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Here, we report an S-Loop CRISPR dual-mode assay (SCDA) for perfluorooctanoic acid (PFOA). PFOA-induced aptamer displacement initiates an AMPLON-derived isothermal S-Loop reaction mediated by an eight-arm poly(ethylene glycol) spider-inspired primer (SP), and the resulting amplicons activate Cas12a trans-cleavage. A FAM\u2013quencher reporter provides the fluorescence (FL) output, whereas cleavage-induced removal of CdS from a CdS\/gold nanoparticle\/ZnIn2S4 photoelectrode releases an electron cage produced by type-I carrier confinement and visible-light shielding of the underlying photoactive layer, thereby restoring the photoelectrochemical (PEC) signal. At target concentrations of 10\u201313, 10\u201310, and 10\u20137 M, Cas12a reporter cleavage was linear with time over the first 10 min, and PEG20000-SP produced the largest amplification response and highest apparent reporter-signal rising rate. PEC and FL calibrations were linear over 10\u201315\u201310\u20137 and 10\u201314\u201310\u20137 M, respectively, with equations I = 12.3328 + 0.7207 log10C (R2 = 0.9929) and F = 13631.32 + 845.64 log10C (R2 = 0.9926). Estimated blank-based limits of detection were 1.27 \u00d7 10\u201316 M (PEC) and 8.34 \u00d7 10\u201316 M (FL); these estimates are below the lowest tested standards and do not establish quantitation below the calibration ranges. Paired results were compared within the common calibration range using log-concentration differences and relative percent differences. Consensus recoveries were 94.3\u2013103.6% in milk and 95.7\u2013103.0% in river water. SCDA therefore combines sensitive dual-readout with an explicit preliminary screen for discordant measurements.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c05089","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:01:34Z","timestamp":1789030894000},"page":"27701-27713","source":"Crossref","is-referenced-by-count":0,"title":["Spider-Inspired\nS-Loop Amplification Repurposes\nan Electron Cage for Photoelectrochemical\u2013Fluorescence Detection\nof Perfluorooctanoic Acid"],"prefix":"10.1021","volume":"98","author":[{"given":"Yiwei","family":"Zheng","sequence":"first","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Feng","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxia","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1342-8447","authenticated-orcid":true,"given":"Xuecai","family":"Tan","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9332-0497","authenticated-orcid":true,"given":"Kejing","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5437-0161","authenticated-orcid":true,"given":"Jiawen","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangxi Minzu University , , ,","place":["Nanning, China, 530006"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"issue":"6580","key":"2026092208072853700_cit1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg9065","article-title":"Per- and polyfluoroalkyl substances in the\nenvironment","volume":"375","author":"Evich","year":"2022","journal-title":"Science"},{"issue":"19","key":"2026092208072853700_cit2","doi-asserted-by":"publisher","first-page":"2420883","DOI":"10.1002\/adfm.202420883","article-title":"Recent Progress in\nAdvanced Catalytic\nStrategies for C\u2013F Bond Cleavage in Waste Refrigerants: A Review","volume":"35","author":"Wang","year":"2025","journal-title":"Adv. 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