{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:09:37Z","timestamp":1762866577426,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T00:00:00Z","timestamp":1423699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Flexible iridium oxide (IrOx)-based micro-electrodes were fabricated on flexible polyimide substrates using a sol-gel deposition process for utilization as integrated  pseudo-reference electrodes for bio-electrochemical sensing applications. The fabrication method yields reliable miniature on-probe IrOx electrodes with long lifetime, high stability and repeatability. Such sensors can be used for long-term measurements. Various dimensions of sol-gel iridium oxide electrodes including 1 mm \u00d7 1 mm, 500 \u00b5m \u00d7 500 \u00b5m, and  100 \u00b5m \u00d7 100 \u00b5m were fabricated. Sensor longevity and pH dependence were investigated by immersing the electrodes in hydrochloric acid, fetal bovine serum (FBS), and  sodium hydroxide solutions for 30 days. Less pH dependent responses, compared to IrOx electrodes fabricated by electrochemical deposition processes, were measured at  58.8 \u00b1 0.4 mV\/pH, 53.8 \u00b1 1.3 mV\/pH and 48 \u00b1 0.6 mV\/pH, respectively. The on-probe IrOx pseudo-reference electrodes were utilized for dopamine sensing. The baseline responses of the sensors were higher than the one using an external Ag\/AgCl reference electrode. Using IrOx reference electrodes integrated on the same probe with working electrodes eliminated the use of cytotoxic Ag\/AgCl reference electrode without loss in sensitivity. This enables employing such sensors in long-term recording of concentrations of neurotransmitters in central nervous systems of animals and humans.<\/jats:p>","DOI":"10.3390\/s150204212","type":"journal-article","created":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T12:08:24Z","timestamp":1423742904000},"page":"4212-4228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Sol-Gel Deposition of Iridium Oxide for  Biomedical Micro-Devices"],"prefix":"10.3390","volume":"15","author":[{"given":"Cuong","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Electrical Engineering, University of Texas, Arlington, TX 76019, USA"}]},{"given":"Smitha","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, University of Texas, Arlington, TX 76019, USA"}]},{"given":"Xuesong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, University of Texas, Arlington, TX 76019, USA"}]},{"given":"Souvik","family":"Dubey","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, University of Texas, Arlington, TX 76019, USA"}]},{"given":"Jeffrey","family":"Mays","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, University of Texas, Arlington, TX 76019, USA"}]},{"given":"Hung","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, ETS, Montreal, QC H3C 1K3, Canada"}]},{"given":"Jung-Chih","family":"Chiao","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, University of Texas, Arlington, TX 76019, USA"}]}],"member":"1968","published-online":{"date-parts":[[2015,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/0003-2670(93)85008-8","article-title":"A Needle-Type Enzyme-Based Lactate Sensor for in Vivo Monitoring","volume":"281","author":"Hu","year":"1993","journal-title":"Anal. Chim. Acta."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1021\/ac00093a011","article-title":"Highly Selective Membrane-Free, Mediator-Free Glucose Biosensor","volume":"66","author":"Wang","year":"1994","journal-title":"Anal. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1109\/JSEN.2011.2173674","article-title":"An Integrated Flexible Implantable Micro-Probe for Sensing Neurotransmitters","volume":"12","author":"Cao","year":"2012","journal-title":"IEEE Sensors J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jelechem.2012.07.014","article-title":"Implantable Microprobe with Arrayed Microsensors for Combined Amperometric Monitoring of the Neurotransmitters, Glutamate and Dopamine","volume":"682","author":"Tseng","year":"2012","journal-title":"J. Electroanal. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Weltin, A., Enderle, B., Kieninger, J., and Urban, G.A. (2013, January 3\u20136). A Novel Multiparametric Flexible Microsensor for Metabolic Monitoring in Vivo. Baltimore, MD, USA.","DOI":"10.1109\/ICSENS.2013.6688341"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5093","DOI":"10.1021\/ac990636c","article-title":"Monitoring Glutamate and Ascorbate in the Extracellular Space of Brain Tissue with Electrochemical Microsensors","volume":"71","author":"Kulagina","year":"1999","journal-title":"Anal. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1109\/JSEN.2011.2107738","article-title":"A Passive Radio-Frequency pH-Sensing Tag for Wireless Food-Quality Monitoring","volume":"12","author":"Huang","year":"2012","journal-title":"IEEE Sensors J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3857","DOI":"10.1109\/JSEN.2012.2236551","article-title":"A Sol-Gel Iridium Oxide Based pH Sensor Array on Flexible Polyimide Substrate","volume":"13","author":"Nguyen","year":"2013","journal-title":"IEEE Sensors J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5570","DOI":"10.1021\/am301452b","article-title":"Gold Nanostructures on Flexible Substrates as Electrochemical Dopamine Sensors","volume":"4","author":"Hsu","year":"2012","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0003-2670(02)01511-8","article-title":"Sol\u2013Gel Derived Metal Dispersed Ceramic\u2013Graphite Composite Electrode for Amperometric Determination of Dopamine","volume":"478","author":"Uehara","year":"2003","journal-title":"Anal. Chim. Acta."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.bios.2006.09.017","article-title":"Towards the Silicon Nanowire-Based Sensor for Intracellular Biochemical Detection","volume":"22","author":"Park","year":"2007","journal-title":"Biosens. Bioelectron."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.3390\/s8085023","article-title":"Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo","volume":"8","author":"Wassum","year":"2008","journal-title":"Sensors"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1039\/B603561B","article-title":"A capillary-PDMS Hybrid Chip for Separations-Based Sensing of Neurotransmitters in Vivo","volume":"6","author":"Cellar","year":"2006","journal-title":"Lab Chip."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.3390\/s100301679","article-title":"Microfabricated Reference Electrodes and Their Biosensing Applications","volume":"10","author":"Shinwari","year":"2010","journal-title":"Sensors"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S0013-4686(00)00644-7","article-title":"Use of Polypyrrole Film Containing Fe(CN)63\u2212 as Pseudo-Reference Electrode: Application for Amperometric Biosensors","volume":"46","author":"Gros","year":"2001","journal-title":"Electrochim. Acta."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/elan.1140080713","article-title":"Miniaturized Reference Electrodes with Microporous Polymer Junctions","volume":"8","author":"Pedrotti","year":"1996","journal-title":"Electroanalysis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.bios.2012.10.061","article-title":"Electrochemically Deposited Iridium Oxide Reference Electrode Integrated with an Electroenzymatic Glutamate Sensor on a Multi-Electrode Arraymicroprobe","volume":"42","author":"Tolosa","year":"2013","journal-title":"Biosens. Bioelectron."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.sna.2011.05.016","article-title":"A Flexible pH Sensor Based on the Iridium Oxide Sensing Film","volume":"169","author":"Huang","year":"2011","journal-title":"Sens. Actuators A Phys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0003-2670(02)00334-3","article-title":"Development of a Micro-Planar Ag\/AgCl Quasi-Reference Electrode with Long-Term Stability for an Amperometric Glucose Sensor","volume":"462","author":"Matsumoto","year":"2002","journal-title":"Anal. Chim. Acta."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1109\/JSEN.2003.814649","article-title":"Application of a New Cl-Plasma-Treated Ag\/AgCl Reference Electrode to Micromachined Glucose Sensor","volume":"3","author":"Park","year":"2003","journal-title":"IEEE Sensors J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1021\/ac00077a015","article-title":"Prevention of the Rapid Degradation of Subcutaneously Implanted Ag\/AgCl Reference Electrodes Using Polymer Coatings","volume":"66","author":"Moussy","year":"1994","journal-title":"Anal. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1161\/01.RES.53.1.105","article-title":"Toxic Effects of Silver-Silver Chloride Electrodes on Vascular Smooth Muscle","volume":"53","author":"Jackson","year":"1983","journal-title":"Circ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/0956-5663(91)87018-7","article-title":"Application of Cell Culture Toxicity Tests to the Development of Implantable Biosensors","volume":"6","author":"Zhang","year":"1991","journal-title":"Biosens. Bioelectron."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1109\/10.846685","article-title":"Chronic Neural Stimulation with Thin-Film, Iridium Oxide Electrodes","volume":"47","author":"Weiland","year":"2000","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1109\/TBME.2002.805487","article-title":"In Vitro Electrical Properties for Iridium Oxide Versus Titanium Nitride Stimulating Electrodes","volume":"49","author":"Weiland","year":"2002","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E226","DOI":"10.1149\/1.1747881","article-title":"Sputtered Iridium Oxide Films as Charge Injection Material for Functional Electrostimulation","volume":"151","author":"Slavcheva","year":"2004","journal-title":"J. Electrochem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1016\/S0142-9612(03)00025-5","article-title":"Biocompatibility and Charge Injection Property of Iridium Film Formed by Ion Beam Assisted Deposition","volume":"24","author":"Lee","year":"2003","journal-title":"Biomaterials"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S0925-4005(00)00650-X","article-title":"In Vitro and in Vivo Measurements of Fiber Optic and Electrochemical Sensors to Monitor Brain Tissue pH","volume":"72","author":"Grant","year":"2001","journal-title":"Sens. Actuators B Chem."},{"key":"ref_29","unstructured":"Franklin, R.K., Johnson, M.D., Scottt, K., Shim, J.H., Nam, H., Kipke, D.R., and Brown, R.B. (November, January 30). Iridium Oxide Reference Electrodes for Neurochemical Sensing with MEMS Microelectrode Arrays. Irvine, CA, USA."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Inzelt, G. (2013). Handbook of Reference Electrodes, Springer.","DOI":"10.1007\/978-3-642-36188-3"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.bios.2006.05.033","article-title":"Differential pH Measurements of Metabolic Cellular Activity in Nl Culture Volumes using Microfabricated Iridium Oxide Electrodes","volume":"22","author":"Ges","year":"2007","journal-title":"Biosen. Bioelectron."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/0013-4686(94)00339-3","article-title":"Improved Durability of Iridium Oxide Coated Titanium Anode with Interlayers for Oxygen Evolution at High Current Densities","volume":"40","author":"Kamegaya","year":"1995","journal-title":"Electrochim. Acta."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1021\/ac0261404","article-title":"Improved Electrodeposited Iridium Oxide pH Sensor Fabricated on Etched Titanium Substrates","volume":"75","author":"Marzouk","year":"2003","journal-title":"Anal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0022-3093(94)90300-X","article-title":"Iridium Oxide Films via Sol-Gel Processing","volume":"178","author":"Osaka","year":"1994","journal-title":"J. Non-Cryst. Solids"},{"key":"ref_35","unstructured":"Bard, A.J., and Faulkner, L.R. (1980). Electrochemical Methods: Fundamentals and Applications, Wiley."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Thomas, F., and Henze, G. (2001). Introduction to Voltammetric Analysis: Theory and Practice, Csiro Publishing.","DOI":"10.1071\/9780643101135"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S1452-3981(23)14998-4","article-title":"Computational and Electrochemical Studies on the Redox Reaction of Dopamine in Aqueous Solution","volume":"6","author":"Ghaemi","year":"2011","journal-title":"Int. J. Electrochem. Sci."},{"key":"ref_38","first-page":"3357","article-title":"Amperometric Determination of Dopamine on a Glassy Carbon Electrode Chemically Modified with Cobalt Pentacyanonitrosylferrate","volume":"20","author":"Bari","year":"2008","journal-title":"Asian J. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1039\/a704508e","article-title":"Biosensor for Neurotransmitter L-Glutamic Acid Designed for Efficient Use of L-Glutamate Oxidase and Effective Rejection of Interference","volume":"122","author":"Ryan","year":"1997","journal-title":"Analyst."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1109\/TBME.2005.862572","article-title":"Potential-Biased Asymmetric Waveforms for Charge-Injection with Activated Iridium Oxide (AIROF) Neural Stimulation Electrodes","volume":"53","author":"Cogan","year":"2006","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1116\/1.576313","article-title":"Morphology and Charge Capacity of Sputtered Iridium Oxide Films","volume":"7","author":"Klein","year":"1989","journal-title":"J. Vac. Sci. Technol. A."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00604-011-0614-3","article-title":"Gold Electrodes Modified with Gold Nanoparticles and Thio Compounds for Electrochemical Sensing of Dopamine Alone and in Presence of Potential Interferents. A Comparative Study","volume":"174","author":"Luczak","year":"2011","journal-title":"Microchim. Acta."},{"key":"ref_43","unstructured":"Arumugam, P., Siddiqui, S., Zeng, H., and Carlisle, J.A. (2013). Biosensors Based on Nanomaterials and Nanodevices, CRC Press."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Li, G., and Miao, P. (2013). Electrochemical Analysis of Proteins and Cells, Springer.","DOI":"10.1007\/978-3-642-34252-3"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/jbm.b.31223","article-title":"Sputtered Iridium Oxide Films for Neural Stimulation Electrodes","volume":"89","author":"Cogan","year":"2009","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4103\/2229-5186.79345","article-title":"Methods for the Determination of Limit of Detection and Limit of Quantitation of the Analytical Methods","volume":"2","author":"Shrivastava","year":"2011","journal-title":"Chron. Young Sci."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/15\/2\/4212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:42:36Z","timestamp":1760215356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/15\/2\/4212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,12]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,2]]}},"alternative-id":["s150204212"],"URL":"https:\/\/doi.org\/10.3390\/s150204212","relation":{},"ISSN":["1424-8220"],"issn-type":[{"type":"electronic","value":"1424-8220"}],"subject":[],"published":{"date-parts":[[2015,2,12]]}}}