Song Jiaren, Xu Changdi, Zeng Siqi, Zuo Wanchao, Yang Qing, Hu Qiannan, Meng Xiangming, Ye Jinjun, Dai Jianjun, Ju Yanmin
State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China.
Anal Chem. 2025 Feb 18;97(6):3477-3485. doi: 10.1021/acs.analchem.4c05781. Epub 2025 Feb 4.
Traditional lateral flow immunochromatography assays (LFIAs) have faced low sensitivity for trace detection due to the lack of colorimetric brightness. The current strategies to improve sensitivity commonly have the disadvantages of an uncontrollable enhancement process or high background interference, leading to huge obstacles for signal readout. Herein, an in situ metal ion-based chemical coordination amplification (MICCA) strategy has been reported. Metal ion clusters on metal-organic frameworks could coordinate with chromophores to produce colored complexes for visual signal enhancement. A Zr-based metal AIEgen framework (MAF) loaded with Prussian blue was chosen as the dual-mode signal tag for colorimetric and fluorescent readout. MAF could be employed as a grafting substrate to in situ deposit chromophores through the coordination with Zr clusters and arsenazo III. The process of MICCA was in situ, controllable, and free of background interference. For target cancer biomarker alpha-fetoprotein (AFP), the limit of detection (LOD) by the naked eye was 25 ng/mL, and the LODs of MICCA and fluorescence were 5 ng/mL, which was 5-fold decreased. Significantly, MICCA-LFIA could effectively differentiate between AFP-positive and AFP-negative clinical serum samples. The quantitative results were highly consistent with clinical results ( = 0.9927). This work explored the application of metal ion-based chemical coordination reactions in signal amplification strategies and provided ideas for high-sensitivity LFIA development.
传统的侧向流动免疫色谱分析（LFIA）由于缺乏比色亮度，在痕量检测方面灵敏度较低。目前提高灵敏度的策略通常存在增强过程不可控或背景干扰高的缺点，给信号读出带来巨大障碍。在此，报道了一种基于原位金属离子的化学配位放大（MICCA）策略。金属有机框架上的金属离子簇可与发色团配位，生成有色络合物以增强视觉信号。选择负载普鲁士蓝的锆基金属聚集诱导发光框架（MAF）作为比色和荧光读出的双模信号标签。MAF可作为接枝底物，通过与锆簇和偶氮胂III配位原位沉积发色团。MICCA过程是原位的、可控的且无背景干扰。对于目标癌症生物标志物甲胎蛋白（AFP），肉眼检测限（LOD）为25 ng/mL，MICCA和荧光的LOD均为5 ng/mL，降低了5倍。值得注意的是，MICCA-LFIA能够有效区分AFP阳性和AFP阴性临床血清样本。定量结果与临床结果高度一致（=0.9927）。这项工作探索了基于金属离子的化学配位反应在信号放大策略中的应用，并为高灵敏度LFIA的发展提供了思路。
