Spatially Resolved Laser and Thermal Desorption/Ionization Coupled with Mass Spectrometry

The work discussed in this dissertation is aimed at creating novel approaches to chemical imaging that ultimately allow for submicron resolution. This goal has been approached from two direction using laser based desorption and coupling it with an AFM using apertureless tip-enhanced laser ablation/ionization. The second direction was through the development a new approach to thermal desorption based mass spectrometry experiments by using a proximal probe to spatially desorb the surface and ionizing the plume of neutrals using a secondary ionization source at atmospheric pressure. The thermal desorption approach allows for the easy scaling of the technique all the way from the millimeter to the nanometer regime. In the nanometer regime an AFM platform with silicon based heating AFM probes is used to locally desorb material from nanometer sized craters. The final work in this thesis focused on trying to improve laser based desorption through a secondary ionization of the neutrals plume by capturing the laser desorption plume into a liquid and then electrospaying the solution into a MS. The added benefit of being able to capture the desorption plume into a liquid is the ability to carry out post sampling processing of the captured analyte via high performance liquid chromatography. The ability to clean up a sample via HPLC also allow for the detection of isobaric compounds as well as trace level materials which otherwise would be obscured by matrix effects in complicated sample matrixes like tissues. This application of laser desorption with a secondary ionization by capture into a liquid could be envisioned to be applied to AFM based laser desorption techniques where boosting the ionization efficiency is crucial for signal detection.