Application Of Ion Mobility Research Articles

Characterization of Bile Acid Isomers and the Implementation of High-Resolution Demultiplexing with Ion Mobility-Mass Spectrometry

Bile acids (BAs) are a complex suite of clinically relevant metabolites that include many isomers. Liquid chromatography coupled to mass spectrometry (LC-MS) is an increasingly popular technique due to its high specificity and sensitivity; nonetheless, acquisition times are generally 10–20 min, and isomers are not always resolved. In this study, the application of ion mobility (IM) spectrometry coupled to MS was investigated to separate, characterize, and measure BAs. A subset of 16 BAs was studied, including three groups of isomers belonging to unconjugated, glycine-conjugated, and taurine-conjugated BA classes. A variety of strategies were explored to increase BA isomer separation such as changing the drift gas, measuring different ionic species (i.e., multimers and cationized species), and enhancing the instrumental resolving power. In general, Ar, N2, and CO2 provided the best peak shape, resolving power (Rp), and separation, especially CO2; He and SF6 were less preferable. Furthermore, measuring dimers versus monomers improved isomer separation due to enhanced gas-phase structural differences. A variety of cation adducts other than sodium were characterized. Mobility arrival times and isomer separation were affected by the choice of adduct, which was shown to be used to target certain BAs. Finally, a novel workflow that involves high-resolution demultiplexing in combination with dipivaloylmethane ion-neutral clusters was implemented to improve Rp dramatically. A maximum Rp increase was observed with lower IM field strengths to obtain longer drift times, increasing Rp from 52 to 187. A combination of these separation enhancement strategies demonstrates great potential for rapid BA analysis.

Enhancing the Depth of Analyses with Next-Generation Ion Mobility Experiments.

Recent developments in ion mobility (IM) technology have expanded the capability to separate and characterize gas-phase ions of biomolecules, especially when paired with mass spectrometry. This next generation of IM technology has been ushered in by creative innovation focused on both instrument architectures and how electric fields are applied. In this review, we focus on the application of high-resolution and multidimensional IM to biomolecular analyses, encompassing the fields of glycomics, lipidomics, peptidomics, and proteomics. We highlight selected research that demonstrates the application of the new IM toolkit to challenging biomolecular systems. Through our review of recently published literature, we outline the current strengths of respective technologies and perspectives for future applications.

Benefits of ion mobility for analysing monochloropropane-diol esters

ABSTRACTThis paper reports the first application and benefits of ion mobility in combination with liquid chromatography and a transportable time-of-flight mass spectrometer to the analysis of monochloropropane-diol esters (MCPDE) in vegetable oils. The additional selectivity obtained with the ion mobility allowed the quantitative analysis of MCPDEs as such in their intact form (direct analysis) without any chemical derivatisation and, furthermore, without any enrichment or purification step. This gain in selectivity manifests primarily in the resolution of interferences originating, for example, from the diacylglycerol components of palm oil. In silico calculations confirm that resolution of such interferences would require mass resolutions higher than 200,000 at m/z 600, e.g., in the case of signals of the 41K isotope of the PO DAG and the signals of the sodiated PO MCPD. While such resolution can be obtained on certain state-of-the-art costly and laboratory-exhaustive research instruments, this study demonstrates that even transportable time-of-flight MS can achieve the required selectivity when combined with ion mobility. Further advantage of the described approach is that the applied sample preparation is only dilution with minimum consumable requirements and can be performed quickly even outside laboratories directly in the field. The described results suggest that the application of ion mobility in addition to LC-MS is likely to push the boundaries of contaminant analysis especially for high-throughput screening investigations.

Insight into Protein Conformation and Subcharging by DMSO from Native Ion Mobility Mass Spectrometry

AbstractElectrospray ionization‐mass spectrometry (ESI‐MS) interfaced with ion‐mobility (IM) spectrometry has enabled the study of protein structure and interactions under native‐like conditions. In biological assays, dimethyl sulfoxide (DMSO) is often included as a co‐solvent to dissolve organic molecules. While low levels of DMSO are known to reduce the charge of protein ions generated by ESI, the exact mechanism by which this occurs has been debated. In this study, we describe the first application of IM–MS to study the effect of DMSO subcharging on native protein conformation. We find that at low concentrations, DMSO induces modest (1‐2 %), but repeatable, reductions in protein collision‐cross sections (CCSs) of four different protein complexes, avidin, concanavalin A, alcohol dehydrogenase, and pyruvate kinase, as measured by traveling‐wave (TW) IM–MS. Individual protein charge states also experienced compaction in size, suggesting that this effect could not be attributed to the shift of charge state distribution by DMSO alone.