Ultra-sensitive, label-free probing of the conformational characteristics of amyloid beta aggregates with a SERS active nanofluidic device

One of the primary pathological hallmarks of Alzheimer’s disease is the formation of neutric plaques in the brain. The aggregation of amyloid beta peptide (Ab) is central to the formation of these plaques and thus trace detection and characterization of these aggregates can have significant implications for understanding and diagnosing diseases. Here we have demonstrated a label-free surface enhanced Raman scattering technique combined with nanofluidics that is able to sensitively detect Ab aggregates and to characterize their structural and surface properties at concentrations that are much lower than the limit of detection of existing instrumentation. With our device we have successfully detected Ab aggregates formed at a very low concentration range of 10 fM to 1 lM and shown that the extent of protein aggregation and its resulting conformational characteristics are dependent on the initial Ab concentration. The ability to observe the early stages of the aggregation process with analytical techniques, like that demonstrated here, could help to develop a better understanding of the conditions which lead to conformational disease, such as neurodegenerative diseases.