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However, CRISPR-Cas systems, despite their unparalleled nucleic acid detection performance, face inherent bottlenecks in protein sensing, including inefficient signal transduction, high background noise, and insufficient anti-interference capability in complex biological matrices. Herein, we report a modular fluorescence signal transduction platform integrating aptamer-functionalized magnetic beads, lanthanide metal\u2013organic frameworks (Ln-MOFs) with high nucleic acid affinity, and CRISPR-Cas12a\u2013mediated collateral cleavage amplification for sensitive cTnI detection. Target cTnI binding to magnetic bead-immobilized aptamers drives the formation of sandwich complexes with CRISPR activator DNA (act)\u2013functionalized Ln-MOFs, triggering phosphate-mediated release of act. The liberated act initiates robust Cas12a trans-cleavage activity, generating an amplified fluorescence readout. This platform achieves a limit of detection (LOD) of 0.1 pg mL\u20131 in serum samples, with excellent specificity against off-target interfering proteins. Validation in 28 clinical serum samples demonstrates near-perfect agreement with standard clinical ELISA measurements and yields an area under the curve (AUC) of 0.995, confirming its clinical diagnostic accuracy. Furthermore, the modular design enables facile reconfiguration for diverse protein biomarkers via aptamer substitution, providing a universal strategy to expand CRISPR-Cas systems toward non-nucleic acid target detection.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c01959","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T08:02:12Z","timestamp":1787126532000},"page":"24865-24875","source":"Crossref","is-referenced-by-count":0,"title":["Lanthanide\nMetal\u2013Organic Frameworks Enable\nTarget-Triggered CRISPR-Cas12a Activator Release for Ultrasensitive\nNon-nucleic Acid Biomarker Detection"],"prefix":"10.1021","volume":"98","author":[{"given":"Yongzhen","family":"Liu","sequence":"first","affiliation":[{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]},{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6170-6686","authenticated-orcid":true,"given":"Long","family":"Yu","sequence":"additional","affiliation":[{"name":"Zhongnan Hospital of Wuhan University , , Hubei Provincial Clinical Research Center for Molecular Diagnostics, ,","place":["Wuhan, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjin","family":"Shen","sequence":"additional","affiliation":[{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]},{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Gan","sequence":"additional","affiliation":[{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]},{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Tong","sequence":"additional","affiliation":[{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]},{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9125-1184","authenticated-orcid":true,"given":"Yuxiu","family":"Xiao","sequence":"additional","affiliation":[{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]},{"name":"Wuhan University , , ,","place":["Wuhan, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"2026090306461830300_cit1","doi-asserted-by":"publisher","first-page":"5603","DOI":"10.1038\/s41467-024-49810-z","article-title":"Barbed Arrow-Like Structure Membrane\nwith Ultra-High Rectification Coefficient Enables Ultra-Fast, Highly-Sensitive\nLateral-Flow Assay of cTnI","volume":"15","author":"Li","year":"2024","journal-title":"Nat. Commun."},{"key":"2026090306461830300_cit2","doi-asserted-by":"publisher","first-page":"e153","DOI":"10.1161\/cir.0000000000001052","article-title":"Heart Disease and Stroke Statistics\u25002022\nUpdate: A Report from the American Heart Association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation"},{"key":"2026090306461830300_cit3","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1016\/j.jacc.2018.08.1038","article-title":"Fourth\nUniversal Definition of Myocardial\nInfarction (2018)","volume":"72","author":"Thygesen","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026090306461830300_cit4","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.mayocp.2019.05.001","article-title":"Acute Myocardial\nInfarction in Young\nIndividuals","volume":"95","author":"Gulati","year":"2020","journal-title":"Mayo Clin. 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A Marker with High Specificity for Cardiac Injury","volume":"88","author":"Adams","year":"1993","journal-title":"Circulation"},{"key":"2026090306461830300_cit9","doi-asserted-by":"publisher","first-page":"135388","DOI":"10.1016\/j.snb.2024.135388","article-title":"Cu2+-Triggered Wavelength-Tunable\nReal-Time in Situ Fluorogenic Immunoassay\nfor Detection of cTnI in Human Serum","volume":"406","author":"Yang","year":"2024","journal-title":"Sens.\nActuators, B"},{"key":"2026090306461830300_cit10","doi-asserted-by":"publisher","first-page":"115508","DOI":"10.1016\/j.bios.2023.115508","article-title":"One-Pot Synthesis of\nAuPt@FexOy Nanoparticles with Excellent Peroxidase-Like Activity for\nDevelopment of Ultrasensitive Colorimetric Lateral Flow Immunoassay\nof Cardiac Troponin I","volume":"237","author":"Wang","year":"2023","journal-title":"Biosens. Bioelectron."},{"key":"2026090306461830300_cit11","doi-asserted-by":"publisher","first-page":"3593","DOI":"10.1021\/acsnano.0c10035","article-title":"Ultrasensitive and Highly Specific Lateral Flow Assays\nfor Point-of-Care Diagnosis","volume":"15","author":"Liu","year":"2021","journal-title":"ACS Nano"},{"key":"2026090306461830300_cit12","doi-asserted-by":"publisher","first-page":"114218","DOI":"10.1016\/j.bios.2022.114218","article-title":"Strategic Synthesis of Trimetallic Au@Ag\u2013Pt\nNanorattles for Ultrasensitive Colorimetric Detection in Lateral Flow\nImmunoassay","volume":"208","author":"Bai","year":"2022","journal-title":"Biosens. Bioelectron."},{"key":"2026090306461830300_cit13","doi-asserted-by":"publisher","first-page":"112015","DOI":"10.1016\/j.bios.2020.112015","article-title":"Recent Advances\nin\nHigh-Sensitivity Detection Methods for Paper-Based Lateral-Flow Assay","volume":"152","author":"Nguyen","year":"2020","journal-title":"Biosens. 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Mater. Interfaces"},{"key":"2026090306461830300_cit18","doi-asserted-by":"publisher","first-page":"2300656","DOI":"10.1002\/advs.202300656","article-title":"Repurposing\nCRISPR\/Cas to Discover SARS-CoV-2 Detecting and Neutralizing Aptamers","volume":"10","author":"Zhang","year":"2023","journal-title":"Adv. Sci."},{"key":"2026090306461830300_cit19","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1038\/s41587-020-0561-9","article-title":"Genome\nEditing with CRISPR-Cas Nucleases,\nBase Editors, Transposases and Prime","volume":"38","author":"Anzalone","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"2026090306461830300_cit20","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.molcel.2021.12.002","article-title":"The CRISPR-Cas Toolbox and Gene Editing\nTechnologies","volume":"82","author":"Liu","year":"2022","journal-title":"Mol. 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Soc."},{"key":"2026090306461830300_cit23","doi-asserted-by":"publisher","first-page":"118251","DOI":"10.1016\/j.trac.2025.118251","article-title":"Recent Application of CRISPR\/Cas in Plant Disease Detection","volume":"189","author":"Gong","year":"2025","journal-title":"TrAC, Trends Anal. Chem."},{"key":"2026090306461830300_cit24","doi-asserted-by":"publisher","first-page":"6559","DOI":"10.1038\/s41467-025-61742-w","article-title":"Efficient,\nCell-Type-Specific Production of Flavonols\nby Multiplexed CRISPR Activation of a Suite of Metabolic Enzymes","volume":"16","author":"Houbaert","year":"2025","journal-title":"Nat. Commun."},{"key":"2026090306461830300_cit25","doi-asserted-by":"publisher","first-page":"104349","DOI":"10.1016\/j.tifs.2024.104349","article-title":"Detection and Absolute Quantification\nBiosensing Tools for Food Authentication: CRISPR\/Cas, Digital CRISPR\nand Beyond","volume":"145","author":"Wu","year":"2024","journal-title":"Trends Food Sci. Technol."},{"key":"2026090306461830300_cit26","doi-asserted-by":"publisher","first-page":"58405","DOI":"10.1021\/acsami.4c14027","article-title":"Ce-MOF@Au-Based Electrochemical Immunosensor for Apolipoprotein A1\nDetection Using Nanobody Technology","volume":"16","author":"Sun","year":"2024","journal-title":"ACS Appl.\nMater. Interfaces"},{"key":"2026090306461830300_cit27","doi-asserted-by":"publisher","first-page":"1230444","DOI":"10.1126\/science.1230444","article-title":"The Chemistry and\nApplications of Metal-Organic Frameworks","volume":"341","author":"Furukawa","year":"2013","journal-title":"Science"},{"key":"2026090306461830300_cit28","doi-asserted-by":"publisher","first-page":"4484","DOI":"10.1039\/D0CS00955E","article-title":"Metal\u2013Organic\nFrameworks as Photoluminescent Biosensing Platforms: Mechanisms and\nApplications","volume":"50","author":"Zhao","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"2026090306461830300_cit29","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1021\/acs.analchem.1c04368","article-title":"Electrochemiluminescence Resonance\nEnergy Transfer System Based on Silver Metal\u2013Organic Frameworks\nas a Double-Amplified Emitter for Sensitive Detection of miRNA-107","volume":"94","author":"Xiao","year":"2022","journal-title":"Anal. Chem."},{"key":"2026090306461830300_cit30","doi-asserted-by":"publisher","first-page":"216102","DOI":"10.1016\/j.ccr.2024.216102","article-title":"Metal-Organic\nFrameworks (MOFs) and MOF Composites Based Biosensors","volume":"519","author":"Mohanty","year":"2024","journal-title":"Coord. Chem. Rev."},{"key":"2026090306461830300_cit31","doi-asserted-by":"publisher","first-page":"11455","DOI":"10.1021\/acs.analchem.4c01839","article-title":"Programmable\nLanthanide Metal\u2013Organic Framework for Ultra-Efficient Nucleic\nAcids Extraction and Interaction Analysis","volume":"96","author":"Yu","year":"2024","journal-title":"Anal.\nChem."},{"key":"2026090306461830300_cit32","doi-asserted-by":"publisher","first-page":"214707","DOI":"10.1016\/j.ccr.2022.214707","article-title":"Luminescent\nLanthanide Metal Organic\nFrameworks (Ln-MOFs): A Versatile Platform towards Organomolecule\nSensing","volume":"470","author":"Sahoo","year":"2022","journal-title":"Coord. Chem. Rev."},{"key":"2026090306461830300_cit33","doi-asserted-by":"publisher","first-page":"13730","DOI":"10.1021\/jacs.3c02019","article-title":"Biomimetic Photodegradation\nof Glyphosate in Carborane-Functionalized Nanoconfined Spaces","volume":"145","author":"Gan","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"2026090306461830300_cit34","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41586-021-04243-2","article-title":"Enantiomer-Dependent\nImmunological Response to Chiral\nNanoparticles","volume":"601","author":"Xu","year":"2022","journal-title":"Nature"},{"key":"2026090306461830300_cit35","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ccr.2019.02.020","article-title":"Nucleotide and DNA Coordinated Lanthanides: From Fundamentals to\nApplications","volume":"387","author":"He","year":"2019","journal-title":"Coordi. Chem. 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Mater. Interfaces"},{"key":"2026090306461830300_cit40","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1021\/acssensors.9b01759","article-title":"DNA Amplifier-Functionalized Metal-Organic\nFrameworks for Multiplexed Detection and Imaging of Intracellular\nmRNA","volume":"5","author":"Meng","year":"2020","journal-title":"ACS Sens."},{"key":"2026090306461830300_cit41","doi-asserted-by":"publisher","first-page":"15784","DOI":"10.1021\/jacs.7b07895","article-title":"Organelle-Specific\nTriggered Release of Immunostimulatory Oligonucleotides from Intrinsically\nCoordinated DNA\u2013Metal-Organic Frameworks with Soluble Exoskeleton","volume":"139","author":"Wang","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"2026090306461830300_cit42","doi-asserted-by":"publisher","first-page":"21267","DOI":"10.1021\/jacs.0c10442","article-title":"Construction\nof Molecular Sensing and Logic Systems Based on Site-Occupying Effect-Modulated\nMOF\u2013DNA Interaction","volume":"142","author":"Yu","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"2026090306461830300_cit43","doi-asserted-by":"publisher","first-page":"114382","DOI":"10.1016\/j.bios.2022.114382","article-title":"A Programmable and Sensitive CRISPR\/Cas12a\u2013Based\nMicroRNA\nDetection Platform Combined with Hybridization Chain Reaction","volume":"211","author":"Jia","year":"2022","journal-title":"Biosens. Bioelectron."},{"key":"2026090306461830300_cit44","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1126\/science.aar6245","article-title":"CRISPR-Cas12a\nTarget Binding Unleashes\nIndiscriminate Single-Stranded DNase Activity","volume":"360","author":"Chen","year":"2018","journal-title":"Science"},{"key":"2026090306461830300_cit45","doi-asserted-by":"publisher","first-page":"7942","DOI":"10.1021\/acs.analchem.1c00686","article-title":"CRISPR\/Cas12a\u2013Assisted\nLigation-Initiated Loop-Mediated Isothermal Amplification (CAL-LAMP)\nfor Highly Specific Detection of microRNAs","volume":"93","author":"Zhang","year":"2021","journal-title":"Anal. Chem."},{"key":"2026090306461830300_cit46","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202504246","article-title":"Dual-Enhanced\nLanthanide MOF\u2013Based Fluorescent\nBio-Barcode via Conformational Regulation for Ultrasensitive Detection\nof DNA Epigenetic Biomarker","volume":"21","author":"Feng","year":"2025","journal-title":"Small"},{"key":"2026090306461830300_cit47","doi-asserted-by":"publisher","first-page":"2300547","DOI":"10.1002\/smll.202300547","article-title":"Thermodynamically and Kinetically Stabilized Pt Clusters Against\nSintering on CeO2 Nanofibers Through Enclosing CeO2 Nanocubes","volume":"19","author":"Wang","year":"2023","journal-title":"Small"}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c01959","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/34\/24865\/66856545\/acs.analchem.6c01959.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/34\/24865\/66856545\/acs.analchem.6c01959.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:46:24Z","timestamp":1788432384000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/34\/24865\/5275871\/Lanthanide-Metal-Organic-Frameworks-Enable-Target"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":47,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2026,8,19]]},"published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c01959","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}