A surface enhanced Raman spectroscopy platform based on nanoshells for detection of beta-amyloid
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abstract
A major limitation of many surfaced enhanced Raman spectroscopy (SERS) approaches is the dependence of the Raman enhancement on the local nanostructure. While these local "hot spots" may provide areas of extremely strong enhancement, which make trace analyte detection possible, they also make quantitative measurements problematic. Gold nanoshells however, with the ratio of the radius of their silica core to gold shell tuned to the near infrared excitation wavelength, have been used as a platform for uniform SERS enhancement. By using nanoshells, the SERS enhancement is dependent on the resonance of single nanoshells, without relying on the uncontrolled contribution from localized "hot spots". The nanoshell platform is functionalized with sialic acid to mimic neuronal cells surfaces to allow for the specific binding of -amyloid, the primary protein component of the senile plaques found in Alzheimer's disease patients. We ultimately hope that this mechanism will provide insight into the relationship between the progression of Alzheimer's disease and -amyloid through detection of the toxic form of the protein with structural and concentration information. With this approach, we have obtained concentration dependent spectra, consistent across the platform surface, which indicate the feasibility of detecting -amyloid oligomers into the picomolar range. Additionally, by monitoring SERS spectra as -amyloid changes its structural conformation from monomer to fibril, we have demonstrated conformational dependence of the SERS signals.
