Graduation Year

2023

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

Theresa Evans-Nguyen, Ph.D.

Committee Member

Randy W. Larsen, Ph.D.

Committee Member

Bill J. Baker, Ph.D.

Committee Member

Mathew Pasek, Ph.D.

Keywords

Differential Mobility Spectrometry, High-Field Asymmetric-waveform Ion Mobility Spectrometry, Isotope Identification, Atmospheric Pressure Chemical Ionization, Bulk Acoustic Wave Nebulization, Ion-trap Analyzer

Abstract

Field Asymmetric Ion Mobility Spectrometry (FAIMS), often coupled with mass spectrometry (MS), offers rapid analytical ion filtration, useful in reducing matrix interference and differentiating isomeric compounds. This study focuses on augmenting FAIMS-MS analyses through the incorporation of gas phase solvents, or "modifiers," inducing dynamic microsolvation, a particularly potent method of analysis enhancement.

Initially, the research utilized a bubbler-based system, incorporating a humidity sensor, improving modifier concentration control when using water. Our application in opioid detection and differentiation revealed considerable advancements. Notably, an increased peak capacity in an opioid mixture and successful separation of the isobaric opioid pair, alfentanil and ortho-isopropyl furanyl fentanyl, were observed. However, inherent reproducibility issues limited the system to water utilization.

To address these limitations, we developed an innovative system using ultrasonic nebulization and precision pumping for facilitated solvent delivery. The system offered heightened control and flexibility, enabling in-depth evaluations of the influence of modifier concentrations on the FAIMS-MS analysis of opioids. Modifiers generally employed are polar protic solvents, like water or isopropyl alcohol, which bind tightly to analytes, potentially enhancing resolving power. We explored alternatives, using solvents like pyridine, toluene, and cyclohexane, allowing more subtle interactions targeting specific classes of analytes, specifically the aromatic functionality in opioids.

Additionally, we delved into the development of a continuous ambient desorption/ionization source for FAIMS, the ultrasonic nebulization corona discharge (USN-CD). Developed via modification of the USN-based modifier system, it demonstrated superior signal intensities compared to standard nano electrospray ionization sources for heroin and fentanyl. However, thermal degradation issues arose with more thermally labile biomolecular compounds. Mitigating this requires further development, crucial for establishing USN-CD as a viable universal ionization source.

Altogether, this research not only deepens our understanding of the implementation and progression of ancillary apparatus in FAIMS-MS but also pioneers the pathway for future innovations. It forms a robust base for the advancement of FAIMS technology, particularly in refining the analysis of opioids, while also broadening its potential for diverse applications.

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