Multiple-Signal Amplification Strategy to Fabricate an Ultrasensitive Electrochemiluminescence Magnetic Immunosensor for Detecting Biomarkers of Alzheimer’s Disease via Iridium-Based Self-Enhancing Nanoemitters

Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive decline, significantly impairing the daily life of elderly individuals. The low abundance of blood-based biomarkers in AD necessitates higher analytical technique requirements. Herein, one novel iridium-based ECL self-enhanced nanoemitter (TPrA@Ir-SiO₂) was unprecedentedly reported, and it was further used to construct an ultrasensitive ECL magnetic immunosensor by a multiple-signal amplification strategy to unequally sensitively and accurately detect the AD blood-based biomarker (P-tau181) in this work. The initial signal amplification was accomplished via incorporating a new efficient iridium-based luminophore named Ir(mdq)₂(acac) and a corresponding coreactant into silica nanoparticles to successfully obtain TPrA@Ir-SiO₂. In addition, the specific and high-affinity interactions between streptavidin and biotin were subsequently employed to further facilitate signal amplification. Based on the advantages of the luminophore itself and the high-affinity interactions between biotin and streptavidin, the corresponding ECL immunosensor proposed in this work exhibited remarkable sensitivity, covering a wide linear range from 0.1 pg/mL to 0.1 μg/mL, and achieved an ultralow limit of detection of 68.58 fg/mL (S/N = 3), and it also exhibited outstanding recovery (98-104%) and RSD (1.92-4.86%) in the detection of serum samples by the spiking method. These remarkable results undoubtedly demonstrate the potential of self-enhanced ECL nanoemitters combined with a synergistic signal amplification strategy bearing streptavidin-biotin in detecting AD blood-based biomarkers, providing accurate and reliable solutions for early diagnosis and monitoring of AD, which would open a new avenue to effectively reduce the burden on AD patients' families and society in the future.