Dual-Quenching Electrochemiluminescence Strategy Based on Three-Dimensional Metal-Organic Frameworks for Ultrasensitive Detection of Amyloid-β.

We have proposed a dual-quenching electrochemiluminescence (ECL) strategy which is based on tris(2,2'-bipyridyl)ruthenium(II) [Ru(bpy)32+] as chromophores caged in three-dimensional (3D) zinc oxalate metal-organic frameworks [Ru(bpy)32+/zinc oxalate MOFs] for ultrasensitive detection of amyloid-β (Aβ). The three-dimensional chromophore connectivity in zinc oxalate MOFs provided a network for rapid excited-state energy transfer migration among Ru(bpy)32+ units which shielded the chromophores from solvent molecules and led to a high-energy Ru emission efficiency. In addition, we found that both Au nanoparticles and NiFe-based nanocube MOFs could contribute to the reduction of the ECL intensity of the chromophore. The ECL emission spectra of 3D Ru(bpy)32+/zinc oxalate MOFs overlapped appropriately with the ultraviolet-visible (UV-vis) absorption spectra of Au@NiFe MOFs composites, which could trigger the resonance energy transfer (RET) behavior between Ru(bpy)32+/zinc oxalate MOFs (donor) and Au@NiFe MOFs (acceptor), achieving the dual-quenching effect of Ru(bpy)32+ encapsulated in 3D zinc oxalate MOFs and significantly boosting the sensitivity of the Aβ detection immunosensor. In order to examine the clinical practicability, we have applied it to verify the content of Aβ solution ranging from 100 fg mL-1 to 50 ng mL-1 and obtained the calibration curve with high correlation coefficient, along with the low limit of detection of 13.8 fg mL-1. Above all, this work demonstrated an approach of constructing dual-quenching effect ECL immunosensors in whole 3D MOF systems and its application in ECL detection methodology.