QR-code‑linked additive-engineered aptasensor for non-invasive impedimetric biosensing of neurodegenerative biomarker Aβ-42 with computational modelling validation for high selectivity

The accumulation of plaques of amyloid and neurofibrillary tangles in the brain is a hallmark of Alzheimer’s disease (AD), which causes severe cognitive and functional deficits. Early detection is essential for effective treatment. A key biomarker for AD is amyloid beta oligomers (AβO), particularly Aβ42, which poses a significant challenge in accurate identification. Non-invasive wearable devices facilitate early detection. This enables timely prevention, lifestyle adjustment and effective treatment. This work demonstrates a proof-of-concept wearable aptasensor platform under controlled laboratory conditions and introduces a QR code-linked, mouthguard-integrated paper analytical device (MIPAD) for non-invasive detection of Aβ42 using impedimetric biosensing. The wearable prototype device features a paper-based electrode enhanced with silver nanoparticles, which amplify detection signals and improve specificity. A highly selective aptamer targeting Aβ42 was employed to facilitate selective recognition of oligomeric amyloid, which has been confirmed through docking. Its specificity was confirmed through molecular docking of the aptamer–peptide interaction, and further validated via electrophoretic mobility shift assay (EMSA) to ensure optimised sensor performance. The platform integrates a QR code system that provides users with step-by-step operational instructions. Experimental results demonstrated the MIPAD’s ability to electrochemically detect Aβ42 at concentrations ranging from 0.1 ng/mL to 10 µg/mL, with an LOD of 2.26 ng/mL.