The Liquid Microjunction-Surface Sampling Probe as an Emerging Tool for Medicinal Mass Spectrometry

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Authors

McKeown, Mark J.

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thesis

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eng

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3D Imaging , 4D Imaging , Mass Spectrometry , Underwater analysis , Uneven surface analysis

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Ambient ionization mass spectrometry (AIMS) is an attractive technique for providing supplementary information that medical professionals can use to guide clinical decisions. The group of techniques includes ionization methods, such as desorption electrospray ionization (DESI) and rapid evaporative ionization mass spectrometry (REIMS) that, when combined with mass spectrometry (MS) analyze thousands of compounds (e.g., highly polar/non-volatile, non-polar/volatile analytes) within resected tissues. From these compound profiles, one can distinguish between healthy and diseased states on a cellular level. Tissue analysis by MS is difficult to perform as it is challenging to obtain the required data from these specimens while minimizing the loss of information from time-dependent metabolomic changes. Despite technological advances, many AIMS techniques are limited in processing speed, analyte extraction, and sample restraints for widespread clinical utility. Herein, the liquid microjunction- surface sampling probe (LMJ-SSP) is investigated in profiling and imaging MS to directly interrogate fresh tissue surrogates of various sizes/shapes/thicknesses. A previously developed conductive feedback system is enhanced and used with the probe to produce four-dimensional (4D) images that describe the topography and chemistry of uneven surfaces using the LMJ-SSP. The platform enables the analysis of these tissue specimens with absolute height variations of up to centimeters, and the ability to monitor the dynamics of changing surfaces. Secondly, the versatility of the LMJ-SSP is explored to profile underwater tissue surrogates. To this end, normal saline solutions (water and 0.9% sodium chloride, weight by volume [w/v]) are typically used to temporarily maintain tissue integrity before analysis. The two described workflows use a low miscible solvent to directly interrogate these specimens immersed in saline solutions or extract compounds from saline microenvironments. Submerged analytes are still identifiable for their molecular weights at high salt concentrations (0 - 3.5% NaCl, w/v). Underwater analysis of an insoluble compound reveals the effects of salt on electrospray ionization (ESI). The LMJ-SSP provides the speed of information needed to revolutionize patient care and outcomes.

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