Fe3O4@MoS2@Au-Ag microsphere-based ultrasensitive immunobiosensor for the early diagnosis of Alzheimer's disease.

Alzheimer's Disease (AD), a most common neurodegenerative disease, has aroused people's great attention. Amyloid-β 1-42 (Aβ42) from serum/plasma has been listed as Core 1 biomarker in diagnostic guide and explore an ultrasensitive detection method of Aβ42 is of great significance for early AD diagnosis and treatment. Herein, an ultrasensitive fluorescent biosensor for Aβ42 detection is designed, which is composed of Fe3O4@MoS2 microsphere and Au-Ag alloy. Compared with typical single gold nanoparticles in traditional fluorescent biosensor, alloy nanoparticles can generate a stronger electromagnetic field to enhance the fluorescence of quantum dots via surface plasmon resonance, achieve the effect of signal amplification. Importantly, our design significantly improved the limit of detection to 11 ag/mL, with a linear response ranging from 0.1 to 104 fg/mL. Moreover, by replacing the detection antibody in the biosensor, it can also be applied to other common AD biomarkers, such as Aβ40 (linear range: 0.1 to 105 fg/mL, LOD: 61 ag/mL) and total Tau protein (linear range: 0.1 to 105 fg/mL, LOD: 40 ag/mL). The biosensor exhibited excellent performance in both spiked and real serum samples. This fluorescent biosensor based on Au-Ag alloy strategy with ultra-sensitivity and good selectivity, provides a reliable solution for AD's early diagnosis.