Actively-modulated SERS detection of multiple biomarkers for Alzheimer’s disease in various body fluids by piezoelectric-charge-plasmonic nanocomposite film

The early and precise monitoring of Alzheimer’s disease (AD) hinges critically on the ultrasensitive detection of low-abundance biomarkers in complex biological matrices. Herein, we developed an innovative actively-modulated surface-enhanced Raman scattering (SERS) platform by strategically integrating a piezoelectric polyvinylidene fluoride (PVDF) matrix with ZIF-67-supported silver nanoparticles (Ag NPs) for AD assay. This fascinating architecture was meticulously constructed through in-situ grow uniform two-dimensional ZIF-67 membrane onto PVDF, followed by precision sputtering of Ag NPs to improve both target enrichment and signal amplification. Remarkably, the substrate demonstrated a perfect enhancement factor over 1.03 × 10 8 under optimized piezoelectric stimulation, owing to the concerted effects of strain-induced charge polarization and intensified electromagnetic field. In practical assays, the signal of Aβ peptides was successfully triggered in tear fluid, cerebrospinal fluid (CSF), and serum using controlled pressure, effectively overcoming their diverse background interference. A pressure-dependent multiplex detection was further conducted in serum for reliable quantification of Aβ42/Aβ40 ratio. Moreover, the recovery rates of Aβ42/Aβ40 in various biological environment were all significantly improved under progressively increased pressure, demonstrating robust performance across clinically relevant biofluids. This work develops a high-performance piezoelectric-charge-plasmonic hybrid SERS substrate, which demonstrates enormous potential for intelligent detection of AD markers in clinical settings.