Ultrasensitive portable aptamer-electrochemical sensor for point-of-care testing of Alzheimer's biomarker amyloid-β oligomers

Early and accessible diagnosis of Alzheimer's disease (AD) is crucial for effective intervention, yet current methods like amyloid-PET(positron emission tomography) imaging remain cost-prohibitive and lack scalability. Here, we present a miniaturized electrochemical platform for ultrasensitive detection of amyloid-β oligomers (AβOs), pathogenic biomarkers implicated in early AD progression. The system employs a disposable screen-printed electrode functionalized with gold nanoparticles (AuNPs) and thiolated aptamers, leveraging Au S bonds for oriented aptamer immobilization and AβO-specific recognition. This aptasensor achieves a linear detection range of 10 pg/mL to 100 μg/mL (R 2  = 0.995) with a limit of detection (LOD) of 2.3 pg/mL (S/N = 3) in human serum, coupled with robust recovery rates (94.9–108.89 %) and low inter-assay variability (RSD < 5.5 %). Integrated with a handheld analyzer (90 × 50 × 8 mm, 30 g) executing differential pulse voltammetry (DPV), the platform wirelessly transmits data to a smartphone app, delivering quantitative results within 20 s at <$1 per test. Preclinical validation using blood from mice injected with AβO protein showed that the platform's test results were highly correlated with the injected dose (R 2  = 0.995, p  < 0.001) and outperformed ELISA in terms of efficiency and cost. By combining laboratory-grade performance, portability, and scalability, the system addresses unmet needs in community-based AD screening and has scalable potential for monitoring neurodegenerative proteomics.