Date of Award

Spring 2023

Project Type


Program or Major


Degree Name

Doctor of Philosophy

First Advisor

Anyin AL Li

Second Advisor

W. Rudolf WS Seitz

Third Advisor

Glen GM Miller


The introduction of electrospray ionization (ESI) in the 1980s has had a significant impact on the field of liquid chromatography-mass spectrometry (LC-MS), enabling the qualitative and quantitative analysis of small molecules in complex biological and environmental samples. NanoESI, developed in 1993, further improved sensitivity and reduced sample consumption. However, the detection limits for some environmental contaminants, such as perfluorooctanoate sulfonate (PFOS), require ppt-level detection, which necessitates preconcentration. Solid-phase microextraction (SPME) is a commonly used technique, and liquid-liquid extraction has shown promising results for water samples. Recently, the Li group has discovered femtoampere and picoampere ionization modes of ESI, which have shown practical benefits such as improved microsample utilization and reduced contamination. In the first part, the ESI characteristics of a non-polar solvent were investigated using femtoampere and picoampere modes. Direct ESI-MS was used to rapidly analyze perfluorinated sulfonic acid (PFS) analytes in drinking water samples. By using femtoampere and picoampere modes in ESI, detection limits of 0.38-5.1 ppt and a quantitation range of 5-400 ppt were achieved for perfluorinated sulfonic compounds in drinking water samples. The second part of the study focused on the charge state distribution of model protein ions in femtoampere ESI under different pH conditions. The study found that signal intensities of proteins were 4 orders of magnitude lower in femtoampere mode than the nanoampere mode, and the average charge state was about 1-2 charge states lower. The addition of 0.1% formic acid into the solution in femtoampere mode increased the average charge state of proteins to the same level as that in nanoampere mode. The study proposed that the less acidic environment protein experienced in femtoampere mode may be attributed to fewer fission events compared to nanoampere mode.