Method and/or apparatus for puncturing a surface for extraction, in situ analysis, and/or substance delivery using microneedles

• US 20050171480A1
• Filed: 11/22/2004
• Published: 08/04/2005
• Est. Priority Date: 11/21/2003
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Smith, Rosemary L., Mukerjee, Erik V.
• Granted Patent: US 7,753,888 B2
• Time in Patent Office: Days
• US Class Current: 604/173
• 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 5/150282 for piercing elements, e.g. blade, lancet, canula, needle
• CPC Class Codes: A61B 5/150297 for piercing devices, i.e. devices ready to be used for lancing or piercing for piercing elements A61B5/150282, for driving devices A61B5/15029
• CPC Class Codes: A61B 5/150343 Collection vessels for collecting blood samples from the skin surface, e.g. test tubes, cuvettes sampling from within body cavities A61B5/150015, A61B5/150045
• 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 5/150969 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 5/15105 Purely manual piercing, i.e. the user pierces the skin without the assistance of any driving means or driving devices
• CPC Class Codes: A61B 5/15142 Devices intended for single use, i.e. disposable
• 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: B81B 2201/055 Microneedles
• CPC Class Codes: B81C 1/00111 Tips, pillars, i.e. raised structures microneedles A61M37/0015

Abstract

A method and apparatus for puncturing a surface for extraction, in situ monitoring, and/or substance delivery uses microneedles with improved properties. Applications include easy to handle glucose monitoring using a group of hollow out-of-plane silicon microneedles to sample substances in interstitial fluid from the epidermal skin layer.

Claims

1. A microneedle comprising:

a needle shaft with a substantially solid tip, said shaft extending substantially vertically above a needle base; and

an opening nearer to said base;

such that said tip can puncture a surface in order to deliver or sample fluids with reduced blockage of said opening, said opening being substantially distant from said solid tip.

2. The device of claim 1 further comprising:

said needle shaft is between about 100 to 5000 micrometers in height.

3. The device of claim 1 further comprising:

said needle shaft is between about 100 to 450 micrometers in height.

4. The device of claim 1 further comprising:

said opening is located 20% below said tip on said needle shaft height.

5. The device of claim 1 further comprising:

said opening is surrounded on all sides beginning at least 40% below said tip on said needle shaft height.

6. The device of claim 1 further comprising:

said opening is surrounded on all sides beginning at least 60% below said tip on said needle shaft height.

7. The device of claim 1 further comprising:

said opening is surrounded on all sides beginning at least 90% below said tip on said needle shaft height.

8. The device of claim 1 further comprising:

said substianially solid tip comprises at least 20% of said needle shaft height.

9. The device of claim 1 further comprising:

said substianially solid tip comprises at least 40% of said needle shaft height.

10. The device of claim 1 further comprising:

said substianially solid tip comprises at least 60% of said needle shaft height.

11. The device of claim 1 further comprising:

said substianially solid tip comprises at least 80% of said needle shaft height.

12. The device of claim 1 further comprising:

a groove that runs along said shaft nearer said tip and terminates into said opening.

13. The device of claim 1 further comprising:

a substrate in contact with said base, said substrate providing support for said base, said hole extending into to said substrate to connect with one or more microchannels in said substrate.

14. The device of claim 1 further comprising:

a compensation structure between an underside hole of said needle and a channel floor, said structure easing fluid flow.

15. The device of claim 1 further comprising:

said opening is formed by etching.

16. The device of claim 1 further comprising:

said opening is formed by laser ablation.

17. The device of claim 1 further comprising:

said opening is formed using a mold.

18. The device of claim 1 further comprising:

said opening is formed using a drill.

19. A method of forming a microneedle on a wafer comprising:

forming a first hole into a first side of a said wafer, said hole being roughly parallel with the thinnest dimension of said wafer;

forming a second narrower hole into a second side of a said wafer, said second hole being roughly parallel with the smallest dimension of said wafer;

said second hole being roughly aligned with said first hole and operatively connecting with said first hole;

defining a column in said wafer on said second side roughly around said second hole by removing portions of said wafer to a desired depth; and

isotropically etching said columns on said second side of said wafer to form a vertical axial surface around said second hole, said vertical axial surface having an isotropic etch cross-sectional profile between an external end of said second hole and a base of said wafer.

20. The method of claim 19 further wherein:

said defining is performed using a deep reactive etch.

21. The method of claim 19 further wherein:

said defining is performed using a saw.

22. The method of claim 19 further comprising:

alternating said isotropic etching between an agitated and a quiescent phase to thin and sharpen said column into said microneedle.

23. The method of claim 19 further wherein:

said needle shank heights are greater than about 150 to 400 micrometers.

24. The method of claim 19 further wherein:

said smaller holes are etched into said wafer to at least a depth of about between 110 to 230 micrometers.

25. The method of claim 19 further wherein:

said larger holes are etched into said wafer to a at least a depth of about between 300 to 420 micrometers.

26. The method of claim 19 further wherein:

said microneedle size, density and shape are controlled by a series of independent fabrication steps, such that using the same series of fabrication steps and photolithographic masks, a wide range of needle sizes and shapes can be built for different applications.

27. The method of claim 19 further wherein:

different needle tip shapes can be produced by changing a relative positioning of said second hole to a shaft of said micro needle.

28. The method of claim 19 further wherein:

different needle tip shapes can be produced by changing the relative positioning of said second hole to outer walls of said column prior to said isotropic etching.

29. The method of claim 19 further wherein:

said microneedle has a snake fang shape, which is achieved by positioning said second hole about 50-75% from said column'"'"'s center.

30. The method of claim 19 further wherein:

said micro-needle has a nearly solid tip for at least 35% of said shaft height.

31. The method of claim 19 further wherein:

said microneedle is one of a plurality of microneedles formed from an etchable material selected from a group consisting of;

glass, aluminum, a semiconductor material, gallium arsinide, germanium, or any other etchable material.

32. The method of claim 19 further wherein:

said microneedle is one of a plurality of microneedles used as a form to make a mold for production of microneedles from a moldable material.

33. A method of forming a plurality of hollow microneedles on a substrate with integrated, fluidic microchannels comprising:

patterning a first side of said substrate to define one or more microchannels;

patterning said first side to define first holes aligned to said microchannels;

etching said first holes into said substrate to a desired depth;

patterning said second side of said substrate to define second holes aligned to both the previously defined channel structures and to said first holes;

etching said second holes into said substrate until said second holes operatively connected with said first holes;

defining columns on said second side of said substrate roughly surrounding said second holes by removing portions of said substrate to a desired depth with a center of said columns at a desired position relative to said second holes;

isotropically etching said columns to form a vertical axial surface around said second holes, said vertical axial surface having a rounded cross-sectional profile between an external end of said second hole and a base at said substrate.

34. The method of claim 33 further comprising:

patterning said first holes to be approximately 30 micrometer across;

wherein said first holes are etched to a depth between about 20% to 80% of the thickness of said substrate;

patterning said second holes to be approximately 10 micrometer across;

wherein said second holes are etched to a depth between about 20% to 80% of the thickness of said substrate.

35. The method of claim 33 further comprising:

using forming said columns in order to achieve desired shank heights while columns are attached to a supporting substrate.

36. The method of claim 33 further wherein:

said microchannels are successfully filled by capillary action with either non-biological fluids (e.g., glycerol, ethanol, surrogate interstitial fluid (ISF) and water) and/or biological fluids (e.g., ISF and whole blood) when an external openings in said second holes are placed in proximity to one or more of said fluids.

37. The method of claim 33 further wherein:

said microneedles are machined from single crystal silicon to a shank height of 250-350 microns with 300 microns center-to-center spacing; and

said microneedles'"'"' size, density and shape are controlled by independent processing steps.

38. A microneedle device with integrated channels comprising:

a chip formed of one or more substantially solid materials comprising at least two surfaces referred to as a microneedle side and an opposite side and further comprising a thickness;

a plurality of microneedles formed in said materials, with tips extending from said microneedle side wherein each microneedle comprises a needle shaft with a base;

off-center, needle boreholes in a portion of said microneedles, up to all of said microneedles; and

a reservoir for fluid connected to multiple of said portion of said microneedles on the opposite side of the wafer opposite the needle tips and operatively connected by one or more micro-channels;

39. The device of claim 38 wherein said system is able to draw fluid from the tip of the needle into the micro-channels by capillary action, while the needle tips reside inside the skin.

40. The device of claim 38 wherein:

said off-center, needle boreholes are arranged in a plurality of said needles so that the tips of said needles are substantially solid, and said holes open at a space on said shaft somewhat below said tips.

41. The device of claim 38 further wherein:

said first material is one or more materials selected from a group comprising polymorphous silicon, crystalline silicon, single-crystal silicon, gallium, plastic, germanium, minerals (e.g. quartz), other semiconducting materials (e.g. doped silicon, doped germanium, etc.), ceramics, and metals;

said second material is one or more materials selected from the group comprising glass, plastic, minerals (e.g. quartz), ceramics, and metals.

42. The device of claim 38 further wherein:

said chip has overall dimensions of about 2 cm long×

1 cm wide×

0.1 cm thick.

43. The device of claim 38 further wherein:

said plurality of microneedles comprises about 40-100 microneedles, wherein each microneedle comprises a 170-350 micrometer tall needle shaft with about a 120 micrometer base diameter, on about 300 micrometer centers.

44. The device of claim 38 further wherein:

a portion of said boreholes at near said second side extend to contact said second material to increase a solid-liquid interface area and decrease a contact angle thereby providing enough capillary force to draw fluid from an outlet of said micro-needles and into a backside channel where surface tension continues to draw fluid into said channel.