Microneedle Array Device and Method of Making

Abstract

A microneedle array device includes a substrate and an array of microneedles on the substrate. Each microneedle includes a redox enzyme and redox mediator and an electrically conductive layer on the substrate. The electrically conductive layer may extend partway up each microneedle exposing the tip thereof.

What is claimed is: 
     
         1 . A method of making a microneedle array device, the method comprising:
 forming an array of microneedles on a substrate, each microneedle made of hydrogel comprising a redox enzyme and a redox mediator; and   forming an electrically conductive layer on the substrate, the forming the electrically conductive layer comprising forming the electrically conductive layer to extend along a sidewall of each microneedle of the array of microneedles to a first height without covering a tip of a corresponding microneedle, the first height being between about 30% to about 90% of a height of the corresponding microneedle, the electrically conductive layer not extending into the corresponding microneedle, the electrically conductive layer not extending directly under the corresponding microneedle, and the tip of the corresponding microneedle not covered with the electrically conductive layer acting as a sensing area of the microneedle array device and as a shuttle path for electrons from the redox mediator through the hydrogel to the electrically conductive layer.   
     
     
         2 . The method according to  claim 1 , wherein each microneedle comprises a biocompatible hydrogel. 
     
     
         3 . The method according to  claim 1 , wherein the redox enzyme comprises at least one of glucose oxidase and lactate oxidase. 
     
     
         4 . The method according to  claim 1 , wherein the redox mediator comprises vinylferrocene. 
     
     
         5 . The method according to  claim 1 , wherein the redox mediator shifts between oxidized and reduced states and facilitates electron transfer during a reaction between an analyte and the redox enzyme in a physiological medium. 
     
     
         6 . The method according to  claim 1 , wherein forming the array of microneedles comprises forming the array of microneedles on the substrate by UV exposure through a mask. 
     
     
         7 . The method according to  claim 1 , wherein forming the electrically conductive layer further comprises:
 blanket forming an electrically conductive material over the array of microneedles and the substrate; and   patterning the electrically conductive material to form a plurality of openings therein, each opening exposing a tip of a respective microneedle, a remaining portion of the electrically conductive material forming the electrically conductive layer.   
     
     
         8 . A method of making a microneedle array device, the method comprising:
 forming a substrate;   forming an array of microneedles on the substrate, each microneedle made of hydrogel comprising a redox enzyme and a redox mediator; and   forming an electrically conductive layer on the substrate, the electrically conductive layer not extending into a corresponding microneedle, the electrically conductive layer not extending directly under the corresponding microneedle, and a tip of the corresponding microneedle not covered with the electrically conductive layer acting as a sensing area of the microneedle array device and as a shuttle path for electrons from the redox mediator through the hydrogel to the electrically conductive layer.   
     
     
         9 . The method of  claim 8 , wherein the electrically conductive layer extends along a sidewall of each microneedle of the array of microneedles to a first height without covering the tip of the corresponding microneedle, the first height being between about 30% to about 90% of a height of the corresponding microneedle. 
     
     
         10 . The method of  claim 8 , wherein the substrate comprises a flexible polymeric sheet selected from the group consisting of PET (polyethylene terephthalate), PEN (polyethylene naphthalate), PEEK (polyether ether ketone), PI (polyimide), silicones and siloxanes. 
     
     
         11 . The method of  claim 8 , wherein the redox mediator shifts between oxidized and reduced states and facilitates electron transfer during a reaction between an analyte and the redox enzyme in a physiological medium. 
     
     
         12 . The method of  claim 11 , wherein the analyte comprises at least one of glucose or lactate. 
     
     
         13 . The method of  claim 8 , wherein each microneedle is configured to cause indentation into a body tissue. 
     
     
         14 . The method of  claim 8 , wherein the redox mediator comprises vinylferrocene. 
     
     
         15 . A method of making a microneedle array device, the method comprising:
 forming a substrate;   forming an array of microneedles disposed on the substrate, each microneedle made of hydrogel comprising a redox enzyme and a redox mediator, the redox mediator configured to shift between oxidized and reduced states and facilitate electron transfer during a reaction between an analyte and the redox enzyme in a physiological medium; and   forming an electrically conductive layer on the substrate, the electrically conductive layer partially covering a sidewall of each microneedle of the array of microneedles without covering a tip of a corresponding microneedle, the electrically conductive layer not extending into the corresponding microneedle, the electrically conductive layer not extending directly under the corresponding microneedle, and the tip of the corresponding microneedle not covered with the electrically conductive layer acting as a sensing area of the microneedle array device and as a shuttle path for electrons from the redox mediator through the hydrogel to the electrically conductive layer.   
     
     
         16 . The method of  claim 15 , wherein each microneedle comprises a hydrogel substrate that comprises the redox enzyme and the redox mediator. 
     
     
         17 . The method of  claim 16 , wherein the hydrogel comprises a biocompatible and photodefinable hydrogel, the biocompatible and photodefinable hydrogel comprising:
 a monomer, an oligomer, a prepolymer, or a combination thereof;   a binder; and   photo-active materials (PAC) or photoinitiators (PhI).   
     
     
         18 . The method of  claim 15 , wherein each microneedle is configured to cause indentation into a body tissue. 
     
     
         19 . The method of  claim 15 , wherein the redox enzyme comprises at least one of glucose oxidase and lactate oxidase. 
     
     
         20 . The method of  claim 15 , wherein the redox mediator is selected from the group consisting of vinylferrocene, ferrocene derivatives, ferricyanide, conducting organic salts comprising tetrathiafulvalene-tetracyanoquinodimethane, TTF-TCNQ, quinone compounds, transition-metal complexes, phenothiazine and phenoxazine compounds, and osmium bipyridine complexes.