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However, the lack of sensitive and noninvasive diagnostic approaches remains a major challenge. Herein, we developed an electrochemical biosensor for urinary miRNA-182 in bladder cancer detection based on the primer exchange reaction (PER) and CRISPR\/Cas12a one-pot cascade reaction. Specifically, the presence of the target miRNA-182 initiated the PER reaction to generate multiple CRISPR\/Cas12a activation sequences, which subsequently activated the trans-cleavage activity of CRISPR\/Cas12a and induced the cleavage of methylene-blue-labeled signal probes (SP-MB). The uncleaved SP-MB was captured by the complementary sequence (CS) immobilized on the electrode surface, generating an electrochemical response signal that decreased with increasing target concentration, thereby enabling the quantitative detection of miRNA-182. Notably, the detection performance of biosensors constructed on different DNA nanostructure-modified interfaces (S, H, TDN, and TDR) containing CS was systematically compared to elucidate the regulatory mechanism of the biosensing interface. The optimized interface significantly improved the dynamic detection range, with a low detection limit of 1.60 pM. This study not only provides a promising noninvasive diagnostic strategy for bladder cancer but also provides fundamental insights into the rational design of DNA nanostructure-based biosensing interfaces for high-performance electrochemical biosensors.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c02591","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:39:40Z","timestamp":1783478380000},"page":"26555-26564","source":"Crossref","is-referenced-by-count":0,"title":["An Interface-Regulated\nElectrochemical Biosensing\nPlatform Based on the Cascade Amplification of Primer Exchange Reaction\nand CRISPR\/Cas12a for Noninvasive Bladder Cancer Diagnosis"],"prefix":"10.1021","volume":"98","author":[{"given":"Linying","family":"Yu","sequence":"first","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310027"]},{"name":"Binjiang Institute of Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3791-6605","authenticated-orcid":true,"given":"Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310027"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Cai","sequence":"additional","affiliation":[{"name":"Binjiang Institute of Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunbo","family":"Gai","sequence":"additional","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310027"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Binjiang Institute of Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Fang","sequence":"additional","affiliation":[{"name":"Hangzhou Dianzi University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310018"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilei","family":"Ma","sequence":"additional","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-3733","authenticated-orcid":true,"given":"Xuesong","family":"Ye","sequence":"additional","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310027"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-2296","authenticated-orcid":true,"given":"Bo","family":"Liang","sequence":"additional","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310027"]},{"name":"Binjiang Institute of Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, P.R. China, 310053"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"2026091511090779600_cit1","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00194-23","article-title":"Review of\nBCG immunotherapy for bladder cancer","volume":"38","author":"Liatsos","year":"2025","journal-title":"Clin.\nMicrobiol. 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Sci."},{"key":"2026091511090779600_cit5","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics\n2018: GLOBOCAN estimates of incidence and\nmortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"Ca-Cancer J. Clin."},{"key":"2026091511090779600_cit6","doi-asserted-by":"publisher","first-page":"4038","DOI":"10.7150\/jca.28989","article-title":"A review on the\naccuracy of bladder cancer detection methods","volume":"10","author":"Zhu","year":"2019","journal-title":"J. Cancer"},{"key":"2026091511090779600_cit7","doi-asserted-by":"publisher","first-page":"2203224","DOI":"10.1002\/adma.202203224","article-title":"Integrated Urinalysis Devices Based on Interface-Engineered\nField-Effect Transistor Biosensors Incorporated With Electronic Circuits","volume":"34","author":"Yang","year":"2022","journal-title":"Adv. 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Electroanal.\nChem."},{"key":"2026091511090779600_cit36","doi-asserted-by":"publisher","first-page":"6827","DOI":"10.1021\/la700328r","article-title":"Effect\nof Molecular Crowding on the Response of an Electrochemical DNA Sensor","volume":"23","author":"Ricci","year":"2007","journal-title":"Langmuir"}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c02591","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/26555\/65813628\/acs.analchem.6c02591.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/26555\/65813628\/acs.analchem.6c02591.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:53:51Z","timestamp":1789487631000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/36\/26555\/5202663\/An-Interface-Regulated-Electrochemical-Biosensing"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":36,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,7,7]]},"published-print":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c02591","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]}}}