Development of transmission mode desorption electrospray ionization (TM-DESI)
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A new era of high-throughput mass spectrometry emerged with the nearly simultaneous introduction of two ambient ionization techniques: desorption electrospray ionization (DESI) and direct analysis in real time (DART). The ability to integrate near instantaneous sample analysis with the specificity of mass spectrometry opened up a broad range of applications. While some of these involve the direct analysis of bulk materials, many others require the collection and deposition of samples onto suitable substrates. This dissertation details the development of a new mode of operation for DESI. Instead of depositing a sample onto a continuous surface, the sample is either collected by or deposited onto a mesh substrate. Analytes either adsorb to the mesh strands or become suspended within the confines of the mesh in macroscale droplets. The samples are then analyzed by scrolling the mesh orthogonally into the path of an electrospray plume positioned coaxial to the inlet capillary of the mass spectrometer, thereby resulting in the transmission of the ionizing plume directly through the material. The transmission mode results in desorption and ionization typical of DESI, but with the added benefits of a simpler experimental geometry and the convenient analysis of both dry (i.e., following evaporation of the deposition solvent) and wet (i.e., solvated) samples. The simplification of the experimental arrangement increases method robustness and reproducibility, while the inclusion of a mesh substrate introduces new possibilities for sample collection and introduction, due to the intricate chemistry between the mesh material, analytes, and deposition/electrospray solvent system. However, the most important benefit lies in the development of surface-enhanced TM-DESI, whereby mesh substrates are derivatized to specifically capture and concentrate targeted analytes directly from solution. Following removal of matrix interferences by sample rinsing and subsequent cleavage of a photolabile linker, the mesh is analyzed directly by TM-DESI-MS. The technique has the potential to overcome interferences that have typically required chromatographic separations using LC-MS or have been insurmountable using ambient ionization methods. The impact of the surface-enhanced method could be tremendous as it may ultimately unite the competing metrics of analytical speed and specificity for ambient ionization mass spectrometry.