Detection of Amyloid β Oligomers by a Fluorescence Ratio Strategy Based on Optically Trapped Highly Doped Upconversion Nanoparticles-SiO₂@Metal–Organic Framework Microspheres

Abstract

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-SiO 2 @ 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 UCL 540 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.

Combining Upconversion Luminescence, Photothermy, and Electrochemistry for Highly Accurate Triple-Signal Detection of Hydrogen Sulfide by Optically Trapping Single Microbeads

“…Optical tweezers, which capture objects using a focused laser beam, can generate a high energy density optical trap (10 6 –10 7 W·cm –2 ) under low-power excitation (0.5 W·cm –2 ). , In line with this, H-UCNPs can be excited by optical tweezers to produce strong luminescence, which enhances the detection sensitivity for luminescent and photothermal detection. Moreover, the high-intensity excitation light source does not produce an excessive thermal effect under optical trapping, making it useful for biological sample testing …”

Recent developments in the chemical biology of amyloid-β oligomer targeting

“…5B). 109 This nanoprobe was constructed by packing the metal-organic framework ZIF-8 on the surface of upconversion nanoparticles. The black hole quencher (BHQ-1) wrapped in ZIF-8 can quench the luminescence of H-USM/BHQ-1 at 540 nm (UCL 540 ) without affecting the emission at 654 nm (UCL 654 ).…”

Heterostructures Combining Upconversion Nanoparticles and Metal–Organic Framework: Fundamental, Classification, and Theranostic Applications

“…The chemical nature and the porosity of MOFs can provide a variety of ways, such as physical adsorption, electrostatic attraction, DNA temptation, and chemical coordination, to anchor analyte of distinct types to the surface, rendering UCNPs@MOFs heterostructure as a robust and universal nanoplatform for high-sensitivity biosensing. [53] DNA temptation has been used in UCNPs@MOFs heterostructure for specific detection of bisphenol A (BPA) in high-salt foods, [43] which combined aptamer modified UCNPs (DNA1-UCNPs) and complementary DNA-modified metal organic frameworks (DNA2-MOFs). DNA pair hybridization brought UCNPs and MOFs in close contact and resulted in ≈90% UCL quenching efficiency, due to the strong spectral overlap between MOF absorption (500-700 nm) and UCNPs emission (540/650 nm).…”