Detection of Amyloid β Oligomers by a Fluorescence Ratio Strategy Based on Optically Trapped Highly Doped...

Alzheimer's disease (AD), known as a progressive neurodegenerative disorder, has had a terrible impact on the health of aged people. Due to its severity, early diagnosis of AD is significant to retard the progress and provide timely treatment. Here, we report a fluorescence ratio detection of AD biomarker amyloid β oligomers (AβOs) by combining highly doped upconversion nanoparticles-SiO₂@metal-organic framework/black hole quencher (H-USM/BHQ-1) microspheres with optical tweezer (OT) microscopic imaging. Optical trapping a single microsphere not only avoids the interference of fluid viscosity but also provides a high power density laser source to efficiently stimulate upconversion luminescence (UCL) of highly doped upconversion nanoparticles (H-UCNPs). Under this condition, H-UCNPs show stronger UCL and greater power-dependent properties compared to low-doped ones. Moreover, the closely packed quenching molecules BHQ-1 on a metal-organic framework (ZIF-8) exhibit excellent quenching efficiency for upconversion 525 and 540 nm emission. Also, the luminescent resonance energy transfer efficiency reaches 89.58%. When different concentrations of AβOs are present, the UCL₅₄₀ recovers due to the decomposition of ZIF-8 and the release of BHQ-1. Using 540 and 654 nm emission ratio of highly doped UCNPs as reporters, the limit of detection reaches 28.4 pM for the quantitative determination of AβOs. Besides, this strategy is able to selectively quantify the AβO concentration. Therefore, we demonstrated the combination of optical trapping and highly doped UCNPs which is applied for the detection of AβOs with high sensitivity and specificity.