Derivatization of Aldehyde-Containing Molecules with Hydrazide Reagents on Tissue Surfaces for Enhanced Detection with MALDI-MSI
Tissue imaging involves slicing a section of tissue from key organs such as the brain, kidney, liver, and lungs and aims to identify chemical or morphological features unique to disease or damage. Matrix assisted laser desorption-ionization (MALDI) mass spectrometry (MS) is becoming an increasingly popular choice for imaging methods thanks to its sensitivity and high spatial resolution. Analytes are detected based on their m/z (mass-to-charge) ratios. Most analytes can be detected as a protonated adduct carrying a +1 charge, but some molecules are difficult to protonate and thus poorly detected without chemical intervention. Molecules which have a low molecular weight or are present only in low abundance are also poorly detected due to spectral congestion from endogenous molecules. In the current method, small molecules that contain an aldehyde moiety were derivatized using hydrazide reagents to create charged hydrazone derivatives with a mass increase. Aldehyde standards were first derivatized in solution before applying reagents to mouse tissue. Internal standards were incorporated into tissue by creating homogenized tissues with standard solutions. An isotopically enhanced hydrazide reagent solution was applied to tissue to create an easily recognizable doublet in derivatized analytes. Additionally, reagent was applied via solid gelatin cubes to minimize analyte delocalization. Overall, this project serves as a proof of concept for the future application of derivatizing agents containing isotopically enhanced species via solid gelatin vehicles. This can be applied to diseases in which small metabolites are produced, such as small reactive aldehydes which are produced in type II diabetes mellitus.
Research Area | Presenter | Title | Keywords |
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Cancer Studies | Shukla, Shriya | Imaging (0.833333), Imaging (0.833333), Imaging (0.833333), Imaging (0.833333), Imaging (0.833333) | |
Chemistry and Materials Science | Heron, Daniel | mass spetrometry | |
Globalization and Development | Kirkman, Elizabeth J. | Privatization | |
Globalization and Development | Mian, Samina | Privatization | |
Globalization and Development | Lescovitz, Eve Lyn | privatization |