Smartphone-Assisted Upconversion Nanoparticle Sensing Platform for Noninvasive Early Diagnosis of Alzheimer’s Disease

Alzheimer’s disease (AD), a progressive and irreversible neurodegenerative disorder, is a growing global health concern. Early-stage detection of AD is challenging, typically requiring costly imaging techniques or invasive biochemical analyses performed by professionally trained medical staff. This study presents an approach that employs upconversion nanoparticles (UCNPs) as biosensors, integrated with smartphone cameras as detection devices, in place of traditional complex and costly luminescence spectroscopy, to enable noninvasive, highly sensitive, and rapid detection of the key AD biomarker, β-amyloid 42 (Aβ 42 ). In this study, UCNPs were modified by poly(acrylic acid) (PAA), ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride (EDC), and N -hydroxysuccinimide (NHS) to immobilize Aβ 42 antibodies. After antibody–antigen binding, the nonradiative energy transfer will induce a reduction in luminescence intensity, establishing a calibration curve for Aβ 42 detection. This approach demonstrated a strong linear correlation between UCNP luminescence intensity and Aβ 42 concentration, achieving an R 2 value of 0.967 using conventional luminescence spectroscopy. By converting smartphone-captured luminescence images to grayscale, a portable, low-cost UCNP-based biosensor yielded an R 2 value of 0.953, underscoring its potential for noninvasive, cost-effective early AD detection with performance rivaling that of traditional laboratory instruments.