Alzheimer's disease (AD), a neurodegenerative disease and the most common cause of dementia, affects 4.5 million
people according to the 2000 US census and is expected to triple to 13.2 million by the year 2050. Since no definitive
pre-mortem tests exist to distinguish AD from mild cognitive impairment due to the natural aging process, we focus on
detecting the beta amyloid (Aβ) protein, the primary component of the senile plaques characteristic of AD. We
specifically detect cytotoxic species of Aβ by exploiting surface enhanced Raman scattering (SERS). Using a
nanofluidic device with a bottleneck shape (a microchannel leading into a nanochannel); we trapped gold colloid
particles (60 nm) at the entrance to the nanochannel, with Aβ restricted within the interstices between the aggregated
nanoparticles. The continuous flow generated from pumping the solution into the device produced size-dependent
trapping of the gold colloid particles, resulting in a high density of aggregated nanoparticles at this precise region,
creating localized "hot spots" in the interstitial region between nanoparticles, and shifting the plasmon resonance to the
near infrared region, in resonance with incident laser wavelength. With this robust sensing platform, we were able to
obtain concentration-dependent SERS spectra of Aβ and of different proteins present in the cerebrospinal fluid of
healthy people and people with Alzheimer's disease.
The Raman scattering signature of molecules has been demonstrated to be greatly enhanced, on the order of 106-1012
times, on roughened metal surfaces and clustered structures such as aggregated colloidal gold. Here we describe a
method that improves reproducibility and sensitivity of the substrate for surface enhanced Raman spectroscopy (SERS)
by using a nanofluidic trapping device. This nanofluidic device has a bottle neck shape composed of a microchannel
leading into a nano channel that causes size-dependent trapping of nanoparticles. The analyte and Au nanoparticles, 60
nm in diameter, in aqueous solution was pumped into the channel. The nanoparticles which were larger than the narrow
channel are trapped at the edge of the channel to render an enhancement of the Raman signal. We have demonstrated
that the Raman scattering signal enhancement on a nanochannel-based colloidal gold cluster is able to detect 10 pM of
adenine, the test analyte, without chemical modification. The efficiency and robustness of the device suggests potential
for single molecule detection and multicomponent detection for biological applications and/or biotoxins.
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