Microneedles for minimally invasive drug delivery

• US 6,767,341 B2
• Filed: 06/13/2001
• Issued: 07/27/2004
• Est. Priority Date: 06/13/2001
• Status: Expired due to Term

• Current Assignee: ICU Medical Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Cho, Steve T.
• Primary Examiner(s): Bennett, Henry
• Assistant Examiner(s): NGUYEN, CAMTU TRAN
• Application Number:
  US09/880,377
• Publication Number:
  US 20020193754A1
• Time in Patent Office: 1,140 Days
• Field of Search: 604/20, 604/272, 604/274, 604/273, 606/167
• US Class Current: 604/272
• 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 5/150221 Valves
• CPC Class Codes: A61B 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150748 Having means for aiding positioning of the piercing device at a location where the body is to be pierced means for aiding positioning of devices for bringing media into the body A61M5/427, locating blood vessels A61B5/489
• CPC Class Codes: A61B 5/15087 short range, e.g. between console and disposable using implanted devices A61B5/150877
• 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: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/003 having a lumen
• CPC Class Codes: A61M 2037/0038 having a channel at the side surface
• 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: B81C 1/00111 Tips, pillars, i.e. raised structures microneedles A61M37/0015

Abstract

The present invention provides a microneedle incorporating a base that is broad relative to a height of the microneedle, to minimize breakage. The microneedle further includes a fluid channel and a beveled non-coring tip. Preferably arrays of such microneedles are fabricated utilizing conventional semiconductor derived micro-scale fabrication techniques. A dot pattern mask is formed on an upper surface of a silicon substrate, with each orifice of the dot pattern mask corresponding to a desired location of a microneedle. Orifices are formed that pass completely through the substrate by etching. A nitride pattern mask is formed to mask all areas in which a nitride layer is not desired. A nitride layer is then deposited on the bottom of the silicon substrate, on the walls of the orifice, and on the top of the silicon substrate around the periphery of the orifice. The nitride layer around the periphery of the orifice is offset somewhat, such that one side of the orifice has a larger nitride layer. Anisotropic etching is used to remove a substantial portion of the substrate, creating a plurality of angular, blunt, and generally pyramidal-shaped microneedles. A subsequent removal of the nitride layer, followed by an isotropic etching step, softens and rounds out the blunt angular microneedles, providing generally conical-shaped microneedles. The uneven nitride layer adjacent the orifice ensures that the microneedles will include a beveled tip. Such microneedle arrays are preferably incorporated into handheld diagnostic and drug delivery systems.

Claims

1. A hollow microneedle comprising:

(a) a generally conical-shaped body having a beveled, non-coring tip, said tip being sharp and able to pierce tissue;

(b) said conical body further having a broad base formed of a substrate at an opposite end from the tip; and

(c) a fluid channel extending through the conical-shaped body, providing fluid communication between said broad base and said tip;

(d) wherein the body has a concave curved surface defined adjacent the tip.

2. The hollow microneedle of claim 1, wherein a height of the microneedle, which is defined as a distance from said broad base to said tip, is within a range from about 50 μ

m to about 100 μ

m.

3. The hollow microneedle of claim 1, wherein a height of each microneedle, which is defined as a distance from said broad base to said tip, is substantially less than a width of said broad base.

4. The hollow microneedle of claim 1, wherein said hollow microneedle comprises silicon.

10. The hollow microneedle of claim 1, wherein the curved surface surrounds the beveled tip.

13. A hollow microneedle in accordance with claim 1, formed by a process comprising the steps of:

(a) providing a substrate comprising one of silicon and polysilicon;

(b) forming a fluid channel within said substrate, such that said fluid channel passes through said substrate;

(c) removing a substantial portion of said substrate, thereby leaving a remainder, said remainder completely circumferentially surrounding said fluid channel and defining a generally conical shape, such that said fluid channel is generally disposed along a central axis of the conical shape;

(d) wherein the step of removing a substantial portion of said substrate comprises the step of beveling a tip of said conical shape so as to form a beveled, non-coring tip for said microneedle;

(e) wherein the step of forming a fluid channel comprises the steps of;

(1) forming a first mask;

(2) etching the substrate through an orifice formed in the first mask to form said fluid channel; and

(3) removing said first mask;

(f) wherein the step of removing a substantial portion of said substrate comprises the steps of;

(1) forming a second mask;

(2) depositing a nitride layer;

(3) removing said second mask; and

(4) isotropic etching said substrate to remove a substantial portion of said substrate and to form a concave curved surface adjacent to the beveled tip.

5. Apparatus for conveying a fluid transcutaneously, comprising:

(a) a substrate, said substrate comprising at least one inlet, and a plurality of outlets in fluid communication with said at least one inlet; and

(b) a plurality of microneedles arranged in an array and extending substantially outwardly from said substrate, each microneedle including;

(i) a generally conical-shaped body having a beveled, non-coring tip, said tip being sharp and able to pierce tissue;

(ii) said conical body further having a broad base formed of the substrate at an opposite end from the tip; and

(iii) a fluid channel extending through the conical-shaped body, providing fluid communication between one of the outlets disposed said broad base is formed from the substrate and said tip;

(c) wherein the conical body has a concave curved surface defined adjacent the tip.

6. The apparatus of claim 5, wherein a height of each microneedle, which is defined as a distance from said broad base to said tip, is within a range from about 50 μ

m to about 100 μ

m.

7. The apparatus of claim 5, wherein a height of each microneedle, which is defined as a distance from said broad base to said tip, is substantially less than a width of said broad base.

8. The apparatus of claim 5, wherein at least one of said substrate and the microneedles comprises silicon.

9. The apparatus of claim 5, wherein said array of the microneedles is integrally formed from said substrate.

11. An apparatus in accordance with claim 5 produced by a process comprising the steps of:

(a) providing a silicon substrate;

(b) preparing a dotted mask on an upper surface of said silicon substrate, such that openings in said dotted mask correspond to desired locations for said hollow microneedles in the array;

(c) etching said silicon substrate so as to form a plurality of fluid channels that extend substantially through said silicon substrate;

(d) forming a nitride mask such that said nitride mask covers areas in which no nitride layer is desired;

(e) forming a nitride layer, such that said nitride layer is deposited on the substrate in the areas not covered by the nitride mask;

(f) removing said nitride mask;

(g) performing a bevel etch upon said substrate, thereby forming an array of blunt, angular microneedles;

(h) removing said nitride layer; and

(i) performing a rounding etch to round and sharpen said blunt angular microneedles, thereby completing said array of hollow microneedles.

12. The apparatus of claim 5, wherein the curved surface surrounds the beveled tip.