Dual-mode transfer response based on electrochemical and fluorescence signals for the detection of amyloid-beta oligomers (AβO).

An aptamer sensor has been developed utilizing a dual-mode and stimuli-responsive strategy for quantitative detection of AβO (amyloid-beta oligomers) through simultaneous electrochemical and fluorescence detection. To achieve this, we employed UIO-66-NH as a carrier container to load MB (Methylene Blue), and FeO MNPs (iron oxide magnetic nanoparticles) with aptamer (ssDNA-FeO MNPs) fixed on their surface for biological gating. The ssDNA-FeO MNPs were immobilized onto the surface of UIO-66-NH through hydrogen bonding between the aptamer and the -NH group on the surface of UIO-66-NH, thereby encapsulating MB and forming ssDNA-FeO@MB@UIO-66-NH. During the detection of AβO, the aptamer selectively reacted with AβO to form the AβO-ssDNA-FeO complex, leading to its detachment from the surface of UIO-66-NH. This detachment facilitated the release of MB, enabling its electrochemical detection. Simultaneously, the AβO-ssDNA-FeO complex was efficiently collected and separated using a magnet after leaving the container's surface. Furthermore, the addition of NaOH facilitated the disconnection of biotin modifications at the 3' end of the aptamer from the avidin modifications on the FeO MNPs. Consequently, the aptamer detached from the surface of FeO MNPs, resulting in the restoration of fluorescence intensity of FAM (fluorescein-5'-carboxamidite) modified at its 5' end for fluorescence detection. The dual-mode sensor exhibited significantly enhanced differential pulse voltammetry signals and fluorescence intensity compared to those in the absence of AβO. The sensor demonstrated a wide detection range of 10 fM to 10 μM, with a detection limit of 3.4 fM. It displayed excellent performance in detecting actual samples and holds promising prospects for early diagnosis of Alzheimer's disease.