Method of manufacturing microneedle structures using soft lithography and photolithography

• US 6,663,820 B2
• Filed: 03/14/2001
• Issued: 12/16/2003
• Est. Priority Date: 03/14/2001
• Status: Expired due to Term

• Current Assignee: Corium, Inc.
• Original Assignee: The Procter & Gamble Company
• Inventors: Sherman, Faiz Feisal, Owens, Grover David, Arias, Francisco
• Primary Examiner(s): Vargot, Mathieu D.
• Application Number:
  US09/808,534
• Publication Number:
  US 20020133129A1
• Time in Patent Office: 1,007 Days
• Field of Search: 264/400, 264/482, 264/496, 264/219, 264/154, 264/322, 264/227, 264/225, 264/319, 205/70, 205/164, 216/11, 216/41
• US Class Current: 264/496
• CPC Class Codes: A61B 5/1411 by percutaneous method, e.g. by lancet
• 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 5/150419 comprising means for capillary action
• CPC Class Codes: A61B 5/150984 Microneedles or microblades
• 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
• CPC Class Codes: B81C 2201/034 Moulding

Abstract

A method for manufacturing microneedle structures is disclosed using soft lithography and photolithography, in which micromold structures made of a photoresist material or PDMS are created. The micromold manufacturing occurs quite quickly, using inexpensive materials and processes. Once the molds are available, using moldable materials such as polymers, microneedle arrays can be molded or embossed in relatively fast procedures. In some cases a sacrificial layer is provided between the forming micromold and its substrate layer, for ease of separation. The microneedles themselves can be solid projections, hollow “microtubes,” or shallow “microcups.” Electrodes can be formed on the microneedle arrays, including individual electrodes per hollow microtube.

Claims

1. A method for fabricating microneedles, said method comprising:

(a) providing a substrate that includes a plurality of microstructures;

(b) coating said substrate with a layer of a first moldable material that takes the negative form of said plurality of microstructures, and hardening said first moldable material;

(c) separating said hardened first moldable material from said substrate, thereby creating a micromold from said hardened first moldable material containing said plurality of microstructures; and

(d) applying a second moldable material onto said micromold, allowing said second moldable material to harden using a soft lithography procedure, then separating said hardened second moldable material from said micromold, thereby creating a microneedle structure from said hardened second moldable material having the three-dimensional negative form of said plurality of microstructures of the patterned micromold;

wherein said microneedle structure comprises one of;

(a) a plurality of solid protrusions, (b) a plurality of hollow protrusions forming through-holes, (c) a plurality of hollow protrusions forming microcups that do not extend entirely through said hardened second moldable material, or (d) a plurality of solid protrusions, each having at least one surface external channel.

2. The method as recited in claim 1, wherein said first moldable material comprises PDMS, said second moldable material comprises a prepolymer, and said substrate comprises one of silicon or a metallic substance;

and wherein said microneedle structure comprises a polymeric material.

3. The method as recited in claim 1, wherein said substrate is constructed by:

beginning with a wafer material, coating said wafer material with at least one layer of a photoresist material, and patterning said photoresist material with a plurality of microstructures by use of a photolithography procedure, such that said patterned photoresist material comprises said plurality of microstructures; and

wherein said first moldable material is processed and hardened by a second soft lithography procedure.

4. The method as recited in claim 3, wherein said wafer comprises silicon, said photoresist material comprises SU-8, said first moldable material comprises PDMS, and said second moldable material comprises a prepolymer;

and wherein said microneedle structure comprises a polymeric material.

5. A method for fabricating microneedles, said method comprising:

(a) providing a substrate that includes a plurality of microstructures;

(b) coating said substrate with a layer of a first moldable material that takes the negative form of said plurality of microstructures, and hardening said first moldable material;

(c) separating said hardened first moldable material from said substrate, thereby creating a micromold from said hardened first moldable material containing said plurality of microstructures;

(d) applying a second moldable material onto said micromold, allowing said second moldable material to harden using a soft lithography procedure, then separating said hardened second moldable material from said micromold, thereby creating a microneedle structure from said hardened second moldable material having the three-dimensional negative form of said plurality of microstructures of the patterned micromold;

(e) providing a second substrate that includes a second plurality of microstructures, wherein said second plurality of microstructures is substantially complementary in shape as compared to said first plurality of microstructures;

(f) coating said second substrate with a layer of a third moldable material that takes the negative form of said second plurality of microstructures, and hardening said third moldable material;

(g) separating said hardened third moldable material from said second substrate, thereby creating a second micromold from said hardened third moldable material containing said second plurality of microstructures;

(h) applying a fourth moldable material onto said second micromold, allowing said fourth moldable material to harden using a soft lithography procedure, then separating said hardened fourth moldable material from said second micromold, thereby creating a second microneedle structure from said hardened fourth moldable material having the three-dimensional negative form of said second plurality of microstructures of the patterned second micromold; and

(i) applying a layer of a fifth moldable material upon one of said first or second microneedle structures, placing said first and second microneedle structure into a face-to-face relationship to thereby sandwich said layer of fifth moldable material therebetween, allowing said layer of fifth moldable material to harden using a soft lithography procedure, then separating said hardened fifth moldable material from both said first and second microneedle structures, thereby creating a third microneedle structure from said hardened fifth moldable material having the three-dimensional negative form of both said first and second microneedle structures.

6. The method as recited in claim 5, wherein said first and third moldable materials comprise PDMS, said second and fourth moldable materials comprise a prepolymer, said substrate comprises one of silicon or a metallic substance, and said fifth moldable material comprises a prepolymer;

and wherein said first, second, and third microneedle structures each comprises a polymeric material.

7. A method for fabricating microneedles, said method comprising:

(a) providing a substrate that includes a plurality of microstructures;

(b) coating said substrate with a layer of a first moldable material that takes the negative form of said plurality of microstructures, and hardening said first moldable material;

(c) separating said hardened first moldable material from said substrate, thereby creating a micromold from said hardened first moldable material containing said plurality of microstructures; and

(d) applying a second moldable material onto said micromold, allowing said second moldable material to harden using a soft lithography procedure, then separating said hardened second moldable material from said micromold, thereby creating a microneedle structure from said hardened second moldable material having the three-dimensional negative form of said plurality of microstructures of the patterned micromold;

wherein said first moldable material after hardening exhibits a flexibility characteristic and, therefore, can be deformed to a predetermined extent without breaking; and

further comprising;

after creating said micromold from said hardened, flexible first moldable material, deforming said micromold during the step of applying the second moldable material onto said micromold, thereby creating either a concave or convex micromold.