Access Type

Open Access Dissertation

Date of Award

January 2015

Degree Type


Degree Name




First Advisor

Sarah Trimpin


Inlet ionization and vacuum ionization are novel ionization methods to produce electrospray ionization (ESI)-like ions from the solid or liquid states, operating from atmospheric pressure (AP) or vacuum, without the use of voltage or the necessity of high energy input such as a laser or particle beam. The fundamental aspects were probed for better understanding of the novel ionization processes. Initial applications were attempted to utilize the novel ionization methods for fast, robust, and quantitative analyses.

For inlet ionizations (laserspray ionization inlet, LSII; matrix assisted ionization inlet, MAII; and solvent assisted ionization inlet, SAII), small (e.g. drugs) to large (e.g. proteins) non-volatile molecules are ionized with the assistance of heat and pressure drop, and are operated from AP. The ease of operation, rapidness of data acquisition, and simplicity of coupling with other techniques achieved by SAII, have enabled the inlet ionization for high throughput multiplexing analyses, hyphenation with liquid chromatography (especially at low flow rates), and fast surface assessment and drug quantifications. LSII has been utilized together with solvent-free sample preparation and solvent-free gas-phase separation for total solvent-free analysis.

The production of multiply charged ions from solid states by vacuum ionization was utilized to encompass the advantages from ESI and matrix-assisted laser desorption/ionization (MALDI), for better characterization from surfaces and extending the mass range of high performance mass spectrometers. Operating from AP provides the potential for vacuum ionization to be applied in high throughput analysis. The continuous ion formation also benefits matrix assisted ionization vacuum (MAIV) for drug quantification with better reproducibility.