Tetrahedral DNA-Linker stable Europium nanoparticles for ultrasensible time-resolved fluorescence lateral flow immunoassay

Accurate quantification of interleukin-6 (IL6), a biomarker central to sepsis and cytokine release syndrome, is essential for assessing disease severity. Here, we present a high-performance lateral flow assay (LFA) that leverages a novel conjugate: europium nanoparticles (EuNPs) labels linked via tetrahedral DNA frameworks (TDFs). The TDF precisely controls antibody orientation, minimizes nonspecific binding, and improves conjugate stability. Combined with the strong, time-resolved fluorescence of EuNPs, this design achieves a broad dynamic range and preserves linearity at high analyte concentrations. The platform quantitatively detects IL6 from 0 to 5000 pg/mL within 10 min, showing excellent agreement with reference methods. This DNA-nanostructure-enhanced approach provides a robust and portable point-of-care testing strategy for critical clinical decision-making. • A EuNP-Ab&TDF-based fluorescent lateral flow assay was developed for portable IL6 quantification. • TDF conjugation enhanced antibody stability and minimized nonspecific adsorption at high analyte concentrations. • Reliable linearity ( R 2 = 0.961) was achieved across 0–5000 pg/mL, covering clinically relevant IL6 ranges. • Rapid and sensitive detection was completed within 10 min, suitable for bedside and emergency monitoring.