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

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 similar to 13m path length for high-resolution IM (HRIM) separations. The resolving power (CCS/Delta CCS) 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 reversed-sequence 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 (similar to 50). In general, the SLIM IM-MS platform is capable of resolving peaks separated by as little as similar to 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.

Automated summary

The SLIM IM platform demonstrated high-resolution separations for a range of isomeric and isobaric compounds, achieving resolving powers exceeding 300 and enabling the separation of peaks as close as 0.6%. Low CCS measurement biases (<0.5%) were obtained under high resolving power conditions, making it suitable for global untargeted applications requiring broadband HRIM separations.