Silver nanoparticle-based SERS sensors for sensitive detection of amyloid-β aggregates in biological fluids

One of the hallmarks of Alzheimer's disease (AD) pathogenesis is the production, aggregation, and deposition of amyloid-β (Aβ) peptide. Surface-enhanced Raman spectroscopy (SERS) is a promising analytical technique capable of providing valuable information on chemical composition and molecule conformations in biological samples. However, one of the main challenges for introducing the SERS technique into the practice is preparation of scalable and at the same time stable nanostructured sensors with uniform spatial distribution of nanoparticles. Herein, we propose SERS platforms for reproducible, sensitive, label-free quantification of amyloid-β aggregates for short-wavelength - 532 and 633 nm - lasers. A SERS sensor - based on silver nanoparticles immobilized into a chitosan film (AgNP/CS) - provided a uniform distribution of AgNPs from a colloidal suspension across the SERS sensor, resulting in nanomolar limits of detection (LODs) for Aβ42 aggregates with a portable 532 nm laser. The laser-induced deposition was used to obtain denser periodic plasmonic sensors (AgNP/LID) with a uniform nanoparticle distribution. The AgNP/LID SERS sensor allowed for 15 pM LOD for Aβ42 aggregates with 633 nm laser. Notably, both nanostructured substrates allowed to distinguish amyloid aggregates from monomers. Therefore, our approach demonstrated applicability of SERS for detection of macromolecular volumetric objects as amyloid-β aggregates for fundamental biological studies as well as for "point-of-care" diagnostics and screening for early stages of neurodegenerative diseases.