Hollow Microneedle-based Sensor for Multiplexed Transdermal Electrochemical Sensing

Summary

This article details the construction of a multiplexed microneedle-based sensor. The device is being developed for in situ sampling and electrochemical analysis of multiple analytes in a rapid and selective manner. We envision clinical medicine and biomedical research uses for these microneedle-based sensors.

Abstract

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals suffering from chronic medical conditions facile assessment of their immediate physiological state. Furthermore, it could serve as a research tool for analysis of complex, multifactorial medical conditions. In order for such a multianalyte sensor to be realized, it must be minimally invasive, sampling of interstitial fluid must occur without pain or harm to the user, and analysis must be rapid as well as selective.

Initially developed for pain-free drug delivery, microneedles have been used to deliver vaccines and pharmacologic agents (e.g., insulin) through the skin.^1-2 Since these devices access the interstitial space, microneedles that are integrated with microelectrodes can be used as transdermal electrochemical sensors. Selective detection of glucose, glutamate, lactate, hydrogen peroxide, and ascorbic acid has been demonstrated using integrated microneedle-electrode devices with carbon fibers, modified carbon pastes, and platinum-coated polymer microneedles serving as transducing elements.^3-7,8

This microneedle sensor technology has enabled a novel and sophisticated analytical approach for in situ and simultaneous detection of multiple analytes. Multiplexing offers the possibility of monitoring complex microenvironments, which are otherwise difficult to characterize in a rapid and minimally invasive manner. For example, this technology could be utilized for simultaneous monitoring of extracellular levels of, glucose, lactate and pH,⁹ which are important metabolic indicators of disease states^7,10-14 (e.g., cancer proliferation) and exercise-induced acidosis.¹⁵

Protocol

1. Microneedle Fabrication

1. Using three-dimensional modeling software Solidworks (Dassault Systemes SA, Velizy, France), design a pyramidal-shaped hollow microneedle array (Figure 1).^3-5
2. Design a support structure for the microneedle array using Magics RP 13 software (Materialise NV, Leuven, Belgium). The support structure allows the resin to drain from the device during fabrication and provides a base on which the microneedles are built. An example support structure is shown in Figure 1.
3. The linked support and microneedle array files are uploaded into the Perfactory RP software (EnvisionTEC G....

Discussion

Multiple aspects of the design of this microneedle-based sensor were considered prior to device fabrication. In order to use this sensor for real-time detection, the response time of the sensor must be low; in this protocol, each tested sensor exhibited a response time below fifteen seconds. Pastes used in this protocol were also chosen for their selectivity within in vivo environments, which contain electroactive biomolecules that can interfere with electrode response. In addition to paste composition, th.......