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In this study, we developed an impedimetric EBV biosensor designed for practical and early screening, based on mimicking the virus\u2019s natural infection mechanism. To achieve this, the B cell surface protein CD21\u2014serving as the host receptor\u2014was immobilized onto a carbon screen-printed electrode. The interaction between CD21 and the EBV surface glycoprotein gp350 was monitored using electrochemical impedance spectroscopy. Following the optimization of experimental parameters, the biosensor\u2019s analytical performance was evaluated. It exhibited a linear detection range from 5 to 100\u00a0ng\/mL, with a limit of detection of 0.0074\u00a0ng\/mL, a limit of quantification of 0.022\u00a0ng\/mL, and a relative standard deviation of 1.34%. The optimized biosensor was then tested using 1:100 diluted saliva samples collected from healthy individuals, yielding highly promising results that support its potential for real-world applications.<\/jats:p>","DOI":"10.1038\/s41598-025-13030-2","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T09:31:03Z","timestamp":1754040663000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of Epstein Barr virus biosensor by mimicking its infection mechanism for early detection of multiple sclerosis"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3607-7208","authenticated-orcid":false,"given":"\u00dclk\u00fc","family":"Anik","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nil Su","family":"\u00c7aylayik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"13030_CR1","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.3390\/v14112372","volume":"14","author":"GL Bu","year":"2022","unstructured":"Bu, G. L., Xie, C., Kang, Y. F., Zeng, M. S. & Sun, C. How EBV infects: The tropism and underlying molecular mechanism for viral infection. Viruses 14, 2372 https:\/\/doi.org\/10.3390\/v14112372 (2022).","journal-title":"Viruses"},{"key":"13030_CR2","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s41586-022-04432-7","volume":"603","author":"TV Lanz","year":"2022","unstructured":"Lanz, T. V. et al. Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GLialCAM. Nature 603, 321\u2013327 (2022).","journal-title":"Nature"},{"key":"13030_CR3","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1002\/ana.24088","volume":"75","author":"J Bankoti","year":"2014","unstructured":"Bankoti, J. et al. In multiple sclerosis, oligoclonal bands connect to peripheral B-cell responses. Ann. Neurol. 75, 266\u2013276 (2014).","journal-title":"Ann. 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Lancet Neurol. 22, 338\u2013349. https:\/\/doi.org\/10.1016\/S1474-4422(22)00471-9 (2023).","journal-title":"Lancet Neurol."},{"key":"13030_CR6","doi-asserted-by":"publisher","first-page":"e0226436","DOI":"10.1371\/journal.pone.0226436","volume":"14","author":"K Rostgaard","year":"2019","unstructured":"Rostgaard, K. et al. Primary Epstein-Barr virus infection with and without infectious mononucleosis. PLoS ONE 14, e0226436 (2019).","journal-title":"PLoS ONE"},{"key":"13030_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0012496","volume":"5","author":"AE Handel","year":"2010","unstructured":"Handel, A. E. et al. An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS ONE 5, 1\u20135 (2010).","journal-title":"PLoS ONE"},{"key":"13030_CR8","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1158\/0008-5472.CAN-06-3566","volume":"67","author":"H Hjalgrim","year":"2007","unstructured":"Hjalgrim, H. et al. 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The remaining authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28089"}}