Filter‐Assisted ICP‐MS Tumor Liquid Biopsy Enabled by Dual‐Target‐Regulated Functional DNA Nanospheres Cascade Amplification

作者：Yiman Wu, Yue Wang, Yan Li, Ke Huang, Kai Chang, Piaopiao Chen · 发表于：Small Methods · 年份：2025 · DOI：10.1002/smtd.202500314 · 被引用次数：9 · 研究领域：Advanced biosensing and bioanalysis techniques、Nanopore and Nanochannel Transport Studies、Biosensors and Analytical Detection

Abstract An ultrasensitive ICP‐MS aptasensor is developed utilizing a label‐free, simple filter membrane‐assisted separation technique combined with nucleic acid signal amplification for the analysis of circulating tumor cells (CTCs) in lung cancer clinical samples. The approach is based on the high‐affinity interaction between aptamers and PD‐L1 and mucin 1, which are overexpressed on the cell surface, in conjunction with functional Y‐DNA nanospheres and catalytic hairpin assembly amplifications, enabling the simultaneous detection of two proteins. Additionally, a four‐armed nanostructure with significant spatial site resistance is self‐assembled by introducing streptavidin with biotinylated‐hairpin structures, improving the separation efficiency of the filter membrane. This structural design enables the effective isolation of biotin‐T‐Hg 2+ ‐T and biotin‐C‐Ag + ‐C from free Hg 2+ and Ag + , facilitating highly sensitive dual‐protein detection via ICP‐MS. The limits of detection reached ag mL −1 levels for proteins and single‐cell levels for A549 cells. CTCs are extracted from whole blood samples of lung cancer patients within 45 min through a simple centrifugation procedure. Quantification of CTCs is performed in 37 clinical samples, demonstrating results consistent with clinical diagnoses. The assay exhibits a specificity of 100% and a sensitivity of 94.5%.