Abstract
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 (Aβ) 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 Aβ 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 Aβ aggregates formed at a very low concentration range of 10 fM to 1 μM and shown that the extent of protein aggregation and its resulting conformational characteristics are dependent on the initial Aβ 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.
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Acknowledgments
The authors acknowledge funding from and access to the facilities of the Nanobiotechnology Center (NBTC), an STC Program of the National Science Foundation under Agreement no. ECS-9876771. The authors also appreciate access and use of the Cornell Nanoscale Science and Technology Facility, which is supported by the National Science Foundation under grant ECS-9731293. I. Choi was partially supported by a grant from the National Research Foundation of Korea Grant funded by the Korean Government [NRF-2009-352-D00053].
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Choi, I., Huh, Y.S. & Erickson, D. Ultra-sensitive, label-free probing of the conformational characteristics of amyloid beta aggregates with a SERS active nanofluidic device. Microfluid Nanofluid 12, 663–669 (2012). https://doi.org/10.1007/s10404-011-0879-1
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DOI: https://doi.org/10.1007/s10404-011-0879-1