Ion mobility mass spectrometry of isomeric RNA biomarkers

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Joseph Njoroge Mwangi (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Norman Chiu

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 give an 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 and most of them, including microRNAs have been reported to be biomarkers for various diseases including cancer. >55 % of the currently reported human microRNAs are isomeric. Various methods used to analyze microRNAs have their limitations, for mass spectrometry, co-elution from the column of isomeric microRNAs that have close physicochemical properties is a challenge to tandem mass spectrometry. This research focused on developing an ion mobility mass spectrometry-based method geared towards resolving isomeric RNA biomarkers. However, when using ion mobility, scientists are faced by lack of a universal calibrant which can be applied across platforms and inter-laboratories. In addition, the instrument selected for this study has been reported widely in literature as causing ions to heat up in the ion mobility cell. The first project aimed at addressing the calibration limitation for ion mobility. 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 using these matrices. The second project was aimed at investigating the Effects of different modes of operation on total internal energy of ions in traveling wave ion mobility mass spectrometry. We have compared the total internal energy of selected molecular ions as they transit through the Triwave ion mobility mass spectrometry platform by use of percentage dissociation of the ions in the two Collision Induced Dissociation (CID) cells in the instrument when operated in different modes that are available on the platform. These experiments have shed some new insights into the extent of ion heating in the instrument and will be helpful with a project related with the current research in our lab.

Additional Information

Language: English
Date: 2018
Ion mobility, Isomeric, RNA, Synapt G2, Traveling wave
Ion mobility spectroscopy
Mass spectrometry
Biochemical markers

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