Sandia is multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United Stated Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000. The authors acknowledge funding from Sandia National Laboratories' Laboratory Directed Research &amp; Development (LDRD) program.

1. Microneedle Fabrication
<ol>
	<li>Using three-dimensional modeling software Solidworks (Dassault Systemes SA, Velizy, France), design a pyramidal-shaped hollow microneedle array (Figure 1).3-5</li>
	<li>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 sh...

<ol>
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W., Liepmann, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In-device+enzyme+immobilization:+Wafer-level+fabrication+of+an+integrated+glucose.">In-device enzyme immobilization: Wafer-level fabrication of an integrated glucose.</a> Sens. Actuat. B. 99, 163-173 (2004).</li><li>Miller, P. R., Skoog, S. A., Edwards, T. L., Lopez, D. M., Wheeler, D. R., Arango, D. C., Xiao, X., Brozik, S. M., Wang, J., Polsky, R., Narayan, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiplexed+microneedle-based+biosensor+array+for+characterization+of+metabolic+acidosis.">Multiplexed microneedle-based biosensor array for characterization of metabolic acidosis.</a> Biomicrofluidics. 88, 739-742 (2012).</li><li>Miller, P. R., Skoog, S. A., Edwards, T. L., Lopez, D. M., Wheeler, D. R., Arango, D. C., Xiao, X., Brozik, S. M., Wang, J., Polsky, R., Narayan, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiplexed+microneedle-based+biosensor+array+for+characterization+of+metabolic+acidosis.">Multiplexed microneedle-based biosensor array for characterization of metabolic acidosis.</a> Talanta. 88, 739-742 (2012).</li><li>Rofstad, E. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microenvironment-induced+cancer+metastasis.">Microenvironment-induced cancer metastasis.</a> Int. J. Radiat. Biol. 76, 589-605 (2000).</li><li>Vander Heiden, M. G., Cantley, L. C., Thompson, C. 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A., Ghiasvand, F., Parker, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Biochemistry+of+exercise-induced+metabolic+acidosis.">Biochemistry of exercise-induced metabolic acidosis.</a> Am. J. Phys. 287, R502-R516 (2004).</li><li>Wang, J., Liu, J., Chen, L., Lu, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+selective+membrane-free,+mediator-free+glucose+biosensor.">Highly selective membrane-free, mediator-free glucose biosensor.</a> Anal. Chem. 66, 3600-3603 (1994).</li><li>Makos, M. A., Omiatek, D. M., Ewing, A. G., Heien, M. 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No conflicts of interest declared.

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...

<table border="1">
 <tbody>
 <tr>
 <td>Name of the reagent</td>
 <td>Company</td>
 <td>Catalogue number</td>
 </tr>
 <tr>
 <td>Flat flexible cable</td>
 <td>Molex</td>
 <td>3302/10SF</td>
 </tr>
 <tr>
 <td>0.003" Side sided tape</td>
 <td>Melinex</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>0.004" Double sided tape</td>
 <td>Melinex</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Lactate oxidase</td>
 <td>Sigma</td>
 <td>L0638</td>
 </tr>
 <tr>
 <td>Glucose oxidase</td>
 <td>Sigma</td>
 <td>G7141</td>
 </tr>
 <tr>
 <td>Rhodium on carbon</td>
 <td>Sigma</td>
 <td>206164</td>
 </tr>
 <tr>
 <td>Graphite powder</td>
 <td>Sigma</td>
 <td>385031000</td>
 </tr>
 <tr>
 <td>poly(ethylenimine)</td>
 <td>Acros</td>
 <td>178570010</td>
 </tr>
 <tr>
 <td>Mineral oil </td>
 <td>Sigma</td>
 <td>M5904</td>
 </tr>
 <tr>
 <td>Glucose</td>
 <td>Sigma</td>
 <td>G8270</td>
 </tr>
 <tr>
 <td>Lactate</td>
 <td>Sigma</td>
 <td>L1750</td>
 </tr>
 <tr>
 <td>Fast Blue RR salt</td>
 <td>Sigma</td>
 <td>F0500</td>
 </tr>
 <tr>
 <td>e-Shell 300</td>
 <td>EnvisionTEC</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>e-Shell 200</td>
 <td>EnvisionTEC</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Ag/AgCl reference electrode</td>
 <td>Basi</td>
 <td>MF-2052</td>
 </tr>
 <tr>
 <td>Pt wire</td>
 <td>Basi</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>PGSTAT12 AutolabPotentiostat </td>
 <td>EcoChemie</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Perfactory RP</td>
 <td>EnvisionTEC</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Ottoflash Postcuring system</td>
 <td>EnvisionTEC</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Phosphoric acid</td>
 <td>Fisher</td>
 <td>A366-4</td>
 </tr>
 <tr>
 <td>60W Model 6.75 CO2 raster/vector laser system </td>
 <td>Universal Laser Systems</td>
 <td>PLS6.75</td>
 </tr>
 <tr>
 <td>CorelDraw</td>
 <td>Corel</td>
 <td>&nbsp;</td>
 </tr>
 <tr>
 <td>Solidworks </td>
 <td>Dassault Systemes</td>
 <td>2009</td>
 </tr>
 <tr>
 <td>Magics RP13</td>
 <td>Materialise </td>
 <td>&nbsp;</td>
 </tr>
 </tbody>
</table>

hollow microneedle-based sensor for multiplexed transdermal electrochemical sensing

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 states7,10-14 (e.g., cancer proliferation) and exercise-induced acidosis.15

Watch this Scientific Journal Video about Hollow Microneedle-based Sensor for Multiplexed Transdermal Electrochemical Sensing at JoVE.com

Hollow Microneedle-based Sensor for Multiplexed Transdermal Electrochemical Sensing

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.

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals ...

hollow-microneedle-based-sensor-for-multiplexed-transdermal

Research

JoVE Journal

Bioengineering

14.2K visualizações.  University of North Carolina and North Carolina State University. Este artigo detalha a construção de um sensor de microagulhas multiplexados baseado. O dispositivo está a ser desenvolvido para a amostragem in situ ea análise electroquímica de analitos múltiplos de uma maneira rápida e selectiva. Nós encaramos a medicina clínica e pesquisa biomédica usa para esses sensores baseados microagulhas.