The detection of bio-molecules (e.g. nucleic acids and proteins) is the bedrock upon which research in the life sciences and diagnostic medicine rests. For nucleic acids, the polymerase chain reaction (PCR) is the ultimate in terms of target detection sensitivity (10s - 100s of copies/sample). For proteins, the enzyme-linked immunosorbent assay (ELISA) is the most widely used and clinically useful methodology. Nanostructures have emerged as a class of materials ideally suited for biomolecular detection due to inherent physical and chemical properties that are the result of the size, shape, and composition of the structures. This thesis details my graduate work during which the novel properties of nanostructures were harnessed to address some of the limitations of current bio-molecule detection assays. Specifically, DNA-functionalized gold nanoparticles were used to develop a novel DNA and protein detection platform known as the bio-barcode assay found to have significant advantages compared to current techniques. The original description of the bio-barcode assay is presented along with subsequent work aimed at improving assay reproducibility and quantification. Following, is the first demonstration of the assay in a clinical context. Specifically, we used the bio-barcode assay to detect amyloid derived diffusible ligand (ADDL) in the cerebrospinal fluid (CSF) of individuals with a post-mortem diagnosis of Alzheimer's disease. In those patients with histopathologic findings consistent with Alzhemier's disease and given a post-mortem confirmatory diagnosis, the bio-barcode assay through the detection of ADDLs in the CSF was able to discriminate this patient population from healthy controls. Conventional immunodetection methods had failed to detect ADDLs in the same patient samples demonstrating the power of an assay with a sensitivity advantage. I then detail the use of the bio-barcode assay for the detection of prostate specific antigen (PSA) from the serum of men following prostatectomy where the serum level of PSA falls to undetectable using current immunodetection methodologies. Using the bio-barcode PSA assay, I define what the residual post-prostatectomy PSA serum value is and demonstrate that the bio-barcode assay is capable of detecting a rise in PSA concentration after prostatectomy at the earliest possible time for the potential delivery of curative adjuvant therapy.

Last modified

• 06/25/2018

Creator

• Colby Shad Thaxton

DOI

• https://doi.org/10.21985/N2T70C

Subject

• Interdepartmental Biological Sciences Program

Keyword

• biomolecular detection
• prostate
• nanoparticles
• nanotechnology

Date created

• 2007-05-11

Resource type

• Dissertation

Rights statement

• In Copyright