeVoe, Robert J., Ferguson, Dennis E., Frederickson, Franklyn L., Johnson, Mitchell A. F., Pekurovsky, Mikhail L., Sykora, Craig R., Larsen, Jeremy K.
• Primary Examiner(s): CULBERT, ROBERTS P
• Application Number:
  US12/293,012
• Publication Number:
  US 20090099537A1
• Time in Patent Office: 2,762 Days
• Field of Search: 216/2, 216/11, 604/21, 604/22, 604/272
• US Class Current: 216/11
• CPC Class Codes: A61M 2037/0038 having a channel at the side surface
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: C08F 2/50 with sensitising agents

Abstract

A process for making a microneedle array master comprises: (a) providing a photoreactive composition, the photoreactive composition comprising: (1) at least one reactive species that is capable of undergoing an acid- or radical-initiated chemical reaction, and (2) at least one multiphoton photoinitiator system; and (b) imagewise exposing at least a portion of the composition to light sufficient to cause simultaneous absorption of at least two photons, thereby inducing at least one acid- or radical-initiated chemical reaction where the composition is exposed to the light, the imagewise exposing being carried out in a pattern that is effective to define at least the surface of a plurality of microneedles. The microneedles may be solid and the outer surface of the microneedles may be characterized by at least one concave area. The master may be used to fabricate a tool for replication.

Claims

1. A process for preparing microneedles comprising

(a) providing a photoreactive composition, said photoreactive composition comprising

(1) at least one reactive species that is capable of undergoing an acid- or radical-initiated chemical reaction, and

(2) at least one multiphoton photoinitiator system;

and

(b) imagewise exposing at least a portion of said composition to light sufficient to cause simultaneous absorption of at least two photons, thereby inducing at least one acid- or radical-initiated chemical reaction where said composition is exposed to the light, said imagewise exposing being carried out in a pattern that is effective to define at least the surface of a plurality of solid microneedles, wherein the outer surface of the microneedles is characterized by at least one concave area.

2. The process of claim 1, further comprising developing said composition by removing the resulting exposed portion, or the resulting non-exposed portion, of said composition.

3. The process of claim 1, wherein, after imagewise exposing at least a portion of said composition, said process further comprises nonimagewise exposing at least a portion of said composition to light sufficient to react at least a portion of any remaining unreacted photoreactive composition.

4. The process of claim 1 wherein said reactive species is a curable species.

5. The process of claim 1 wherein said reactive species is a non-curable species.

6. The process of claim 1 wherein said multiphoton photoinitiator system comprises photochemically effective amounts of

(a) at least one multiphoton photosensitizer capable of simultaneously absorbing at least two photons;

(b) optionally, at least one electron donor compound different from said multiphoton photosensitizer and capable of donating an electron to an electronic excited state of said photosensitizer; and

(c) at least one photoinitiator that is capable of being photosensitized by accepting an electron from an electronic excited state of said photosensitizer, resulting in the formation of at least one free radical and/or acid.

7. The process of claim 1 wherein said process comprises providing said photoreactive composition on a substrate.

8. The process of claim 1, further comprising a nonimagewise exposure carried out using a one-photon process.

9. A process for preparing a microneedle array, wherein a plurality of microneedles is prepared according to the process of claim 1, and wherein the plurality of microneedles are arranged in a microneedle array.

10. A process for preparing a replication tool, wherein a plurality of microneedles comprising a master is prepared according to the process of claim 1 and the master is used to fabricate a tool for replication.

11. A process for preparing microneedles, wherein a replication tool is prepared according to the process of claim 10, and further comprising the step of molding a polymeric plurality of microneedles with the replication tool.

12. A process for preparing a microneedle array, wherein a plurality of microneedles are prepared according to the process of claim 11, and wherein the plurality of microneedles are arranged in a microneedle array.

13. A microneedle array comprising a plurality of polymeric microneedles, the microneedle array being prepared according to a process comprising:

(a) providing a photoreactive composition, said photoreactive composition comprising;

(1) at least one reactive species that is capable of undergoing an acid- or radical-initiated chemical reaction, and

(2) at least one multiphoton photoinitiator system, wherein the multiphoton photoinitiator system comprises photochemically effective amounts of;

(a) at least one multiphoton photosensitizer that is capable of simultaneously absorbing at least two photons and that has a two-photon absorption cross-section greater than that of fluorescein;

(b) at least one electron donor compound different from the multiphoton photosensitizer and capable of donating an electron to an electronic excited state of the photosensitizer; and

(c) at least one photoinitiator that is capable of being photosensitized by accepting an electron from an electronic excited state of the photosensitizer, resulting in the formation of at least one free radical and/or acid; and

(b) imagewise exposing at least a portion of said composition to light sufficient to cause simultaneous absorption of at least two photons, thereby inducing at least one acid- or radical-initiated chemical reaction where said composition is exposed to the light, said imagewise exposing being carried out in a pattern that is effective to define at least the surface of the plurality of polymeric microneedles, wherein the outer surface of the polymeric microneedles is characterized by at least one concave area.

14. A microneedle array as claimed in claim 13, wherein at least one microneedle has an aspect ratio of between about 2:

1 and about 5;

1.

15. A microneedle array as claimed in claim 13 wherein at least one microneedle has a flared base.

16. A microneedle array as claimed in claim 13 wherein at least one microneedle comprises:

a base;

a shaft portion extending from the base to a second end distal from the base;

a microblade structure extending from the second end; and

capillary spaces associated with the microblade structure.

17. A microneedle array as claimed in claim 16 wherein the microblade structure comprises a plurality of wing members extending outwardly from a common central axis, each of the plurality of wing members having a corresponding upper edge extending from a common first end at the central axis but terminating at different second ends.

18. A microneedle array as claimed in claim 17 wherein the microblade structure comprises a first wing member having a first upper edge, a second wing member having a second upper edge and a third wing member having a third upper edge, wherein the first, second and third upper edges extend from the common first end and the first, second and third upper edges are substantially coplanar.

19. The microneedle according to claim 18 further comprising a fourth wing member having a fourth upper edge.

20. A microneedle array comprising a plurality of polymeric microneedles comprising photochemically cured compositions, the microneedle array being prepared according to a process comprising:

(a) providing a photoreactive composition, said photoreactive composition comprising;

(1) at least one reactive species that is capable of undergoing an acid- or radical-initiated chemical reaction, and

(2) at least one multiphoton photoinitiator system, wherein the multiphoton photoinitiator system comprises photochemically effective amounts of;

(a) at least one multiphoton photosensitizer that is capable of simultaneously absorbing at least two photons and that has a two-photon absorption cross-section greater than that of fluorescein;

(b) at least one electron donor compound different from the multiphoton photosensitizer and capable of donating an electron to an electronic excited state of the photosensitizer; and

(c) at least one photoinitiator that is capable of being photosensitized by accepting an electron from an electronic excited state of the photosensitizer, resulting in the formation of at least one free radical and/or acid; and

(b) imagewise exposing at least a portion of said composition to light sufficient to cause simultaneous absorption of at least two photons, thereby inducing at least one acid- or radical-initiated chemical reaction where said composition is exposed to the light, said imagewise exposing being carried out in a pattern that is effective to define at least the surface of the plurality of polymeric microneedles, wherein the outer surface of the polymeric microneedles is characterized by at least one concave area.