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However, the intrinsically low abundance and rapid clearance of ctDNA pose substantial challenges for conventional analytical techniques, such as droplet digital PCR and next\u2010generation sequencing. Here, we introduce a label\u2010free dual\u2010channel synergistic detection strategy that enables quantitative analysis of ctDNA at the zeptomolar level. Leveraging a synergistic design that includes structural symmetry breaking and momentum condition regulation, the optical platform overcomes the inherent structural field confinement and enhances the effectiveness of target\u2010contacted sensing. By integrating a DNA tetrahedron\u2010hybridization chain reaction\u2010gold nanoparticle cascade amplification system, the dual\u2010channel synergistic biosensor achieves an ultra\u2010low detection limit of 74\n                    <jats:sc>zM<\/jats:sc>\n                    while covering a dynamic range spanning 12 orders of magnitude. Clinical validation has confirmed that this dual\u2010channel synergistic detection strategy can accurately identify the IDH1.R132H mutation in glioma patients with as little as 1\u00a0\u00b5L of sample, and deliver crucial clinical information such as tumor size and staging. This label\u2010free, rapid, cost\u2010effective, and highly sensitive biosensing platform offers a powerful tool for early cancer screening, molecular diagnostics, and longitudinal disease monitoring.\n                  <\/jats:p>","DOI":"10.1002\/advs.75443","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T15:21:38Z","timestamp":1777303298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Dual\u2010Channel Synergistic Ultrasensitive Biosensor for Tumor Liquid Biopsy"],"prefix":"10.1002","volume":"13","author":[{"given":"Yu","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Peking University Third Hospital  Beijing P. R. China"},{"name":"Department of Intensive Care Unit Peking University Third Hospital  Beijing P. R. 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