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Here, we report a conceptually novel reaction termed \u201cradical\u2010mediated in situ fluorescence dye deposition\u201d (RIFD) as a simple interfacial signal amplification strategy to overcome the limitation. This first discovered RIFD follows a universal \u201cthree\u2010element principle\u201d, where the coexistence of beads, free radicals, and dyes suffices for fluorescence labeling, eliminating the pre\u2010conjugation of dyes to detection probes required in traditional methods. Mechanistic studies reveal that this radical\u2010triggered RIFD possibly follows three distinct pathways, including amide condensation on lysine residues, covalent biphenyl formation on tyrosine residues, or radical\u2010dye co\u2010deposition. It facilitates local and ultrafast (within 5 min) dye\u2010trapping specifically on target\u2010positive barcode beads. Consequently, the established RIFD\u2010based immunoassay achieves a limit of detection of 12 fg\/mL for IL\u201010, a 100\u2010fold improvement over the conventional suspension chip method, and also successfully differentiates Alzheimer's disease patients from healthy controls by quantifying low\u2010abundance plasma p\u2010Tau217. Multiplexed detection is further validated with a three\u2010plex cytokines panel. Our reported RIFD represents a powerful in situ fluorescence labeling tool, advancing protein biomarker detection toward the sub\u2010pg\/mL level with broad implications for clinical diagnostics.<\/jats:p>","DOI":"10.1002\/advs.76670","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:40:48Z","timestamp":1784551248000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Radical\u2010Mediated In Situ Fluorescence Dye Deposition: A Simple Interfacial Signal Amplification Reaction for Ultrasensitive Immunoassay on Barcode Beads"],"prefix":"10.1002","volume":"13","author":[{"given":"Jiayu","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Shanghai Jiao Tong University  Shanghai 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