Advanced strategies for imaging mass spectrometry and ion mobility - mass spectrometry
Forsythe, Jay Garrett
The overarching goal of this research is to explore novel approaches to mass spectrometry (MS) analysis in order to address current challenges in the technique. The primary focus of this document is nanostructure-initiator mass spectrometry (NIMS), an ionization technique which utilizes porous silicon substrates to absorb ultraviolet laser energy, desorb analytes into the gas-phase, and ionize them for mass spectrometry. This technique is essentially a form of matrix-assisted laser desorption/ionization (MALDI), a commonly-used method in which molecules absorb laser energy and help to ionize the sample. However, two primary limitations of MALDI are that it is difficult to analyze small molecules and that sample preparation can be laborious. In contrast, NIMS is currently optimized for MS imaging of small analytes such as metabolites and requires minimal sample preparation. In this document, two novel NIMS approaches are described: (1) the development and optimization of semi-transparent NIMS thin films which allow for MS and optical imaging of biological cells; and (2) the evaluation of perfluorinated matrices which interact with the NIMS substrate to ionize larger (kDa) analytes of interest. Additionally, this document explores one example of how structural MS methods can be useful in separating regioisomers with identical masses. Methylenedianiline (MDA) is a mixture of small isomeric compounds. Using ion mobility - MS (IM-MS) in conjunction with computational modeling, MDA structural isomers are differentiated and their relative gas-phase stabilities are determined. It was found that the differences in gas-phase stability between isomers were structural in nature, related to the site of protonation during the ionization process.