Alex Shvartsburg, Wichita State University
High-Definition Differential Ion Mobility Separations forProteomics, Metabolomics,
and Structural Characterization Using Isotopic Shifts
Faculty Host: Prof. Valentine
With all the power of modern MS, most biological and environmental analyses require
substantial prior separations. The traditional chromatography and electrophoresis
are now increasingly complemented by ion mobility spectrometry (IMS) in gases.
The nonlinear method of differential or field asymmetric waveform IMS (FAIMS)
based on the difference between mobilities at high and low electric fields is
much more orthogonal to MS than linear IMS based on absolute mobility, which
enables exceptionally specific separations. We will cover the foundations of
high-resolution FAIMS/MS and its exemplary applications. A major focus in proteomics
is localization of post-translational modifications in mixtures of isomeric proteoforms
(variants), where MS/MS is limited by lack of unique fragments. Variants with
various PTMs are effectively disentangled by FAIMS and then identified by ETD.
All D-amino acid containing peptides (DAACP) are likewise resolved from L-analogs.
A similar challenge in metabolomics is elucidating the isomeric diversity of
lipids that comprises multiple types including transacylation, double bond position,
and cis/trans geometry. High-definition FAIMS generally resolves over ~80% of
lipid isomers across types, and more in conjunction with OzID for double bond
localization. Finally, FAIMS can resolve isotopomers and isotopologues with peak
shifts dependent on the geometry in a way parallel to NMR, enabling a fundamentally
new approach to molecular structure characterization. Substantial orthogonality
between FAIMS and Linear IMS enables 2-D separations of exceptional specificity.
Shvartsburg Group Website