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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.
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This content will become publicly available on August 13, 2026
Enhancing Lipidomics With High‐Resolution Ion Mobility‐Mass Spectrometry
ABSTRACT Lipids, indispensable yet structurally intricate biomolecules, serve as critical regulators of cellular function and disease progression. Conventional lipidomics, constrained by limited resolution for isomeric and low‐abundance species, has been transformed by ion mobility‐mass spectrometry (IM‐MS). This technology augments analytical power through enhanced orthogonal separation, collision cross‐section (CCS)‐based identification, and improved sensitivity. This review examines the transformative advances in IM‐MS‐driven lipidomics, focusing on three major pillars: (1) a critical evaluation of leading ion mobility spectrometry (IMS) platforms, emphasizing innovative instrument geometries and breakthroughs in resolving lipid isomers; (2) an exploration of lipid CCS databases and predictive frameworks, spotlighting computational modeling and machine learning strategies that synergize experimental data with molecular representations for high‐confidence lipid annotation; (3) emerging multi‐dimensional lipidomics workflows integrating CCS with liquid chromatography‐MS/MS to boost identification and depth, alongside mass spectrometry imaging for spatially resolved lipidomics. By unifying cutting‐edge instrumentation, computational advances, and biological insights, this review outlines a roadmap for leveraging IM‐MS to unravel lipidome complexity, catalyzing biomarker discovery and precision medicine innovation.
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- Award ID(s):
- 2108223
- PAR ID:
- 10656494
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- PROTEOMICS
- ISSN:
- 1615-9853
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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