Single cell analysis using bio-aerosol mass spectrometry: Development and applications for the real-time detection of bio-warfare pathogens

Chapter 1 introduces the threat of bio-warfare agents, specifically Bacillus anthracis (anthrax). As this dissertation concentrates on the real-time detection of Bacillus atrophaeus, a surrogate for anthrax, some background of Bacillus bacteria is given, including cell germination, growth, and sporulation.; Chapter 2 reviews the theory of time-of-flight (TOF) mass spectrometry (MS). The equations for ion motion in TOF-MS are derived. Different ion source designs are reviewed, including single and dual stage sources.; Chapter 3 describes BAMS for the real-time, reagentless characterization of individual aerosols. The BAMS mass signatures were able to distinguish two Bacillus spore species from one another as well as detect Bacillus spores against a complex background consisting of several potential hoax compounds.; In chapter 4, single vegetative cells and spores of Bacillus atrophaeus were analyzed using BAMS. Key biomarkers were identified from organisms grown in 13C and 15N isotopically enriched media.; Chapter five explains the effects of particle chemical composition on the effective ionization probability (EIP) and spectral characteristics of BAMS spectra.; Chapter six presents the SIMION modeling of the reflectron TOF BAMS. SIMION was used to access the instrument sensitivity at high masses and explain the low mass bias of the instrument.; Chapter 7 reports the sensitivity performance of the new BAMS. Particles containing MALDI matrix and analyte were used. With the new BAMS, ion signals were obtained from 14 zeptomoles (∼8400 molecules) of gramicidin S. This represents a record in sensitivity for MALDI analysis. (Abstract shortened by UMI.)...