Top 5 reasons to use IMS-MS

Author: Emma Marsden-Edwards

Mass spectrometry (MS) is a widely used analytical technique that measures the mass-to charge (m/z) ratio of ions. It can be coupled with ion mobility spectrometry (IMS), which provides additional differentiation through its orthogonal separation mechanism and can be used to generate information relating to the structure of analyte molecules. This structural information derives from collision cross-section (CCS) values which can be calculated for each analyte ion in a sample. The CCS value is linked to the 3D shape of an ion which is central to the differentiation of similar species. CCS values are generally reported in square ångströms (Å2), and can be derived from the length of time an ion takes to traverse an ion mobility cell. IMS technology has been around for decades, but since the advent of the first high-performance commercial IMS-MS instrument in 2006, it’s use has grown rapidly. It is now widely used in diverse fields such as the study of native proteins, pesticide analysis, metabolomics, lipidomics, proteomics, petroleomics, and for screening applications. Irrespective of this, there are some common misconceptions surrounding the technology.

This blog is here to debunk the myths! Read on to discover the top 5 reasons why IMS-MS has been indispensably weaved into the workings of laboratories across the globe, and why it might just be what’s missing from yours.

Reduction of chemical complexity

Ion mobility separation can help to reduce complexity in your mass spectra. It enables cleaner mass spectra to be obtained from analytes through general background reduction and separation of coeluting species of similar m/z values. This removal of background interference can be extremely useful in reducing any ambiguity in structural elucidation following tandem MS experiments and for ambient/direct ionization approaches where there is no prior chromatography e.g. imaging.  

Maximizing peak capacity and selectivity

Overall system peak capacity is increased through the addition of IMS. Ion mobility can help separate structural isomers, isobaric species and more broadly species of differing charge state.  With the latest IMS technology, analytes of interest can be isolated according to their mobility for closer study. As a consequence, IMS-MS can be used to effectively analyze both complex mixtures and single-molecules, combining breadth of analysis with pinpoint precision.

Analytical flexibility to couple with other techniques

IMS-MS couples well with other separation techniques such as LC and GC. Ion mobility separation typically operates on the millisecond timescale, and consequently can be nested between chromatographic separation and Tof MS analysis. Thus, the benefits of IMS-MS for improved analysis of mixtures can be obtained without detriment to the already established complementarity of chromatography and MS. [2]   Moreover, hyphenating IMS with MS can reduce analysis by enabling the use of  shorter chromatographic separations due to the added peak capacity.

Useful CCS Information: IMS provides a characteristic and reproducible measure of an analyte’s structure through derived CCS values. CCS values can be used to increase confidence in the identification of known compounds, and more generally IMS reduces interferences and improves S:N ratios. CCS can also serve as a valuable parameter in the identification of unknowns. 

Studies continue to demonstrate the utility of CCS libraries for compound identification as part of a screening workflow. As CCS measurements are made in the gaseous phase, remotely from the ion source, CCS values are unaffected by the sample matrix and are consistent between instruments and across a broad range of chromatographic experimental conditions. [1] The high precision of CCS measurements means that they can be used in combination with other molecular identifiers to increase confidence in compound identification.

Indicator of Molecular Structure.

Theoretical CCS values determined by molecular modelling may be compared directly with experimentally derived CCS values obtained by ion mobility separations. With this, you can yield useful information on the structure and shape of large proteins/protein complexes, peptides, organometallic complexes and small molecules. This information can provide unique insights into important biological and chemical processes.

…and finally, debunking the biggest myththat IMS-MS is a specialist technique, requiring advanced knowledge to both operate the system and analyze the data generated. Well, this just is not the case anymore! Improvements in hardware and software mean that IMS-MS is now available to all.  The range of IMS-MS instruments available mean you can choose a system that meets your specific requirements. Systems with streamlined instrument control, automated set-up and integrated data interpretation tools are available alongside those systems designed with more advanced capabilities and software to match. The only difficulty now is finding a reason not to use IMS-MS!

Learn more:

[1] Building a Collision Cross Section Library of Pharmaceutical Drugs Using the Vion IMS QTof Platform: Verification of System Performance, Precision and Deviation of CCS Measurements

[2] The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics