Integrated microneedle array and a method for manufacturing thereof

• US 8,603,384 B2
• Filed: 03/11/2009
• Issued: 12/10/2013
• Est. Priority Date: 03/11/2008
• Status: Active Grant

• Current Assignee: MyLife Technologies BV
• Original Assignee: Stichting Voor de Technische Wetenschappen, Universiteit Twente
• Inventors: van Bennekom, Joost Gerardus, Loeters, Patrick Wilhelmus Hendrikus, Winnubst, Aloysius Johannes Antonius, Lttge, Regina, Bystrova, Svetlana Nikolajevna, Domanski, Maciej, Lammertink, Rob Gerhardus Hendrikus
• Primary Examiner(s): Johnson, Christina
• Assistant Examiner(s): HUDA, SAEED M
• Application Number:
  US12/922,450
• Publication Number:
  US 20110276003A1
• Time in Patent Office: 1,735 Days
• Field of Search: 264/220, 264/225, 264/226, 264/297.8, 264/337, 264/338, 264/494, 264/496
• US Class Current: 264/337
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• 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: B81B 2201/055 Microneedles
• CPC Class Codes: B81B 2203/0361 Tips, pillars
• CPC Class Codes: B81C 2201/034 Moulding
• CPC Class Codes: B81C 99/0085 using moulds and master templates, e.g. for hot-embossing

Abstract

The invention relates to a method of manufacturing of a microneedle array comprising the steps of selecting a soft production mold comprising a set of microscopic incisions defining geometry of the microneedles, said soft production mold being capable of providing the microneedle array integrated into a base plate; using a filler material for abundantly filling the microscopic incisions of the soft production mold thereby producing the microneedle array with pre-defined geometry integrated into the base plate; wherein for the filler material a water or alcohol based ceramic or polymer-ceramic slurry is selected. The invention further relates to a microneedle array, a composition comprising a microneedle array, a system for enabling transport of a substance through a barrier and a system for measuring an electric signal using an electrode.

Claims

1. A method of manufacturing of a microneedle array comprising:

selecting a soft production mold comprising a set of microscopic incisions defining geometry of the microneedles, said soft production mold being capable of providing the microneedle array integrated into a base plate; and

using a filler material for abundantly filling the microscopic incisions of the soft production mold thereby producing the microneedle array with pre-defined geometry integrated into the base plate;

wherein for the filler material a water or alcohol based ceramic or polymer-ceramic slurry is selected, said slurry comprises alumina in 300-500 nm grain size or zirconia in 50 nm or less grain size.

2. The method according to claim 1, further comprising coating a surface of the microscopic incisions with an anti-adhesion layer for facilitating removal of the microneedle array from the soft production mold.

3. The method according to claim 1, further comprising providing one or more channels in the microneedles of the microneedle array for enabling transport of a substance through the one or more channels.

4. The method according to claim 1, comprising forming respective end portions of the microscopic incisions on an oblique surface for forming the microneedle array with oblique tips.

5. The method according to claim 1, further comprising adaptively modifying properties of the filler material by supplementing the filler material with an additive.

6. The method according to claim 5, wherein for the additive a silica-based mineral is selected.

7. The method according to claim 1, wherein the soft production mold is manufactured using a double replication of a hard master mold via in intermediate soft mold.

8. The method according to claim 7, wherein the hard master mold is manufactured by a process, said processing comprising:

disposing a first layer of a radiation sensitive material on a working surface of a Si-wafer coated with a masking layer;

processing the first layer by lithography for forming first openings in the masking layer cooperating with pre-determined crystallographic planes in the Si-wafer, said openings having pitch and width;

etching the masking layer for forming second openings cooperating with the first openings;

forming a set of cavities in the Si-wafer cooperating with the second openings;

filling the cavities with a layer of photoresist; and

generating a set of inverted microneedles, in the layer of photoresist.

9. The method according to claim 8, wherein for the masking layer Silicon Nitride layer is used.

10. The method according to claim 8, wherein for etching the masking layer reactive ion etching is used.

11. The method according to claim 8, wherein the set of cavities is formed using anisotropic wet etching using KOH.

12. The method according to claim 8, wherein a thickness of the photoresist layer filling the cavities is selected to determine a length of the resulting microneedles.

13. The method according to claim 8, further comprising modifying surface of the cavities using a silicide anti-reflection layer.

14. The method according to claim 8, further comprising:

selectively irradiating the first layer of material;

providing a second layer of a material on the selectively irradiated first layer of material; and

processing the second layer of the material together with areas of selective irradiation of the first layer for forming at least one channel in the microneedle array.

15. The method according to claim 8, wherein the inverted microneedles are generated by lithography using a mask.

16. The method according to claim 15, wherein a layout of the mask is adaptable for generating inverted microneedles having oblique tips.

17. The method according to claim 16, wherein said microneedles comprise one or more sub-sets comprising a plurality of microneedles, wherein the mask is modified for forming at least one sub-set comprising microneedles having oblique tips facing inwardly or outwardly.

18. The method according to claim 5, wherein for the additive Kaolin is selected.