Enhancing Lipidomics With High-Resolution Ion Mobility-Mass Spectrometry

Area of Science:

• Biochemistry and Analytical Chemistry
• Lipidomics and Mass Spectrometry

Background:

• Lipids are crucial biomolecules regulating cellular functions and diseases.
• Conventional lipidomics faces limitations in resolving isomeric and low-abundance lipids.
• Ion mobility-mass spectrometry (IM-MS) offers enhanced separation, identification, and sensitivity for lipid analysis.

Purpose of the Study:

• To review transformative advances in IM-MS-driven lipidomics.
• To highlight innovations in IMS platforms, lipid identification strategies, and multi-dimensional workflows.
• To outline a roadmap for leveraging IM-MS in biomarker discovery and precision medicine.

Main Methods:

• Evaluation of leading ion mobility spectrometry (IMS) platforms and instrument geometries.
• Exploration of lipid collision cross-section (CCS) databases and predictive computational frameworks (modeling, machine learning).
• Integration of CCS with liquid chromatography-MS/MS and mass spectrometry imaging for multi-dimensional lipidomics.

Main Results:

• Significant breakthroughs in resolving lipid isomers using advanced IMS platforms.
• Development of computational tools and machine learning for high-confidence lipid annotation via CCS data.
• Emerging multi-dimensional workflows enhancing lipid identification depth and spatial resolution.

Conclusions:

• IM-MS represents a paradigm shift in lipidomics, overcoming limitations of conventional methods.
• Synergistic integration of instrumentation, computational methods, and biological insights is key to unraveling lipidome complexity.
• IM-MS is poised to accelerate biomarker discovery and advance precision medicine through comprehensive lipidome analysis.