Resolving Power and Collision Cross Section Measurement Accuracy of a Prototype High-Resolution Ion Mobility Platform Incorporating Structures for Lossless Ion Manipulation

Abstract

A production prototype structures for lossless ion manipulation ion mobility (SLIM IM) platform interfaced to a commercial high-resolution mass spectrometer (MS) is described. The SLIM IM implements the traveling wave ion mobility technique across a ∼13m path length for high-resolution IM (HRIM) separations. The resolving power (CCS/ΔCCS) of the SLIM IM stage was benchmarked across various parameters (traveling wave speeds, amplitudes, and waveforms), and results indicated that resolving powers in excess of 200 can be accessed for a broad range of masses. For several cases, resolving powers greater than 300 were achieved, notably under wave conditions where ions transition from a nonselective "surfing" motion to a mobility-selective ion drift, that corresponded to ion speeds approximately 30−70% of the traveling wave speed. The separation capabilities were evaluated on a series of isomeric and isobaric compounds that cannot be resolved by MS alone, including reversedsequence peptides (SDGRG and GRGDS), triglyceride double-bond positional isomers (TG 3,6, 9 and TG 6,9,12), trisaccharides (melezitose, raffinose, isomaltotriose, and maltotriose), and ganglioside lipids (GD1b and GD1a). The SLIM IM platform resolved the corresponding isomeric mixtures, which were unresolvable using the standard resolution of a drift-tube instrument (∼50). In general, the SLIM IM-MS platform is capable of resolving peaks separated by as little as ∼0.6% without the need to target a specific separation window or drift time. Low CCS measurement biases <0.5% were obtained under high resolving power conditions. Importantly, all the analytes surveyed are able to access high-resolution conditions (>200), demonstrating that this instrument is well-suited for broadband HRIM separations important in global untargeted applications.

Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments

“…21 The use of various IMS technologies together with tandem MS has been reported for the analysis of isomeric glycans, including positional isomers. [22][23][24][25][26][27][28][29][30][31][32] While ultrahigh-resolution IMS based on structures for lossless ion manipulation (SLIM) 33,34 has been applied to achieve separation of different kinds of glycan isomers, 35,36 the assignment of a drift peak to a precise isomeric form often remains elusive. 35,37 We have previously demonstrated that cryogenic vibrational spectroscopy can be used for the identification of glycan isomers based on their unique infrared (IR) absorption spectrum.…”

Investigating the Structure of α/β Carbohydrate Linkage Isomers as a Function of Group I Metal Adduction and Degree of Polymerization as Revealed by Cyclic Ion Mobility Separations

“…While new dissociation methods (e.g., electron-based ones, charge transfer dissociation, and ultraviolet photodissociation) have shown promise for the characterization of various carbohydrate isomers, − better front-end MS separations are still needed to aid in the deconvolution of complex spectra and in data interpretation. Ion mobility spectrometry paired with mass spectrometry (i.e., IMS–MS) is both a rapid alternative and an orthogonal complement to condensed-phase separations. − In IMS–MS, ions are separated in the gas phase under the presence of an electric field based on their size/structure (i.e., their ion mobility) and charge. − Recent technological developments such as with trapped ion mobility spectrometry (TIMS), structures for lossless ion manipulations (SLIM), and cyclic ion mobility spectrometry (cIMS) have greatly increased the achievable IMS resolving power (on the order of 100s), ,− thus enabling widespread adoption in omics-based research as well as for the rapid separation of certain isomeric species.…”

Propagating Error through Traveling-Wave Ion Mobility Calibration

“…Additionally, beyond the Waters Synapt platform, other TWIMS devices are becoming commercially available. We expect to see an increase in agreement between experimental TW CCS and literature DT CCS values when using error propagation for any of these TWIMS instruments that require calibration, such as in structures for lossless ion manipulations (SLIM) − or cyclic IM-MS . This method of error propagation can be formatted to fit any type of mathematical equation, thus allowing for incorporation of all uncertainties that would arise from experimentation and data analysis.…”