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Joseph Mwangi

Posted on April 4, 2018


Date - April 4, 2018
1:00 pm - 2:00 pm


PhD Dissertation Seminar CHE 752
Title: “Ion mobility mass spectrometry of isomeric RNA biomarkers.”
Advisor: Dr. Norman Chiu


“Ion mobility mass spectrometry of isomeric RNA biomarkers.”

Dissertation Abstract

Ion mobility spectrometry is an analytical technique that separates gaseous ions depending on their mobility in a gas filled cell under the influence of an electric field. More compact ions transit through the cell more easily than elongated ions of the same mass. Ions with a higher charge state also transit faster than those with lower charge states. When coupled to mass spectrometry, which separates ions according to their mass to charge ratios, the synergistic platform becomes a more reliable analytical technique, Ion Mobility Mass Spectrometry (IM-MS), which can provide additional information of the samples being analyzed. More importantly, the ability to resolve structural isomers is a very pertinent aspect of this analytical technique. Ribonucleic acid, RNA is one of the two nucleic acids besides Deoxyribonucleic acid, DNA. DNA stores the genetic information of an organism while RNA transfers the genetic information from the DNA for protein synthesis.  There are various types of RNAs which includes mRNA, tRNA, rRNA piRNA and microRNAs. Most of the RNAs undergo modifications which can result in isomeric RNA fragments during their analysis. microRNAs and modified RNAs have been reported to be biomarkers for various diseases including cancer. In one of our publications we have established that the extent of isomerism in human microRNAs is >55 % of the currently reported human microRNAs. Various methods used to analyze RNAs have their limitations, for mass spectrometry, co-elution from the column of isomeric modified or unmodified RNAs which have similar physicochemical properties is an analytical challenge. My research focused on developing an ion mobility mass spectrometry-based method geared towards resolving isomeric RNA biomarkers. When using ion mobility, scientists are faced by lack of a universal calibrant which can be applied across platforms and inter-laboratories. A project aimed at addressing the calibration limitation for ion mobility was undertaken. To address this issue, we have used MALDI (Matrix Assisted Laser Desorption Ionization) matrices to develop a reference method that can potentially be applied across different platforms and in different laboratories. In addition, the instrument selected for this study, Synapt G2 by Waters™ has been reported widely in literature as causing heating of ions in the ion mobility cell.  In another project, we investigated the effects of different modes of operation on total internal energy of ions in traveling wave ion mobility mass spectrometry. We have used a simpler and easily applicable method to asses the total internal energy of the ions as they traverse through the Synapt G2 which is useful to anyone using the instrument.