Trace detection of the conformational transition of beta-amyloid peptide (Abeta) from a predominantly alpha-helical structure to beta-sheet could have a large impact in understanding and diagnosing Alzheimer's disease. We demonstrate how a novel nanofluidic biosensor using a controlled, reproducible surface enhanced Raman spectroscopy active site was developed to observe Abeta in different conformational states during the Abeta self-assembly process as well as to distinguish Abeta from confounder proteins commonly found in cerebral spinal fluid.
We have developed an optofluidic device that improves the sensitivity of surface enhanced Raman spectroscopy (SERS) when compared to other SERS approaches. This device has a pinched and step microchannel-nanochannel junction that can trap and assemble nanoparticles/target molecules into optically enhanced SERS active clusters by using capillary force. These SERS active clusters provide an electromagnetic enhancement factor of approximately 10(8). In addition, due to the continuous capillary flow that can transport nanoparticles/target molecules into the junction sites, the numbers of nanoparticles/target molecules and SERS active sites are increased. As a result, the detection limit of SERS for adenine molecules was better than 10 pM.
Currently, no methods exist for the definitive diagnosis of AD premortem. β-amyloid, the primary component of the senile plaques found in patients with this disease, is believed to play a role in its neurotoxicity. We are developing a nanoshell substrate, functionalized with sialic acid residues to mimic neuron cell surfaces, for the surface-enhanced Raman detection of β-amyloid. It is our hope that this sensing mechanism will be able to detect the toxic form of β-amyloid, with structural and concentration information, to aid in the diagnosis of AD and provide insight into the relationship between β-amyloid and disease progression. We have been successfully able to functionalize the nanoshells with the sialic acid residues to allow for the specific binding of β-amyloid to the substrate. We have also shown that a surface-enhanced Raman spectroscopy response using nanoshells is stable and concentrationdependent with detection into the picomolar range.
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