Studies on surface-assisted laser desorption/ionization and its analytical application in imaging mass spectrometry

Abstract

Surface-Assisted Laser Desorption/Ionization Mass Spectrometry (SALDI-MS) is an analytical technique enabling direct chemical analysis of solid samples. Analytes could be desorbed/ionized upon nitrogen laser irradiation from a SALDI substrate-coated sample, then analyzed by MS. The substrate is involved in the transfer of laser energy to the analytes, and eventually assists the desorption/ionization of analytes. The analytical performance of SALDI-MS, such as detection sensitivity, is dependent on different parameters of the substrate, such as size, morphology and form. In this thesis, the effects of several substrate parameters on the SALDI process were investigated. SALDI-MS based Imaging Mass Spectrometry (IMS) method was also developed using efficient SALDI substrate identified in the fundamental studies. IMS is a chemical-specific mapping technique which allows parallel mapping of multiple analytes in solid samples.

The desorption mechanism of SALDI is investigated using two groups of substrate, the carbon allotropes and the noble metal nanoparticles. Ion desorption efficiency and internal energy transfer were probed and correlated in carbon-based SALDI. It was found that the ion desorption efficiency and internal energy transfer was in opposite order. Substrate that transferred more internal energy to ions did not show higher ion desorption efficiency. This result could not be explained by the Thermal Desorption model which was a generally believed mechanism of the SALDI desorption process. A non-thermal model, the Phase Transition model is proposed to account for the

SALDI desorption process. The Phase Transition model suggests that the substrate is melted/ restructured upon laser irradiation, and this will assist ion desorption. The Phase Transition model is supported by the morphological change of carbon substrates after SALDI and high initial velocity of ions desorbed by carbon-based SALDI (> 1,000 ms-1).

SALDI-MS is useful for small molecule analysis due to the relatively clean

background in the low mass region. SALDI-IMS is developed and applied to the imaging of spatial distribution of small molecules in forensic and biological samples. Gold nanoparticles (AuNPs) was selected as the substrate from several other noble metal NPs. A solvent-free method, argon ion sputtering, was employed for coating AuNPs on sample surface prior to SALDI-IMS analysis. Fine details of the samples, such as the fine pattern of latent fingerprints and handwriting on questioned documents can be preserved and imaged reliably by avoiding the use of solvent. Fatty acids, drugs and ink components can be imaged in forensic samples including latent fingerprints, banknotes and checks. The solvent-free SALDI-IMS method was also applied to image the distribution of metabolites in intact animal tissues. Spatial distributions of neurotransmitters, nucleobases and fatty acids can be imaged from mouse brain and tumor tissue sections.