{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:35:04Z","timestamp":1787880904891,"version":"build-2784847793"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["03VP11340"],"award-info":[{"award-number":["03VP11340"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["EXC 2033\u2013390677874\u2013RESOLV"],"award-info":[{"award-number":["EXC 2033\u2013390677874\u2013RESOLV"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsche Forschungsgemeinschaft","award":["03VP11340"],"award-info":[{"award-number":["03VP11340"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["EXC 2033\u2013390677874\u2013RESOLV"],"award-info":[{"award-number":["EXC 2033\u2013390677874\u2013RESOLV"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>With the goal of fast and accurate diagnosis of infectious diseases, this study presents a novel electrochemical biosensor that employs a refined aptamer (C9t) for the detection of spike (S) protein SARS-CoV-2 variants in a flexible multielectrode aptasensor array with PoC capabilities. Two aptamer modifications were employed: removing the primer binding sites and including two dithiol phosphoramidite anchor molecules. Thus, reducing fabrication time from 24 to 3 h and increasing the stability and sparseness for multi-thiol aptasensors compared to a standard aptasensor using single thiols, without a reduction in aptamer density. The biosensor fabrication, optimization, and detection were verified in detail by electrochemistry, QCM-D, SPR, and XPS. The analyte\u2013receptor binding was further confirmed spectroscopically at the level of individual molecules by AFM-IR. The aptasensor possesses a low limit of detection (8.0 fg\/mL), the highest sensitivity reported for S protein (209.5 signal per concentration decade), and a wide dynamic detection range (8.0 fg\/mL\u201338 ng\/mL) in nasopharyngeal samples, covering the clinically relevant range. Furthermore, the C9t aptasensor showed high selectivity for SARS-CoV-2 S proteins over biomarkers for MERS-CoV, RSV, and Influenza. Even more, it showed a three times higher sensitivity for the Omicron in comparison to the Wuhan strain (wild type), alpha, and beta variants of the SARS-CoV-2 virus. Those results demonstrate the creation of an affordable and variant-selective refined C9t aptasensor that outperformed current rapid diagnosis tests.<\/jats:p>","DOI":"10.3390\/bios15010024","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T06:43:04Z","timestamp":1736145784000},"page":"24","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Truncated Multi-Thiol Aptamer-Based SARS-CoV-2 Electrochemical Biosensor: Towards Variant-Specific Point-of-Care Detection with Optimized Fabrication"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0504-9263","authenticated-orcid":false,"given":"Sergio Roberto","family":"Molina Ramirez","sequence":"first","affiliation":[{"name":"Institute of Biological Information Processing, Bioelectronics (IBI-3), Forschungszentrum J\u00fclich GmbH, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6532-4603","authenticated-orcid":false,"given":"Nafiseh","family":"Samiseresht","sequence":"additional","affiliation":[{"name":"Department of Interface Chemistry and Surface Engineering, Max Planck Institute for Sustainable Materials GmbH, 40237 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5401-4211","authenticated-orcid":false,"given":"Mateo Alejandro","family":"Mart\u00ednez-Roque","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Bioelectronics (IBI-3), Forschungszentrum J\u00fclich GmbH, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinando","family":"Catania","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Bioelectronics (IBI-3), Forschungszentrum J\u00fclich GmbH, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3160-0054","authenticated-orcid":false,"given":"Kevin","family":"Graef","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Bioelectronics (IBI-3), Forschungszentrum J\u00fclich GmbH, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-5355","authenticated-orcid":false,"given":"Martin","family":"Rabe","sequence":"additional","affiliation":[{"name":"Department of Interface Chemistry and Surface Engineering, Max Planck Institute for Sustainable Materials GmbH, 40237 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-2702","authenticated-orcid":false,"given":"Andreas","family":"Offenh\u00e4usser","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Bioelectronics (IBI-3), Forschungszentrum J\u00fclich GmbH, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1296-8265","authenticated-orcid":false,"given":"Dirk","family":"Mayer","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Bioelectronics (IBI-3), Forschungszentrum J\u00fclich GmbH, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-5547","authenticated-orcid":false,"given":"Gabriela","family":"Figueroa-Miranda","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Bioelectronics (IBI-3), Forschungszentrum J\u00fclich GmbH, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"955","DOI":"10.4269\/ajtmh.20-0849","article-title":"The Origin of COVID-19 and Why It Matters","volume":"103","author":"Morens","year":"2020","journal-title":"Am. 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