Metal Ion-Based Chemical Coordination Amplification: A Chromophore In Situ Deposition Strategy for Visual Sensitivity-Enhanced Lateral Flow Immunochromatography Assays

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 Zr⁴⁺ 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 (<i>R</i>² = 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.