Matrix-Assisted Laser Desorption Electrospray Ionization: Fundamental Principles and Applications Towards Molecular Imaging

The past decade has shown numerous advancements in the field of Ambient Mass Spectrometry. Every year there have been new iterations of existing ionization sources as well as the continued development of new methods of producing ions under atmospheric pressure conditions. Among these ambient ionization techniques is a source that was developed in the Muddiman lab in 2005 that combines features and attributes of the two most commonly used ionization methods for biological analysis. By fusing electrospray ionization with matrix-assisted laser desorption ionization, the matrix assisted laser desorption electrospray ionization (MALDESI) technique demonstrates the advantages to hybrid ionization methods.;Along with advancements in instrumentation, including ionization methods as well as developments in mass analyzer technology, there have also been new ways to apply these scientific innovations to answer complex biological problems. The ability to obtain spatial information of unlabeled analyte with the specificity of mass spectrometric detection in the growing field of mass spectrometry imaging has had a significant impact on a number of research areas including drug development, biomarker discovery, and clinical diagnostics.;This work describes the path along the development of a novel ionization source from inception to its continued advancement and application to real world problems. The initial goals involved optimizing the technology to determine the limits of what the source is capable of. Along the way MALDESI was improved to allow for the ability to perform mass spectrometry imaging. With this new enhancement, MALDESI has been utilized to determine the distribution of dosed drugs within tissue sections. This spatial information can provide insight into the pharmacokinetic and pharmacodynamic properties of the drug.;In addition to its application in mass spectrometry imaging, the MALDESI source also displays potential as a direct analysis technique. The ambient nature of MALDESI makes it well suited for fast analyses with minimal sample preparation. One such application of these capabilities of MALDESI is shown in the direct analysis of dyed fabric and fibers. This experiment can be performed in seconds and provide valuable information about the identity of the dye as well the fabric polymer type.;Undoubtedly, the MALDESI technology will continue to improve and advance along with other developments in mass spectrometry. New methods of analysis and applications are bound to be developed providing avenues for MALDESI to discover other practical uses.