{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T22:10:47Z","timestamp":1772057447047,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,6,9]],"date-time":"2018-06-09T00:00:00Z","timestamp":1528502400000},"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>For analytical applications involving label-free biosensors and multiple measurements, i.e., across an electrode array, it is essential to develop complete sensor systems capable of functionalization and of producing highly consistent responses. To achieve this, a multi-microelectrode device bearing twenty-four equivalent 50 \u00b5m diameter Pt disc microelectrodes was designed in an integrated 3-electrode system configuration and then fabricated. Cyclic voltammetry and electrochemical impedance spectroscopy were used for initial electrochemical characterization of the individual working electrodes. These confirmed the expected consistency of performance with a high degree of measurement reproducibility for each microelectrode across the array. With the aim of assessing the potential for production of an enhanced multi-electrode sensor for biomedical use, the working electrodes were then functionalized with 6-mercapto-1-hexanol (MCH). This is a well-known and commonly employed surface modification process, which involves the same principles of thiol attachment chemistry and self-assembled monolayer (SAM) formation commonly employed in the functionalization of electrodes and the formation of biosensors. Following this SAM formation, the reproducibility of the observed electrochemical signal between electrodes was seen to decrease markedly, compromising the ability to achieve consistent analytical measurements from the sensor array following this relatively simple and well-established surface modification. To successfully and consistently functionalize the sensors, it was necessary to dilute the constituent molecules by a factor of ten thousand to support adequate SAM formation on microelectrodes. The use of this multi-electrode device therefore demonstrates in a high throughput manner irreproducibility in the SAM formation process at the higher concentration, even though these electrodes are apparently functionalized simultaneously in the same film formation environment, confirming that the often seen significant electrode-to-electrode variation in label-free SAM biosensing films formed under such conditions is not likely to be due to variation in film deposition conditions, but rather kinetically controlled variation in the SAM layer formation process at these microelectrodes.<\/jats:p>","DOI":"10.3390\/s18061891","type":"journal-article","created":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T11:01:01Z","timestamp":1528714861000},"page":"1891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Microelectrode Array with Reproducible Performance Shows Loss of Consistency Following Functionalization with a Self-Assembled 6-Mercapto-1-hexanol Layer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4647-7483","authenticated-orcid":false,"given":"Damion K.","family":"Corrigan","sequence":"first","affiliation":[{"name":"EaStCHEM, School of Chemistry, The University of Edinburgh, Joseph Black Building, The King\u2019s Buildings, West Mains Road, Edinburgh EH9 3FJ, UK"},{"name":"Department of Biomedical Engineering, University of Strathclyde, Glasgow G4 0NS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Vezza","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Strathclyde, Glasgow G4 0NS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6446-2824","authenticated-orcid":false,"given":"Holger","family":"Schulze","sequence":"additional","affiliation":[{"name":"Division of Infection and Pathway Medicine, Edinburgh Medical School, The University of Edinburgh, Chancellor\u2019s Building, Little France Crescent, Edinburgh EH16 4SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Till T.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Division of Infection and Pathway Medicine, Edinburgh Medical School, The University of Edinburgh, Chancellor\u2019s Building, Little France Crescent, Edinburgh EH16 4SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Mount","sequence":"additional","affiliation":[{"name":"EaStCHEM, School of Chemistry, The University of Edinburgh, Joseph Black Building, The King\u2019s Buildings, West Mains Road, Edinburgh EH9 3FJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8110-2230","authenticated-orcid":false,"given":"Anthony J.","family":"Walton","sequence":"additional","affiliation":[{"name":"Institute for Integrated Micro and Nano Systems, School of Engineering, The University of Edinburgh, The King\u2019s Buildings, Alexander Crum Brown Road, Edinburgh EH9 3FF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4012-9330","authenticated-orcid":false,"given":"Jonathan G.","family":"Terry","sequence":"additional","affiliation":[{"name":"Institute for Integrated Micro and Nano Systems, School of Engineering, The University of Edinburgh, The King\u2019s Buildings, Alexander Crum Brown Road, Edinburgh EH9 3FF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1211\/jpp.61.04.0017","article-title":"Reichardt\u2019s Dye and Its Reactions with the Alkylating Agents 4-Chloro-1-Butanol, Ethyl Methanesulfonate, 1-Bromobutane and Fast Red B\u2014A Potentially Useful Reagent for the Detection of Genotoxic Impurities in Pharmaceuticals","volume":"61","author":"Corrigan","year":"2009","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1111\/j.2042-7158.2010.01152.x","article-title":"Towards the Development of a Rapid, Portable, Surface Enhanced Raman Spectroscopy Based Cleaning Verification System for the Drug Nelarabine","volume":"62","author":"Corrigan","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mutilba, U., Gomez-Acedo, E., Kortaberria, G., Olarra, A., and Yag\u00fce-Fabra, J.A. (2017). Traceability of on-Machine Tool Measurement: A Review. Sensors, 17.","DOI":"10.20944\/preprints201705.0021.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1039\/b410006a","article-title":"On-Chip Generated Mercury Microelectrode for Heavy Metal Ion Detection","volume":"5","author":"Zhu","year":"2005","journal-title":"Lab Chip"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17275","DOI":"10.3390\/s140917275","article-title":"Raman Spectroscopy for in-Line Water Quality Monitoring\u2014Instrumentation and Potential","volume":"14","author":"Li","year":"2014","journal-title":"Sensors"},{"key":"ref_6","first-page":"699","article-title":"In Situ Bismuth Film Modified Carbon Fiber Microelectrode for Nanomolar Detection of Cadmium and Lead","volume":"51","author":"Anandhakumar","year":"2012","journal-title":"Indian J. Chem. Sect. A Inorg. Phys. Theor. Anal. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/adfm.201702891","article-title":"Recent Advances in Sensing Applications of Graphene Assemblies and Their Composites","volume":"27","author":"Tung","year":"2017","journal-title":"Adv. Funct. Mater."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.bios.2016.07.075","article-title":"Amperometric IFN-\u03b3 Immunosensors with Commercially Fabricated PCB Sensing Electrodes","volume":"86","author":"Moschou","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bios.2013.02.045","article-title":"Development of Electrochemical Immunosensors towards Point of Care Diagnostics","volume":"47","author":"Wan","year":"2013","journal-title":"Biosens. Bioelectron."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.bios.2017.10.048","article-title":"Highly Sensitive Electrochemical Nuclear Factor Kappa B Aptasensor Based on Target-Induced Dual-Signal Ratiometric and Polymerase-Assisted Protein Recycling Amplification Strategy","volume":"102","author":"Peng","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pasinszki, T., Krebsz, M., Tung, T.T., and Losic, D. (2017). Carbon Nanomaterial Based Biosensors for Non-Invasive Detection of Cancer and Disease Biomarkers for Clinical Diagnosis. Sensors, 17.","DOI":"10.3390\/s17081919"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1039\/cs9942300289","article-title":"Microelectrodes: New Dimensions in Electrochemistry","volume":"23","author":"Forster","year":"1994","journal-title":"Chem. Soc. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1002\/anie.199312681","article-title":"Ultramicroelectrodes in Electrochemistry","volume":"32","author":"Heinze","year":"1993","journal-title":"Agnew. Chem. Int. Ed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/smll.200801593","article-title":"Microelectrode Arrays for Electrochemistry: Approaches to Fabrication","volume":"5","author":"Compton","year":"2009","journal-title":"Small"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11342","DOI":"10.1021\/ac5030842","article-title":"Enhanced Electroanalysis in Lithium Potassium Eutectic (LKE) Using Microfabricated Square Microelectrodes","volume":"86","author":"Corrigan","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1039\/C6FD00002A","article-title":"Advances in Electroanalysis, Sensing and Monitoring in Molten Salts","volume":"190","author":"Corrigan","year":"2016","journal-title":"Faraday Discuss."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1109\/JMEMS.2015.2399106","article-title":"Development and Optimization of Durable Microelectrodes for Quantitative Electroanalysis in Molten Salt","volume":"24","author":"Blair","year":"2015","journal-title":"J. Microelectromech. Syst."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Temiz, Y., Ferretti, A., Leblebicib, Y., and Guiducci, C. (2012). A comparative study on fabrication techniques for on chip microelectrodes. Lab. Chip., 4920\u20134928.","DOI":"10.1039\/c2lc40582b"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0003-2670(01)01399-X","article-title":"Electrochemical Nucleic Acid Biosensors","volume":"469","author":"Wang","year":"2002","journal-title":"Anal. Chim. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9513","DOI":"10.3390\/s91209513","article-title":"DNA Hybridization Sensors Based on Electrochemical Impedance Spectroscopy as a Detection Tool","volume":"9","author":"Park","year":"2009","journal-title":"Sensors"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1007\/s00216-008-1970-7","article-title":"The Use of Electrochemical Impedance Spectroscopy for Biosensing","volume":"391","author":"Lisdat","year":"2008","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.1039\/c3an01319g","article-title":"Development of a PCR-Free Electrochemical Point of Care Test for Clinical Detection of Methicillin Resistant Staphylococcus Aureus (MRSA)","volume":"138","author":"Corrigan","year":"2013","journal-title":"Analyst"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jelechem.2016.12.050","article-title":"Improving Performance of a Rapid Electrochemical MRSA Assay: Optimisation of Assay Conditions to Achieve Enhanced Discrimination of Clinically Important DNA Sequences under Ambient Conditions","volume":"786","author":"Corrigan","year":"2017","journal-title":"J. Electroanal. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7867","DOI":"10.1021\/ac501800q","article-title":"Impedimetric DNA Detection-Steps Forward to Sensorial Application","volume":"86","author":"Riedel","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1039\/C7AN01590A","article-title":"PNA versus DNA in Electrochemical Gene Sensing Based on Conducting Polymers: Study of Charge and Surface Blocking Effects on the Sensor Signal","volume":"143","author":"Zhu","year":"2018","journal-title":"Analyst"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1039\/C7AN90048A","article-title":"Impedimetric Measurement of DNA\u2013DNA Hybridisation Using Microelectrodes with Different Radii for Detection of Methicillin Resistant Staphylococcus Aureus (MRSA)","volume":"142","author":"Li","year":"2017","journal-title":"Analyst"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bios.2013.11.067","article-title":"Development of Stable and Reproducible Biosensors Based on Electrochemical Impedance Spectroscopy: Three-Electrode versus Two-Electrode Setup","volume":"55","author":"Ianeselli","year":"2014","journal-title":"Biosens. Bioelectron."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1039\/b924342a","article-title":"The Development and Characterisation of Square Microfabricated Electrode Systems","volume":"135","author":"Woodvine","year":"2010","journal-title":"Analyst"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1016\/j.elecom.2007.10.008","article-title":"Self-Assembled Monolayers on Au Microelectrodes","volume":"9","author":"Sheffer","year":"2007","journal-title":"Electrochem. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1021\/ac50160a042","article-title":"Diffusion Coefficients of Ferri- and Ferrocyanide Ions in Aqueous Media, Using Twin-Electrode Thin-Layer Electrochemistry","volume":"42","author":"Konopka","year":"1970","journal-title":"Anal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.snb.2009.01.044","article-title":"Characterisation of Commercially Available Electrochemical Sensing Platforms","volume":"138","author":"Kadara","year":"2009","journal-title":"Sens. Actuators B Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.snb.2006.08.033","article-title":"Development of a Reliable Microelectrode Dissolved Oxygen Sensor","volume":"123","author":"Sosna","year":"2007","journal-title":"Sens. Actuators B Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9689","DOI":"10.1021\/la301281y","article-title":"A Dielectric Model of Self-Assembled Monolayer Interfaces by Capacitive Spectroscopy","volume":"28","author":"Rahman","year":"2012","journal-title":"Langmuir"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1049\/iet-nbt.2013.0049","article-title":"Nanoscale Electrode Arrays Produced with Microscale Lithographic Techniques for Use in Biomedical Sensing Applications","volume":"7","author":"Terry","year":"2013","journal-title":"IET Nanobiotechnol."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/18\/6\/1891\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:07:58Z","timestamp":1760195278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/18\/6\/1891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,9]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,6]]}},"alternative-id":["s18061891"],"URL":"https:\/\/doi.org\/10.3390\/s18061891","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,9]]}}}