Electronic Theses and Dissertations

Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemistry

Committee Chair

Xiaohua Huang

Committee Member

Yongmei Wang

Committee Member

Paul Simone

Committee Member

Tomoko Fujiwara

Abstract

Gold nanoparticles (AuNPs) are remarkable agents for biological detection due to their facile surface modification, optical enhancement, and biocompatibility. These characteristics encourage the development of new methods for biological detection. Of particular interest, in the field of biological detection, is the ability to detect, quantify, and characterize circulating biomarkers. Circulating biomarkers include classes of biological analytes such as cells, extracellular vesicles, proteins, DNAs, and RNAs. The ability to detect and characterize such analytes gives clinicians two significant advantages in diagnosing diseases. One advantage is diagnosis by means of a non-invasive biopsy, as circulating biomarkers may be isolated and detected from a patients blood. A second major advantage is earlier detection than what is provided by a traditional tissue biopsy. For example, many cancers go undetected until the disease has metastasized, significantly limiting chances of a successful treatment outcome. However, biomarkers that reflect the molecular contents of the tumor are being released into the bloodstream, even in early stages of tumorigenesis. Hence, the ability to detect and characterize such biomarkers would lead to earlier detection and potentially a better treatment outcome. In this dissertation, we explore the unique properties of AuNPs that enable their use as agents for circulating biomarker detections. In addition, we highlight recent methods utilizing AuNPs for biological detection. Next, we report on our method for the isolation, detection and characterization of circulating tumor cells using core-shell iron oxide-gold nanoparticles (IO-Au NPs). This method combines magnetic capture, microfluidics, fluorescence and surface enhanced Raman scattering (SERS) spectroscopy for detection and multicolor characterization of circulating tumor cells. Additionally, we report on a study to optimize the cellular binding of ligand-conjugated AuNPs. In this study we undertake a rigorous effort to design ligand-conjugated AuNPs that feature high degrees of specificity and reproducibility. Finally, we demonstrate a method of AuNP-enhanced enzyme-linked immunosorbent assay (ELISA) designed for detection of antibodies to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARSCoV2). Our enhanced ELISA method gives an approximately 100-fold increase in sensitivity over traditional ELISA methods, and also shares the agility of traditional ELISA that allows detection of a multitude of analytes.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

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