Tissue conforming microneedle device for drug delivery or biological fluid collection

Abstract

Microneedle arrays are provided for use on a contoured or flexible tissue surface. In one embodiment, the microneedle array includes a plurality of microneedles, each having a base portion, a tip end portion distal to the base portion, and body portion therebetween; and a flexible substrate which comprises a plurality of apertures, each of which are defined by (i) a plurality of substrate elements which are integral with the base portions of the microneedles, and (ii) at least one spring element connecting at least two of the substrate elements. The spring element may include a curved element, such as a C-shaped, U-shaped, or S-shaped element. Apertures may be defined, for example, by two substrate elements, which connected to three or four spring elements. A skin patch is provided for therapeutic or diagnostic applications, which includes the microneedle array and an adhesive material.

1 . A device for administration of a drug to a contoured or flexible tissue surface, the device comprising:
 a microneedle array which comprises
 a plurality of microneedles, each microneedle having a base portion, a tip end portion distal to the base portion, and body portion between the base portion and the tip end portion, and 
 an elastically stretchable substrate which comprises a plurality of apertures, each of which are defined by both (i) a plurality of substrate elements which are integral with the base portions of the microneedles, and (ii) at least one spring element integral with and connecting at least two of the substrate elements; and 
   at least one drug storage element, which contains a drug formulation, disposed adjacent to the microneedle array.   
     
     
         2 . The device of  claim 1 , wherein the drug storage element is attached to a first surface of the substrate, the first surface being opposed to a second surface of the substrate of the microneedle array, wherein the microneedles project from said second surface. 
     
     
         3 . The device of  claim 1 , wherein the drug storage element is coated onto an outer surface of the microneedles. 
     
     
         4 . The device of  claim 1 , wherein the drug storage element can flex and deform with substrate of the microneedle array. 
     
     
         5 . The device of  claim 1 , further comprising a release mechanism for releasing the drug formulation from the drug storage element to permit the drug formulation to pass through the apertures of the substrate of the microneedle array. 
     
     
         6 . The device of  claim 1 , wherein the drug storage element comprises a porous material, wherein the drug formulation is stored in pores of the porous material. 
     
     
         7 . The device of  claim 1 , further comprising an adhesive surface suitable for securing the device to the skin of a patient during administration of the drug formulation to the patient. 
     
     
         8 . The device of  claim 1 , further comprising a removable release liner, which covers the microneedles and apertures prior to use of the device. 
     
     
         9 . The device of  claim 1 , wherein at least one of the spring elements of the substrate comprises a curved element. 
     
     
         10 . The device of  claim 9 , wherein the curved element is C-shaped, U-shaped, or S-shaped. 
     
     
         11 . The device of  claim 1 , wherein at least one of the apertures of the substrate is defined by two substrate elements. 
     
     
         12 . The device of  claim 1 , wherein at least one of the substrate elements is connected to three or four spring elements. 
     
     
         13 . The device of  claim 1 , wherein at least one of the plurality of microneedles has a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion and in fluid communication with at least one of the apertures in the substrate. 
     
     
         14 . The device of  claim 13 , wherein the base portion of the at least one of the microneedles is untapered and has a substantially rectangular cross-sectional shape in a plane parallel to the substrate. 
     
     
         15 . The device of  claim 14 , wherein the at least one channel is open to two opposing surfaces of the microneedle. 
     
     
         16 . The device of  claim 13 , wherein the tip end portion of the at least one of the microneedles is tapered. 
     
     
         17 . The device of  claim 16 , wherein the at least one channel extends into the tapered tip end portion. 
     
     
         18 . The device of  claim 1 , wherein the elastically stretchable substrate and the microneedles are both formed of a biocompatible metal or polymer. 
     
     
         19 . The device of  claim 1 , wherein the microneedles have a length between 100 μm and 500 μm. 
     
     
         20 . A device for transdermal sampling of a biological fluid, the device comprising:
 comprising:
 a microneedle array which comprises
 a plurality of microneedles, each microneedle having a base portion, a tip end portion distal to the base portion, and body portion between the base portion and the tip end portion, and 
 
 an elastically stretchable substrate which comprises a plurality of apertures, each of which are defined by both (i) a plurality of substrate elements which are integral with the base portions of the microneedles, and (ii) at least one spring element integral with and connecting at least two of the substrate elements; and 
 at least one collection reservoir for retaining a biological fluid sample drawn through the microneedle array. 
   
     
     
         21 . The device of  claim 20 , further comprising a sensor for testing the biological fluid retained in the collection reservoir. 
     
     
         22 . A method for manufacturing a microneedle array comprising:
 (a) forming an elastically stretchable substrate which comprises a plurality of apertures, each of which are defined by (i) a plurality of substrate elements, and (ii) at least one spring element connecting at least two of the substrate elements; and   (b) forming a plurality of microneedles, each having a base portion, a tip end portion distal to the base portion, and body portion therebetween, wherein the base portions of the microneedles are integral with the substrate elements.   
     
     
         23 . The method of  claim 22 , which comprises forming in a planar substrate material the plurality of apertures, the plurality of substrate elements, and the plurality of spring elements, by removing selected portions of the substrate material. 
     
     
         24 . The method of  claim 23 , wherein the removal process comprises embossing, injection molding, casting, photochemical etching, electrochemical machining, electrical discharge machining, precision stamping, high-speed computer numerically controlled milling, Swiss screw machining, soft lithography, directional chemically assisted ion etching, laser cutting, or a combination thereof. 
     
     
         25 . The method of  claim 22 , wherein at least one of the plurality of microneedles has a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion and in fluid communication with at least one of the apertures in the substrate. 
     
     
         26 . A method of administering a drug to a patient in need thereof, comprising:
 inserting the microneedles of the device of  claim 1  into the skin of the patient to form holes in the stratum corneum; and   causing a fluid drug formulation to be transported through the apertures of the substrate of the microneedle array and then through the holes in the stratum corneum, while the microneedles are positioned in the holes.   
     
     
         27 . The method of  claim 26 , wherein at least one of the plurality of microneedles has a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion and in fluid communication with at least one of the apertures in the substrate. 
     
     
         28 . A method of transdermally collecting a biological fluid sample from a patient, comprising:
 inserting the microneedles of the device of  claim 20  into the skin of the patient to form holes in the stratum corneum; and   causing the biological fluid to be withdrawn from the patient through the holes in the stratum corneum and then through the apertures of the substrate of the microneedle array, while the microneedles are positioned in the holes.   
     
     
         29 . The method of  claim 28 , wherein at least one of the plurality of microneedles has a channel extending substantially from the base portion through at least a part of the body portion, the channel being open along at least part of the body portion and in fluid communication with at least one of the apertures in the substrate.