WO2001036036A1

WO2001036036A1 - Methods of fabricating microneedle arrays using sacrificial molds, and microneedle arrays fabricated thereby

Info

Publication number: WO2001036036A1
Application number: PCT/CA2000/001210
Authority: WO
Inventors: Robert L. Wood; Henry A. Wynands; Karen W. Markus
Original assignee: Jds Uniphase Corporation
Priority date: 1999-11-18
Filing date: 2000-10-18
Publication date: 2001-05-25
Also published as: AU7895100A; US6511463B1; US7332197B2; US20030111759A1

Abstract

Microneedle arrays are fabricated by providing a sacrificial mold including a substrate and an array of posts, preferably solid posts, projecting therefrom. A first material is coated on the sacrificial mold including on the substrate and on the array of posts. The sacrificial mold is removed to provide an array of hollow tubes projecting from a base. The inner and outer surfaces of the array of hollow tubes are coated with a second material to create the array of microneedles projecting from the base. A third material is molded into the channels and on the face of the master mold, to create the sacrificial mold. The sacrificial mold then is separated from the master mold. Alternatively, wire bonding may be used to wire bond an array of wires to a substrate to create the sacrificial mold.

Description

METHODS OF FABRICATING MICRONEEDLE ARRAYS USING SACRIFICIAL MOLDS, AND MICRONEEDLE ARRAYS FABRICATED

THEREBY

Field of the Invention

This invention relates to hypodermic needles, and more particularly to microneedles and fabπcation methods thereof

Background of the Invention Hypodermic needles are widely used in the biomedical field for injection into and extraction from living tissue Hypodermic needles generally have a relatively large diameter, for example on the order of millimeters Unfortunately, the large diameter can damage biological tissue duπng penetration Moreover, tissue penetration often is painful due to the relatively large needle diameter Accordingly, microneedles are being developed, that can have diameters that are on the order of microns The smaller diameter needle can reduce damage to living tissue and/or reduce pain More precise injection and extraction also may be provided In order to inject or extract a requisite amount of liquid through a microneedle of relatively small diameter, an array of microneedles, often referred to as a microneedle array, generally is provided For example, a microneedle array may have dimensions on the order of 1 cm² and may include tens, hundreds or even thousands of microneedles thereon Microneedles are descπbed in U S Patent 5,457.041 to Gmaven et al entitled Needle Arra\ and Method of Introducing Biological Substances Into Living Cells Using the Needle Array, U S Patent 5.658,515 to Lee et al entitled Polymer Micromold and Fabrication Process, U S Patent 5,591,139 to Lm et al entitled IC-Processed Microneedles, and U S Patent 5.928.207 to Pisano et al entitled Microneedle With Isotropically Etched Tip and Method of Fabricating Such a Device

Microneedles may be fabπcated using micromachming or other processes that are used to form microelectromechanical systems (MEMS) These fabπcation steps may be similar to those that are used for fabπcating integrated circuit microelectronic devices and thereby may be capable of relatively low-cost fabπcation in large numbers Unfortunately, notwithstanding the applicability of microelectronic fabπcation techniques to the fabπcation of microneedle arrays, there continues to be a need to provide improved fabπcation processes for microneedle arrays that can produce microneedle arrays at very low cost, for example, less than one dollar per microneedle array and preferably less than one cent per microneedle array

Summary of the Invention

The present invention provides methods of fabricating microneedle arrays by providing a sacπficial mold including a substrate and an array of posts, preferably solid posts, projecting therefrom. A first mateπal is coated on the sacπficial mold including on the substrate and on the array of posts. The sacrificial mold is removed to provide an aπay of hollow tubes projecting from a base The outer surfaces, and preferably the inner surfaces, of the array of hollow tubes are coated with a second mateπal to create the array of microneedles projecting from the base. By using a sacπficial molding technique, low cost fabrication of microneedles may be obtained. Moreover, the sacπficial mold may be fabπcated from plastic and/or metal, and need not be fabπcated from a relatively expensive silicon semiconductor wafer. Low cost microneedle arrays thereby may be provided.

The sacπficial mold may be fabπcated by fabπcating a master mold, including an array of channels that extend into the master mold from a face thereof. A third material is molded into the channels and on the face of the master mold, to create the sacrificial mold. The sacπficial mold then is separated from the master mold. Alternatively, wire bonding that is widely used in the fabπcation of microelectronic devices, may be used to wire bond an aπay of wires to a substrate to create the sacrificial mold

The first mateπal preferably is coated on the sacπficial mold by plating When the sacrificial mold is not conductive, a plating base preferably is formed on the sacπficial mold including on the substrate and on the array of posts pπor to plating. The inner and outer surfaces of the array of hollow tubes preferably are coated with a second mateπal by overplating the second mateπal on the inner and outer surfaces of the array of hollow tubes The plating base preferably compπses at least one of copper and gold. including alloys thereof The first mateπal preferably compπses at least one of nickel and chromium, including alloys thereof. The second mateπal preferably compπses at least one of gold, rhodium, platinum and ruthenium, including alloys thereof. When coating the first material on the sacrificial mold including on the substrate and on the array of posts, the tips of the array of posts preferably are left uncoated so that open tubes later result. Alternatively, the tips may be removed to provide the array of hollow tubes. Moreover, the tips of the array of hollow tubes may be sharpened, for example by etching the tips. The first material may be coated on the array of posts including an obliquely extending portion of the tips. Thus, an obliquely angled tip may be formed which can increase the ability to penetrate living tissue without clogging.

First and second preferred embodiments for fabricating microneedle arrays according to the present invention now will be described. The first embodiment uses a soluble mold, whereas the second embodiment uses an array of wires projecting from a substrate.

In particular, according to the first prefeπed embodiments, a soluble mold is provided including a substrate and an array of posts, preferably solid posts, projecting therefrom. A plating base is formed on the soluble mold including on the substrate and on the array of posts. A plated first material is formed on the plating base except for across the tips of the array of posts. The soluble mold then is at least partially dissolved and thereby removed, to provide an array of hollow tubes projecting from a base. In order to provide the array of hollow tubes, the tips of the tubes may be removed in a separate operation. The plating base preferably also is at least partially dissolved and removed along with the soluble mold. The inner and outer surfaces of the array of hollow tubes preferably are overplated with a second material, to create the array of microneedles projecting from the base. The tips of the array of hollow tubes may be sharpened, preferably by etching the tips. The soluble mold preferably is fabricated by fabricating the master mold including an array of channels that extend into the master mold from a face thereof. A soluble material then is molded into the channels and on the face of the master mold, to create the soluble mold. Conventional molding processes, such as injection molding, embossing, casting and/or sheet forming may be used. The soluble mold then is separated from the master mold. When plating and/or overplating the microneedle array, the tips of the array preferably are masked to prevent plating of the tips across the entrance of the tube. Masking may be accomplished by masking the tips of the soluble mold to prevent formation of the plating base on the tips Alternatively, the tips of the plating base may be masked to prevent further plating thereon When masking, the tips preferably are masked at an oblique angle to thereby allow plating of an obliquely extending portion of the tips, and thereby create angled needle points that can have reduced susceptibility to clogging

In second preferred embodiments of the invention, a sacπficial mold is provided including a substrate and an array of wires projecting therefrom A plated first mateπal is formed on the sacπficial mold including on the substrate and on the array of wires except for across the tips of the wires The sacπficial mold is removed to provide an array of hollow tubes projecting from a base In order to provide the array of hollow tubes, the tips of the tubes may be removed m a separate operation The inner and outer surfaces of the array of hollow tubes are overplated with a second mateπal, to create the array of microneedles projecting from the base In a preferred embodiment, the steps of wire bonding, plating, removing and overplating are performed in a continuous process followed by smgulating individual arrays of microneedles

The sacπficial mold preferably is provided by wire bonding an array of wires to a substrate to create the sacπficial mold. Wire bonding may be performed by wire bonding both ends of a plurality of wires to the substrate, to create a plurality of loops of wires on the substrate. The loops of wires then may be cut, or the centers of the loops may be masked to prevent plating, to create the sacπficial mold Shaφening and oblique angle tip masking also preferably are performed, as was descπbed above

Microneedle arrays according to the present invention preferably compπse a monolithic core including a substrate having an array of holes therein and an array of hollow tubes that project from the substrate, a respective one of which surrounds a respective one of the array of holes An overlayer also is provided on the monolithic core, on the outer surfaces of the array of hollow tubes, on the tips of the array of hollow tubes, and preferably on the inner surfaces of the array of hollow tubes

The monolithic core also may compπse an array of shoulders that surround the array of hollow tubes adjacent the substrate The shoulders may aπse from the wire bonding region between the wires and the substrate of the sacπficial mold The array of hollow tubes also may have scalloped outer surfaces The scalloped outer surfaces may be caused by deep reactive ion etching which may be used to form the master mold The array of hollow tubes preferably includes sharp ends that more preferably extend at an oblique angle relative to the substrate The monolithic core preferably compπses at least one of nickel and chromium including alloys thereof, most preferably nickel including alloys thereof The overlayer preferably compπses at least one of gold, rhodium, platinum and ruthenium, and alloys thereof, and most preferably gold or alloys thereof Microneedle arrays may be provided thereby

Brief Description of the Drawings

Figures 1A-1F are cross-sectional views of microneedle arrays duπng intermediate fabπcation steps, according to the present invention

Figures 1A', 1C and 1D'-1D'" are enlarged cross-sectional views showing alternate fabπcation steps for Figures 1A, 1C and ID respectively

Figures 2A-2E are cross-sectional views of other microneedle arrays duπng intermediate fabπcation steps according to the present invention.

Detailed Description of Preferred Embodiments

The present invention now will be descπbed more fully hereinafter with reference to the accompanying drawings, in which preferred embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. In the drawings, the thickness of layers and regions are exaggerated for claπty Like numbers refer to like elements throughout It will be understood that when an element such as a layer, region or substrate is referred to as being "on" another element, it can be directly on the other element or intervening elements may also be present. In contrast, when an element is referred to as being "directly on" another element, there are no intervening elements present.

Referπng now to Figure 1A, a master mold 102 is fabπcated. The master mold may compπse silicon, metal and/or other mold mateπals. The master mold 102 includes an array of channels 104 therein that extend into the master mold from a first face 102a thereof As shown m Figure 1A, the channels also may extend through the master mold 102 to a second face 102b thereof However, the channels need not extend entirely through the master mold The master mold may be between about 50μm and about 1mm in thickness, and the channels may be between about lOμm and about lOOμm m diameter The channels may be formed in the master mold using deep Reactive Ion Etching (RIE) m a silicon or other master mold and/or using the LIGA process in a metal mold, preferably nickel Deep RIE and the LIGA process are well known to those having skill in the art. and are descπbed, for example, in the assignee s web site www memsrus com It will be understood by those having skill m the art that although only nine channels 104 are illustrated in Figure 1A, fewer or more channels may be provided depending upon the desired number of microneedles In fact, only a single channel may be included in the array 104 A conventional microneedle array may have dimensions on the order of 1 cm^", similar to a conventional integrated circuit chip, and may contain tens, hundreds or thousands of needles However, a single needle also may be provided The needles may be equally spaced or unequally spaced It also will be understood that a single master mold may be used to fabπcate a plurality of microneedle arrays which then are diced into mdividual microneedle arrays after processing Thus, the master mold 102 may have an area on the order of 1 cm but may be 1000 cm or larger in area When forming the channels using deep RIE, the channels may have scalloped walls, as shown m the enlarged view of Figure 1A' These scalloped walls may replicate duπng subsequent steps, as will be descπbed below When LIGA or other processes are used to form the channels, smooth channels as shown in Figure 1A may be present, and may replicate duπng subsequent steps Referπng now to Figure IB, a soluble mateπal, such as a soluble polymer, including Poly Methyl Methacrylate (PMMA) or poly-carbonate, is molded into the channels 104 and on the face 102a of the master mold 102 to create a soluble mold 106 As shown in Figure IB, the soluble mold includes a substrate 108 and an array of posts 112, preferably solid posts, projecting therefrom The soluble mold may be created using conventional micromjection molding Since the soluble mold will be at least partially dissolved later m the process, as descπbed below, a material that can be at least partially dissolvable preferably is used It will be understood that conventional molding techniques may be used, including injection molding, embossing, casting and/or sheet forming.

Then, referring to Figure 1C, a plating base 114 is formed on the soluble mold including on the substrate 108 and on the array of posts 112. The plating base 114 may be formed by conventional sputtering or other conventional techniques. The plating base may comprise copper, gold and/or alloys thereof, more preferably copper and/or alloys thereof. The thickness of the plating base may be about 1000A.

Still referring to Figure 1C, it can be seen that the plating base covers the array of solid posts 112 including across the tips 112a thereof. Since it is desirable to eventually form hollow microneedles with open tips, the plating base may be prevented from depositing on the tips 112a of the posts 112 by masking the tips 112a. Alternatively, after deposition of the plating base, the tips 112a may be dipped into an etchant to remove the plating base 114 from on the tips 112a, as shown in Figure 1C. In yet another alternative that will be described in connection with Figure ID, the plating base 114 is allowed to remain across the tips 112a of the solid posts 112, but a subsequent plated layer is masked from the tips or is subsequendy removed.

Referring now to Figure ID, a plated first material 116 is formed on the plating base. The first material preferably comprises nickel, chromium and/or alloys thereof, more preferably nickel and/or alloys thereof, and may have a thickness between about lOμm and about 20μm. Multiple sublayers of first materials also may be formed.

As shown in Figure ID, prior to plating the first material 116, a mask 118 may be formed on the tips 112a to prevent plating across the tips 112a. In another alternative, the first material 116 may be plated across the tips 112a and then the first material and optionally the plating base across the tips 112a may be removed, for example by dipping into a chemical etch. The ends of the posts 112 also may be removed. In yet another alternative, the first material 116, and optionally the plating base across the tips 112a may be removed using mechanical abrasion or other known techniques. In order to ensure that the posts 112 do not break during mechanical abrasion, the structure may first be encapsulated, for example in a spun-on polymer, the tips may be abraded and the spun-on polymer may be removed. In any of these alternative operations, the height of the hollow tubes also may be reduced as desired. Accordingly, the step of forming a plated first material on the plating base except for across the tips of the array of posts, according to the present invention, contemplates masking the tips so that the first mateπal is not plated on the tips or plating the first mateπal on the tips and then removing this mateπal. using any of the above-disclosed or other techniques

Referπng now to Figure IE. the mask 118 may be removed, if present, and the tips 116a of the first mateπal 116 may be sharpened, for example using mechanical and or chemical etching Shaφening may improve the punctuπng ability of the microneedle array Then, the soluble mold 106 is released, preferably by at least partially dissolving the soluble mold For example, when the soluble mold compπses PMMA, it may be dissolved in acetone The plating base 114 also preferably is dissolved to provide an array of hollow tubes 122 projecting from a base 124

Then, referπng to Figure IF. the outer surfaces, and preferably the inner surfaces, of the aπay of hollow tubes 122 are oveφlated with a second mateπal 132, to create an array of microneedles 134 projecting from a base 136 As shown in Figure IF, the base of the first layer 124 also preferably is oveφlated with the second mateπal. Both faces of the base also may be oveφlated. The second mateπal preferably compπses a biocompatible mateπal such as gold, rhodium, platinum, ruthenium and/or alloys thereof, and preferably gold. The thickness of the second mateπal preferably is between about 0.5μm and about lOμm. Multiple sublayers of the second mateπals also may be formed. Since the inside and outside surfaces of the microneedles 134 are oveφlated, a biocompatible microneedle may be provided.

Figures 1D'-1D'" are enlarged views of the indicated portion of the Figure ID, and illustrate another aspect of the present invention As is well known to those having skill in the art, it is desirable for a needle to have a slanted or oblique tip to allow improved penetration and reduced clogging In order to form a slanted or oblique tip. the mask 118 may be formed asymmetπcally on the tips 112a. For example, as shown in Figure ID, the mask 118 may be a photoresist The photoresist is baked to dry the photoresist. The photoresist then is exposed to radiation 138 at an oblique angle The photoresist then is developed to produce the asymmetπcal mask 118'. Plating of the first mateπal 116 then is performed to form a layer of the first material 116' on the plating base 114 that is asymmetπcal and provides a slanted tip In other alternatives, the masking mateπal may be deposited at an oblique angle or other techniques may be used to asymmetπcally form the mask on the tips The asymmetπcal mask may be formed directly on the plating base or the first material. In yet another alternative, asymmetrical etching techniques may be used to asymmetπcally etch the tips to provide slanted tips.

Referπng again to Figure IF, a microneedle array 140 according to the present invention includes a monolithic core 136 including a substrate 136a having an array of holes 136b therein, and an array of hollow tubes 136c that project from the substrate 136a, a respective one of which surrounds a respective one of the array of holes 136b. An overlayer 132 also is provided, that extends on the substrate 136a, on the outer surfaces of the array of hollow tubes 136c. on the tips 136d of the hollow tubes and preferably on the inner surfaces of the array of hollow tubes 136c The overlayer also may extend on the back face of the substrate 136a The hollow tubes may have scalloped outer surfaces reflecting the scallops shown in Figure 1A'. due to the scalloped surfaces of the channels 104 The hollow tubes preferably include shaφ ends as shown in Figure IF, and the ends of the arrays of hollow tubes preferably extend at an oblique angle relative to the substrate as shown in Figure ID" The monolithic core preferably comprises at least one of nickel and chromium, includmg alloys thereof, and the overlayer preferably compπses at least one of gold, rhodium, platinum and ruthenium and alloys thereof. More preferably, the monolithic core compπses nickel or alloys thereof and the overlayer more preferably compπses gold or alloys thereof. The monolithic core and/or the overlayer may compπse multiple sublayers Figures 2A-2E are cross-sectional views of microneedle arrays duπng intermediate fabπcation steps, according to the present invention. In general, Figures 2A-2E wire bond an array of wires to a substrate to create a sacπficial mold, rather than molding from a master mold, as was the case in Figures 1A-1B The other processing steps may be similar to Figures 1C-1F, as will be descπbed below Moreover, the optional steps of Figures lC'-lD" also may be applied, as will be descπbed below

More specifically, referπng to Figure 2A, a sacπficial mold 206 is fabπcated by wire bonding a plurality of wires 212 to a substrate 208. Wire bonding is a technique that is well known to those having skill in the microelectronic fabrication art, and is descπbed, for example, in U.S. Patents 5.476.211 to Khandros entitled Method of Manufacturing Electrical Contacts, Using a Sacrificial Member. 5,852.871 to Khandros entitled Method of Making Raised Contacts on Electronic Components; and 5.884,398 to Eldπdge et al. entitled Mounting Spring Elements on Semiconductor Devices. The substrate 208 may be a discrete substrate that is large enough for one or more microneedle arrays. Alternatively, and preferably, the substrate 208 is a continuous substrate and wires 212 are wire-bonded to the substrate 208 in a continuous wire bonding process. As shown in Figure 2A. both ends of a plurality of wires 212 are bonded to the substrate 208 to create a plurality of loops of wires on the substrate 208. Then, as shown m Figure 2A. the wires may be cut, for example along a line 210 that extends parallel to the substrate 208. to provide an array of wires 212' that project from the substrate 208 Alternatively, one end of a plurality of wires may be wire-bonded to the substrate 208 to produce the structure of Figure 2B, without first forming the loops of Figure 2A and then cutting along the line 210 As shown in Figure 2B. each wire 212' includes a tip 212a and a shoulder 212b that is characteπstic of wire bonding. The substrate 208 preferably compπses copper or alloys thereof and the wires 212' also preferably compπse copper or alloys thereof. Referπng now to Figure 2C, a plated first mateπal 216 is formed on the sacπficial mold 206 including on the substrate and on the array of wires 212', except for across the tips 212a of the wires 212'. The first material may be similar to the first mateπal 116 of Figures 1A. As was already descπbed m connection with Figures 1A-1F, many alternatives may be provided so as not to block the tips 212a of the wires 212'. In one example, shown in Figure 2C, a mask 218 is formed on the tips 212a. The mask may be formed m the same manner as mask 118 of Figure ID, and may be asymmetπcally formed as was shown m Figures 1D'-1D'".

Then, referπng to Figure 2D, the sacπficial mold 206 is removed to provide an array of hollow tubes 222 projecting from a base 224 The tips of the tubes may be shaφened. as was descπbed in connection with Figure IE The tips may be removed to open the hollow tubes as was described above

Then, referπng to Figure 2E, the outer surfaces, and preferably the inner surfaces, of the array of hollow tubes 222, and preferably the base 224, and optionally the back face of the base 224 are oveφlated with a second mateπal 232, to create the array of microneedles projecting from the base 224 The second mateπal may compπse the same mateπals as the second mateπal 132 of Figure IF The microneedle arrays then may be singulated from the continuous structure of Figure 2E The fabπcation methods of Figures 2A-2E can eliminate the need to perform micromoldmg and can utilize well known wire bonding techniques However, since the wires generally are bonded individually rather than molded as a unit, this fabπcation process may be more costh Microneedle arrays 240 that are fabπcated according to methods of Figures 2A-2E include a monolithic core 236 including the substrate 236a having an aπay of holes 236b therein and an array of hollow tubes 236c that project from the substrate 236, a respective one of which surrounds a respective one of the aπay of holes 236b An overlayer 232 is provided on the monolithic substrate core 236, on the outer surfaces of the aπay of hollow tubes 236c. on the tips 236d of the aπay of hollow tubes and preferably on the inner surfaces of the array of hollow tubes Due to the wire bonding process, an array of shoulders 242 also is provided that surrounds the aπay of hollow tubes 236c adjacent the substrate 236 As was already descπbed. the aπay of hollow tubes may include shaφ ends and/or may extend at an oblique angle relative to the substrate. Accordingly, microneedle arrays need not use silicon semiconductor substrates and/or silicon micromachmmg techniques, both of which may be costly and/or complex Rather, they can use metal and/or plastic substrates, as was descπbed above Accordingly, low cost microneedle arrays and/or simplified fabπcation methods therefor may be provided. In the drawings and specification, there have been disclosed typical preferred embodiments of the invention and, although specific terms are employed, they are used in a generic and descπptive sense only and not for puφoses of limitation, the scope of the invention being set forth in the following claims

Claims

What is claimed is:

1 A method of fabπcating a microneedle aπay compnsmg the steps of providing a sacrificial mold including a substrate and an aπay of posts projecting therefrom coating a tirst material on the sacrificial mold including on the substrate and on the aπay of posts removing the sacπficial mold to provide an aπay of hollow tubes projecting from a base, and coating the outer surfaces of the aπay of hollow tubes with a second mateπal to create the aπav of microneedles projecting from the base

2 A method according to Claim 1 wherein the step of providing a sacrificial mold compπses the steps of fabπcating a master mold including an array of channels that extend into the master mold from a face thereof, molding a third mateπal into the channels and on the face of the master mold to create the sacπficial mold, and separating the sacπficial mold from the master mold

3 A method according to Claim 1 wherein the step of providing a sacπficial mold compπses the step of wire bonding an array of wires to a substrate to create the sacπficial mold

4 A method according to Claim 1 wherein the step of coating a first material compπses the step of plating the first mateπal on the sacπficial mold including on the substrate and on the aπay of solid posts

5 A method according to Claim 4 wherein the step of plating is preceded by the step of forming a plating base on the sacrificial mold including on the substrate and on the aπay of posts, and wherein the step of plating comprises the step of plating the first mateπal on the plating base

6 A method according to Claim 1 wherein the step of removing compπses the step of dissolving the sacrificial mold

7 A method according to Claim 1 wherein the step of coating the outer surfaces comprises the step of oveφlating the second material on the outer surfaces of the aπay of hollow tubes

8 A method according to Claim 1 wherein the step of coating a first mateπal comprises the step of coating the first mateπal on the sacrificial mold including on the substrate and on the aπay of posts, except for across the tips of the aπay of posts

9 A method according to Claim 1 further compπsmg the step of shaφenmg the tips of the aπay of hollow tubes

10. A method according to Claim 1 wherein the step of coating a first mateπal compπses the step of coating the first mateπal on the sacπficial mold including on the substrate and on the array of posts, including an obliquely extending portion of the tips of the array of posts.

11 A method according to Claim 1 wherein the step of removing compπses the steps of removing the sacπficial mold from the first material, and removing the tips of the first material to provide the aπay of hollow tubes projecting from the base

1 A method according to Claim 1, wherein the step of coating comprises the step of coating the inner and outer surfaces of the aπay of hollow tubes with the second mateπal to create the array of microneedles projecting from the base

13. A method according to Claim 12 wherein the step of coating the inner and outer surfaces compπses the step of oveφlating the second material on the inner and outer surfaces of the aπay of hollow tubes.

14 A method of fabricating a microneedle array comprising the steps of: providing a soluble mold including a substrate and an aπay of posts projecting therefrom; forming a plating base on the soluble mold including on the substrate and on the aπay of posts; forming a plated first material on the plating base except for across the tips of the aπay of posts: at least partially dissolving the soluble mold to provide an array of hollow tubes projecting from a base; and oveφlating the outer surfaces of the array of hollow tubes with a second material to create the array of microneedles projecting from the base.

15. A method according to Claim 14 wherein the step of providing a soluble mold compπses the steps of: fabπcating a master mold including an array of channels that extend into the master mold from a face thereof; molding a soluble mateπal into the channels and on the face of the master mold to create the soluble mold; and separating the soluble mold from the master mold.

16. A method according to Claim 14 further compπsmg the step of: shaφening the tips of the aπay of hollow tubes

17 A method according to Claim 16 wherein the step of shaφening compπses the step of etching the tips of the aπay of hollow rubes

18. A method according to Claim 14 wherein the at least partially dissolving step comprises the step of at least partially dissolving the soluble mold and the plating base to provide an array of hollow tubes projecting from a base.

19. A method according to Claim 14 wherein the step of forming a plated first material is preceded by the step of masking the tips of the aπay of posts to prevent plating of the tips.

20. A method according to Claim 14 wherein the step of forming a plating base is preceded by the step of masking the tips of the soluble mold to prevent formation of the plating base on the tips.

21. A method according to Claim 19 wherein the step of masking the tips comprises the step of masking the tips of the array of posts at an oblique angle thereto to prevent plating of an obliquely extending portion of the tips.

22. A method according to Claim 20 wherein the step of masking the tips comprises the step of masking the tips of the soluble mold at an oblique angle thereto to prevent formation of the plating base on an obliquely extending portion of the tips.

23. A method according to Claim 20 wherein the plating base comprises at least one of copper and gold, wherein the first material comprises at least one of nickel and chromium and wherein the second material comprises at least one of gold, rhodium, platinum and ruthenium.

24. A method according to Claim 14 wherein the following step is performed between the steps of at least partially dissolving and oveφlating: removing the tips of the hollow tubes to reduce the height of the hollow tubes.

25. A method according to Claim 14 wherein the step of oveφlating comprises the step of: oveφlating the inner and outer surfaces of the array of hollow tubes with the second material to create the array of microneedles projecting from the base.

26. A method of fabricating a microneedle aπay comprising the steps of: providing a sacrificial mold including a substrate and an aπay of wires projecting therefrom; forming a plated first mateπal on the sacrificial mold including on the substrate and on the array of wires except for across the tips of the wires: removing the sacrificial mold to provide an aπay of hollow tubes projecting from a base; and oveφlating the outer surfaces of the aπay of hollow tubes with a second material to create the array of microneedles projecting from the base.

27. A method according to Claim 26 wherein the step of providing a sacrificial mold comprises the step of wire bonding an array of wires to a substrate to create the sacrificial mold.

28. A method according to Claim 27 wherein the steps of wire bonding, plating, removing and oveφlating are performed in a continuous process and wherein the step of oveφlating is followed by the step of singulating individual arrays of microneedles.

29. A method according to Claim 27 wherein the step of wire bonding compπses the steps of: wire bonding both ends of a plurality of wires to the substrate to create a plurality of loops of wires on the substrate; and cutting the loops of wires to create the sacrificial mold.

30. A method according to Claim 26 further comprising the step of: shaφening the tips of the aπay of hollow tubes.

31. A method according to Claim 30 wherein the step of shaφening compπses the step of etching the tips of the aπay of hollow mbes.

32. A method according to Claim 26 wherein the step of forming a plated first mateπal is preceded by the step of masking the tips of the aπay of wires to prevent plating of the tips

33 A method according to Claim 32 wherein the step of masking the tips compπses the step of masking the tips of the aπay of wires at an oblique angle to prevent plating of an obliquely extending portion of the tips

34 A method according to Claim 26 wherein the wires compπse at least one of copper and gold, wherein the first mateπal comprises at least one of nickel and chromium and wherein the second mateπal compπses at least one of gold, rhodium, platinum and ruthenium.

35. A method according to Claim 26, wherein the following step is performed between the steps of removing and oveφlating: removing the tips of the hollow tubes to reduce the height of the hollow mbes.

36 A method according to Claim 26 wherein the step of oveφlating comprises the step of: oveφlating the inner and outer surface of the array of hollow tubes with the second mateπal to create the aπay of microneedles projecting from the base

37 A microneedle aπay comprising a monolithic core including a substrate having an array of holes therein and an array of hollow mbes that project from the substrate, a respective one of which suπounds a respective one of the aπay of holes; and an overlayer that extends on the substrate, on the outer surfaces of the array of hollow tubes and on the tips of the aπay of hollow tubes

38 A microneedle array according to Claim 37 wherein the monolithic core further compπses an aπay of shoulders that suπound the array of hollow tubes adjacent the substrate, and wherein the overlayer also extends on the aπay of shoulders

39 A microneedle aπay according to Claim 37 wherein the array of hollow tubes compπses an aπay of hollow mbes having scalloped outer surfaces

40 λ microneedle aπay according to Claim 37 wherein the array of hollow tubes includes shaφ tips

41 A microneedle aπay according to Claim 37 wherein the tips of the aπays of hollow mbes extend at an oblique angle relative to the substrate

42 A microneedle array according to Claim 40 wherein the shaφ tips of the aπays of hollow mbes extend at an oblique angle relative to the substrate.

43 A microneedle array according to Claim 37 wherein the monolithic core compπses at least one of nickel and chromium and wherein the overlayer compπses at least one of gold, rhodium, platinum and ruthenium.

44 A microneedle array according to Claim 37 wherein the monolithic core compπses nickel and wherein the overlayer compπses gold

45 A microneedle aπay according to Claim 37 wherein the overlayer also extends on the inner surfaces of the array of hollow mbes

46 A method of fabricating a microneedle aπay compπsing the steps of fabπcating a monolithic core including a substrate having an array of holes therein and an aπay of hollow tubes that project from the substrate, a respective one of which suπounds a respective one of the aπay of holes, and forming an overlayer that extends on the substrate, on the outer surfaces of the array of hollow tubes and on the tips of the aπay of hollow tubes

47. A method according to Claim 46 wherein the monolithic core further compπses an array of shoulders that suπound the aπay of hollow tubes adjacent the substrate, and wherein the overlayer also extends on the aπay of shoulders

48. A method according to Claim 46 wherein the aπay of hollow tubes compπses an aπay of hollow mbes having scalloped outer surfaces.

49. A method according to Claim 46 wherein the aπay of hollow mbes includes shaφ tips.

50. A method according to Claim 46 wherein the tips of the aπays of hollow tubes extend at an oblique angle relative to the substrate.

51. A method according to Claim 49 wherein the shaφ tips of the arrays of hollow tobes extend at an oblique angle relative to the substrate.

52. A method according to Claim 46 wherein the monolithic core comprises at least one of nickel and chromium and wherein the overlayer comprises at least one of gold, rhodium, platinum and ruthenium.

53. A method according to Claim 46 wherein the monolithic core compπses nickel and wherein the overlayer compπses gold.

54. A method according to Claim 46 wherein the overlayer also extends on the inner surfaces of the aπay of hollow mbes.