Date of Award

2011

Level of Access

Campus-Only Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor

Touradj Solouki

Second Committee Member

Scott Collins

Third Committee Member

Howard H. Patterson

Abstract

In this dissertation we aimed to: (1) improve and use the capabilities of Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometers equipped with external ion sources coupled to a gas chromatograph (GC) and a nano liquid chromatograph (nano LC) for wide mass range analyses of biomarkers, (2) use computer simulations to investigate (a) the challenges associated with injection of small mass ions into a strong magnetic field (in FT-ICR instruments) and (b) the utility of ICR image charge detection for assessing a novel superconducting magnet design for improving mass measurement accuracy (MMA) and mass resolving power (MRP) of FT-ICR instruments. Chapter 1 includes a brief introduction to state-of-the-art FT-ICR mass spectrometry and an overview of the goals of this dissertation as they relate to biomarker discovery using non-invasive biological samplings for small and large molecule analyses. In chapter 2, we discuss the experimental details and practical approaches for construction and evaluation of low-cost high-frequency RF power supplies for ion injection into 7.0 tesla and 9.4 tesla FT-ICR mass spectrometers via quadrupole ion guides and external ion sources. The importance of mass measurement accuracy (MMA) and ultrahigh mass resolving power (MRP) for confident analysis of small molecules are also discussed in this chapter. In chapter 3, theoretical results from computer simulations (using SIMION) on examining fine trajectories of small mass ions (i.e., m/z 28-300) in a quadrupole ion guide (housed in an experimentally measured magnetic field gradient of 9.4 tesla superconducting magnet) are presented. Improvements to potential ion guide devices for biomarker discovery are discussed in this chapter. The challenges and details on coupling a nano LC system to an 9.4 tesla ESI/FT-ICR MS are presented in chapter 4. Moreover, details on newly devolved novel salivary protein library for protein/peptide identification solely based on MMA of FT-ICR are presented. In chapter 5, we investigate the presence of informative large stress biomarkers such as proteins, peptides and their post-translational modified forms in human saliva. In this interdisciplinary approach, we evaluate biomedical efficacy of using potential biomolecules as stress and placebo response biomarkers. In chapter 5, we utilized the technology presented in chapter 4 to provide an in-depth characterization of the most abundant proteins in whole human saliva samples. In Chapter 6, we present our newly developed and implemented image charge detection scheme/model based on Shockley-Ramo theorem in ICR cell using SIMION software. We use this model for initial evaluation of a novel magnet design for FT-ICR mass spectrometers in order to improve the MMA and MRP. Chapter 7 includes a summary of current limitations, prospective solutions, and future directions in the field of biomarker identification in general and non-invasive sampling in biomedicine in particular.

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