Microarray chip based on surface-enhanced raman scattering-chiral anisotropy for ultrasensitive detection of Aβ42 as an Alzheimer’s disease-associated serum biomarker

In this study, a highly sensitive surface-enhanced Raman scattering-chiral anisotropy (SERS-ChA)-based microarray chip was fabricated for the quantitative analysis of β-amyloid protein (Aβ42) in Alzheimer’s disease (AD). To construct the chip, D-type chiral gold nanoparticles (CG NPs) were employed as the plasmonic substrate, creating uniformly distributed and densely packed hotspots. The localized chiral plasmonic electromagnetic fields generated at the chiral hotspots provide a chirality-dependent enhancement preference for Aβ42 molecules, leading to significant enhancement of their characteristic Raman signals and thereby improving the sensitivity and specificity of detection. Within the linear range of 100 fg/mL to 10 ng/mL, the logarithmic concentration of Aβ42 showed a strong linear correlation with the SERS signal intensity at 1322 cm − 1 . The linear regression equation was y = 1529.72x + 2748.38 (R 2  = 0.9871), and the limit of detection reached the fg/mL level. This microarray chip features low sample consumption, high sensitivity, and high throughput, demonstrating considerable potential for non-invasive early diagnosis of AD. Graphical