Cytokeratin 19 fragment (CYFRA21-1) is considered to be a potential marker for the diagnosis and of classification of lung cancer. It is highly desired to develop rapid and highly sensitive label-free chemiluminescence (CL) immunosensors for the detection of CYFRA21-1. In this work, magnetic core–shell nanocomposite Fe₃O₄@nickel–cobalt double hydroxide (Fe₃O₄@DH) was used for the first time as a carrier to synthesize N-(4-aminobutyl)-N-ethylisoluminol (ABEI) and gold and silver nanocluster (AuAgNC) bifunctionalized magnetic nanomaterials Fe₃O₄@DH/AuAgNCs-ABEI. The resulting Fe₃O₄@DH/AuAgNCs-ABEI demonstrated excellent CL performance, attributed to the exceptional catalytic capability of nickel–cobalt double hydroxide (NiCo-DH) and AuAgNCs, as well as the large specific surface area of NiCo-DH for AuAgNCs and ABEI enrichment. Moreover, Fe₃O₄@DH/AuAgNCs-ABEI exhibited superior stability compared to Fe₃O₄-based CL-functionalized magnetic nanomaterials, owing to the presence of NiCo-DH shells. On this basis, a label-free CL immunosensor using CYFRA21-1 antibody-modified Fe₃O₄@DH/AuAgNCs-ABEI as an analytical interface was constructed for the detection of CYFRA21-1 in the range from 1.0 × 10^–13 to 1.0 × 10^–8 g/mL. The detection limit of this CL immunosensor was 47.7 fg/mL, 4 orders of magnitude lower than existing CL methods. The CL immunosensor was able to accurately detect the concentration of CYFRA21-1 in serum samples, as evidenced by ELISA results. More importantly, it not only distinguished well between healthy persons and lung cancer patients (90.0% sensitivity and 90.0% specificity), but also effectively distinguished between patients with non-small cell lung cancer and small cell lung cancer (80.0% sensitivity and 86.7% specificity).

中文翻译：

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化学发光 Fe3O4@Nickel-钴双氢氧化物磁性核-壳纳米材料作为无标记 CYFRA21-1 免疫传感的分析界面


细胞角蛋白 19 片段 （CYFRA21-1） 被认为是肺癌诊断和分类的潜在标志物。非常需要开发快速、高灵敏度的无标记化学发光 （CL） 免疫传感器来检测 CYFRA21-1。在本工作中，磁性核壳纳米复合材料 Fe₃O₄@nickel-钴双氢氧化物 （Fe₃O₄@DH） 首次用作载体合成了 N-（4-氨基丁基）-N-乙基异鲁米醇 （ABEI） 和金银纳米团簇 （AuAgNC） 双功能化磁性纳米材料 Fe₃O₄@DH/AuAgNCs-ABEI。所得的 Fe₃O₄@DH/AuAgNCs-ABEI 表现出优异的 CL 性能，这归因于镍钴双氢氧化物 （NiCo-DH） 和 AuAgNCs 的出色催化能力，以及 NiCo-DH 对 AuAgNCs 和 ABEI 富集的大比表面积。此外，由于存在 NiCo-DH 壳层，与基于 Fe₃O₄ 的 CL 功能化磁性纳米材料相比，Fe₃O₄@DH/AuAgNCs-ABEI 表现出优异的稳定性。在此基础上，使用 CYFRA21-1 抗体修饰的 Fe₃O₄@DH/AuAgNCs-ABEI 作为分析界面构建了无标记 CL 免疫传感器，用于检测 1.0 × ^10-13 至 1.0 × ^10-8 g/mL 范围内的 CYFRA21-1。该 CL 免疫传感器的检测限为 47.7 fg/mL，比现有的 CL 方法低 4 个数量级。CL 免疫传感器能够准确检测血清样品中 CYFRA21-1 的浓度，ELISA 结果证明了这一点。更重要的是，它不仅很好地区分了健康人和肺癌患者 （90.0% 的敏感性和 90.0% 特异性），也有效区分非小细胞肺癌患者和小细胞肺癌患者 （80.0% 敏感性和 86.7% 特异性）。