Enabling technologies for high performance mass spectrometry applications

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Mass spectrometry (MS) has become the most preferred analytical tool because of its superior sensitivity and resolution, as well as the structural information it provides. Of the currently available MS methods, liquid and gas chromatography (LC and GC) coupled with MS have been the most widely used. However, LC/GC-MS in many cases suffer from long analysis time and low sensitivity, that increase the cost of analyses and prohibit the use of MS in many situations that could have helped by the MS technology, such as food, environmental and pharmaceutical analysis, as well as its application in clinical and point of care settings. The proposed research program aims to address some major issues that are impeding the application of MS methods and make some of the currently time-consuming methods high throughput, and improve the performance other MS methods. Applications of the new methods for the study of protein structure and structure dynamics are proposed. Sample extraction and sample enrichment often determine the quality of the analytical methods and their successful implementation. We will explore the use of new solvent systems such as deep eutectic solvents with mechanochemical method for solute specific extraction and enrichment. New liquid and solid extraction methods will be developed for ambient ionization mass spectrometry (AIMS) detection to speed up the analytical process while maintaining sensitivity and specificity. We will focus on one of the AIMS technologies called direct analysis in real time mass spectrometry (DART-MS). The combination of the extraction systems with AIMS will allow us to analyze environmental and biological samples in much shorter times than the currently used LC-MS methods. Physicochemical properties of the solvents and the solids, and their interaction with the analytes will be studied, as well as the effect of these properties on the ionization and detection efficiency of AIMS. For more complex systems a separation step must be added before the analytes are introduced into the MS. We will continue to develop novel methods to use capillary electrophoresis mass spectrometry (CEMS). Of particular interest is our efforts in capillary isoelectric focusing (cIEF) MS. We have demonstrated that this method is feasible, and our next step is to explore the possibility of combining IEF with tandem mass spectrometry for the study of minute structural differences in protein isomers. CE-MS can be a powerful tool for the study of protein structural dynamics and conformation changes in solution in their native states. We will develop new method to monitor the hydrogen-deuterium exchange (HDX) to characterize the part of the protein molecules that are exposed to the solution, and the parts of that are protected by their tertiary structures, as well as their conformational changes and disulfide bonds scramble in different kind of stress conditions.