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

Zhe Ren, Wenjuan Guo, Shuqian Sun, Xin Liu, Zelong Fan, Fangfang Wang, Ahmed A. Ibrahim, Ahmad Umar, Abdulrab Ahmed M. Alkhanjaf, S. Baskoutas

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-NH2 as a carrier container to load MB (Methylene Blue), and Fe3O4 MNPs (iron oxide magnetic nanoparticles) with aptamer (ssDNA-Fe3O4 MNPs) fixed on their surface for biological gating. The ssDNA-Fe3O4 MNPs were immobilized onto the surface of UIO-66-NH2 through hydrogen bonding between the aptamer and the -NH2 group on the surface of UIO-66-NH2, thereby encapsulating MB and forming ssDNA-Fe3O4@MB@UIO-66-NH2. During the detection of AβO, the aptamer selectively reacted with AβO to form the AβO-ssDNA-Fe3O4 complex, leading to its detachment from the surface of UIO-66-NH2. This detachment facilitated the release of MB, enabling its electrochemical detection. Simultaneously, the AβO-ssDNA-Fe3O4 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 Fe3O4 MNPs. Consequently, the aptamer detached from the surface of Fe3O4 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.