Nanofluidic biosensing for beta-amyloid detection /
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| Format: | Thesis eBook |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University],
[2010]
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| Online Access: | Link to OAK Trust copy |
| Abstract: | A nanofluidic biosensor using surface-enhanced Raman scattering (SERS) was developed to detect the B-amyloid (AB) protein, one of the biomarkers of Alzheimer's disease (AD). Recent studies have indicated that investigating changes in relative concentrations of structure specific AB oligomers in cerebral spinal fluid (CSF) during the progression of AD could be important indicators for diagnosing AD pre-mortem. However, there is no definitive pre-mortem diagnosis of AD thus far because of the lack of technology available for sensitive AB detection. Hence, the development of a system for detecting the structure specific AB oligomers, along with the concentrations of these oligomers in CSF, would be useful in the investigation of the molecular mechanisms of AB cytotoxicity associated with AD. In this thesis, a nanofluidic trapping device trapping system for detecting biomolecules at sub-picomolar concentrations was developed for using SERS. The device, with a microchannel leading to a nanochannel, carries out dual functions: encouraging size dependent trapping of gold nanoparticles (60nm) at the entrance of the nanochannel as well as restricting the target molecules between the gaps created by the aggregated nanoparticles. Initially, the trapping capability of the nanofluidic device was tested using fluorescent polystyrene and gold nanoparticles. UV-vis absorption spectroscopy was used to characterize the gold nanoparticle clusters at the entrance to the nanochannel. The device established controlled, reproducible, SERS active sites within the interstices of gold nanoparticle clusters and shifted the plasmon resonance to the near infrared, in resonance with incident laser light. Two strongly Raman active molecules, adenine and Congo red, were used to test the feasibility of the SERS nanofluidic device as a platform for the detection of multiple analytes. The results showed that strong SERS signals were obtained from the nanoparticle clusters at the nanochannel entrance. Once the feasibility of the approach was determined with strong Raman molecules, AB was detected using this nanofluidic SERS platform. Distinct surface-enhanced Raman spectra of AB was observed in different conformational states as a function of concentration and structure (monomer versus oligomer form) due to AB refolding from a-helical to a predominantly B-pleated sheet form. The sensor was also shown to potentially distinguish AB from insulin and albumin, confounder proteins in cerebral spinal fluid. Thus, a novel platform was developed to detect picomoler levels of AB with the ultimate goal of facilitating the diagnosis and understanding of Alzheimer's disease by means of detecting structure specific oligomers of AB. |
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| Item Description: | "Major Subject: Biomedical Engineering" Title from author supplied metadata (automated record created 2010-03-12 12:08:51). Electronic resource. |
| Physical Description: | 1 online resource. |
| Bibliography: | Includes bibliographical references. |