The Fundamental Analysis, Applications, Improvement in Sensitivity and Signal-to Noise using Inlet Ionization-Mass Spectrometry

Inlet ionization mass spectrometry (MS) is a new class of ionization methods providing multiply charged ions similar to electrospray ionization (ESI), either from solution or from a solid matrix without the need of an applied voltage, corona discharge, or an ionizing laser. Ionization occurs within the pressure drop region of a heated inlet linking atmospheric pressure (AP) with the vacuum of the mass spectrometer. The primary objective of this project is to explore the fundamental aspects of the main inlet ionization methods, improve the current sensitivity, and apply these novel techniques to real world applications. By addressing each concept, inlet ionization will be more marketable and will allow for commercial success ultimately allowing for simple and highly sensitive ionization that can be applied on any AP mass spectrometer.;The fundamentals of inlet ionization are explored studying sonic spray ionization (SSI). Similar to inlet ionization, ions are formed from a solvent/analyte solution without applied voltage and only a high velocity nebulized gas is needed to produce ions. In this study, the sensitivity was improved by 100x placing an obstruction in the path of the nebulized spray (o-SSI) and further improved by an additional 100x applying a positive or negative voltage onto the obstruction (Vo-SSI). Switching between a positive or negative polarity on the obstruction provides the added benefit for selective or inclusive ionization.;The application of various ambient ionization methods were also tested for the detection of steroids. Insights have been made in method development and successful detection of natural and synthetic anabolic steroids within consumer meat products using atmospheric solids analysis probe (ASAP). Detection of steroid standards using solvent assisted ionization inlet (SAID) was compared to ESI using liquid chromatography (LC-SAII). LC-SAII was shown to be more sensitive in terms of both limit of detection (LOD) and limit of quantitation (LOQ) than LC-ESI under optimal parameters for both methods using the same instrumentation and analyte solutions.;Improvements have also been made with the matrix-based inlet ionization techniques, laserspray ionization inlet (LSII) and matrix assisted ionization inlet (MAID, by implementing sample preparation strategies used to improve the sensitivity, detection limit, and signal-to-noise of analytes used in matrix assisted laser desorption/ionization (MALDI). The addition of ammonium salts to the LSII or MAII matrix/analyte mixture either reduced background ions or improved the overall sensitivity of the analyte by 3-4X for peptides and certain classes of small molecules, and by at least 10X for proteins. Various strong and weak acids have also been tested and added to LSII matrices. In the presence of a basic compound, all acids tested hinder analyte ionization. However, with certain acidic small molecules, the analyte abundance was improved by 2-8x in the presence of weak acid additives. Advances have also been made in understanding ionization processes by investigating the deposition and sublimation of common inlet ionization matrices and investigating the applications associated with these novel compounds.;Advances in fundamental understanding, increased sensitivity, reduction of chemical noise, and applications of inlet ionization methods presented here provides a step forward in making these methods commercially viable.