Statistically quantified measurement of an Alzheimer's marker by surface‐enhanced Raman scattering

Fibrillar forms of the Amyloid‐β (Aβ) protein have been implicated in the early stages of Alzheimer's disease (AD), however there are no standardised assays for soluble Aβ oligomer biomarkers that provide the best indication of the disease progression [1,2]. As a step towards a fast and label‐free method for testing different AD biomarkers, we have combined laser nano‐textured substrates with a SERS mapping technique and validated it using soluble Aβ‐40 oligomers [3‐5]. The nano‐textured SERS substrates provide fast (&5 min), label‐free spectra associated with soluble Aβ‐40 oligomers down to a concentration of 10 nM. Statistical analysis of the spectral intensities mapped over the substrate surface shows a quantitative correlation with the oligomer concentration. Schematics of experiments: SERS mapping of Aβ‐40 (left figure: measured SERS intensity overlayed with an SEM image of ripples) was carried out on the laser nano‐textured (ripple) surface of sapphire and statistical analysis of the SERS intensity was carried out for qualitative (a high SERS intensity at low probability) and quantitative (a moderate SERS intenisty at the highest probability) measures. Quantitative statistical analysis of SERS mapping data can be performed off line for cross correlations with other known SERS signatures. It is shown that Surface Enhanced Raman Scattering (SERS) provides the quantitative correlation between the analyte concentration and SERS intensity. Statistical analysis of SERS intensity measured at high spatial resolution from larger areas with cross sections of tens‐of‐micrometers provides a novel label‐free analytical tool for high sensitivity detection of amyloids – the markers of Alzheimer's disease.