High-resolution ion mobility based on traveling wave structures for lossless ion manipulation resolves hidden lipid...

Area of Science:

• Analytical Chemistry
• Biochemistry
• Lipidomics

Background:

• High-resolution ion mobility coupled with mass spectrometry (IM-MS) is crucial for resolving isobaric and isomeric interferences in complex samples.
• Conventional ion mobility (IM) techniques, such as traveling wave IM and drift tube ion mobility (DTIM), have limited resolving power (~50).
• Drift tube ion mobility (DTIM) is the gold standard for obtaining collision cross section (CCS) values directly, while traveling wave IM requires calibration.

Purpose of the Study:

• To evaluate the separation capabilities of a traveling wave ion mobility structures for lossless ion manipulation (SLIM) platform integrated with mass spectrometry (SLIM IM-MS).
• To compare the performance of SLIM IM-MS with DTIM-MS for analyzing lipid isomer standards and complex lipid samples.
• To curate a high-resolution IM lipid structural atlas using advanced separation techniques.

Main Methods:

• Cross-platform analysis of seven subclass-specific lipid extracts using both DTIM-MS and SLIM IM-MS.
• Evaluation of separation capabilities under high-resolution IM conditions (resolving power > 200).
• Two-step calibration procedure for SLIM IM to align ^TW(SLIM)CCS values with ^DTCCS reference values (within 2% average bias).

Main Results:

• High-resolution SLIM IM-MS revealed additional structural features in all lipid extracts compared to conventional IM techniques.
• The number of CCS-aligned features resolving into additional peaks varied from 5% to 50% depending on the lipid subclass.
• A total of 225 lipid features were identified using accurate mass-to-charge, CCS, retention time, and linear mobility-mass correlations.

Conclusions:

• High-resolution ion mobility, particularly SLIM IM-MS, significantly enhances the resolution of isomeric lipids, revealing greater complexity than previously observed.
• The study demonstrates the utility of SLIM IM-MS for lipidomics, providing a valuable tool for structural elucidation.
• These findings highlight the necessity of employing multiple high-resolution separation stages for comprehensive lipidomic analysis.