U.S. Department of Energy

Pacific Northwest National Laboratory

Structures for Lossless Ion Manipulations (SLIM) traveling wave SUPERhigh resolution IM-MS for lipidomics

Introduction 

Despite advances in lipidomic separations and mass spectrometry based techniques, analysis of lipid isomers continues to pose analytical challenges. Ion mobility (IM) is an important tool for isomer separations, however, low resolution of commercial IM devices limits their utility for the analysis of lipid isomers with small structural differences.  Herein we evaluate a new multi-pass travelling wave ion mobility (TWIM) structures for lossless ion manipulations (SLIM) platform for enhanced separations of lipid and glycolipid isomers.  In addition to an expandable path length, this platform features compression ratio ion mobility programming (CRIMP) technology, allowing accumulation of large ion populations and compression of ion mobility peaks. The new platform is expected to significantly enhance sensitivity and resolution of lipid isomer separations. 

Methods 

Preliminary experiments were performed on an expandable path length SLIM platform coupled with an Agilent 6224 TOF MS and controlled by in-house developed data acquisition software. Infusions of lipid standards and mixtures were combined with TWIM separations performed at 2 to 2.5 Torr pressures. The platform featured a short 1.3 m path as well as a 14.7 m serpentine path, which, with application of switches, can be expanded for multiple passes of ions of a targeted mobility range. The new SLIM platform to be evaluated features a 1.2 m pre-scan path and a 12.5 m serpentine path equipped with 2 travelling wave inputs, enabling application of CRIMP technology 
  
Preliminary data 

In the initial applications of the multi-pass SLIM TWIM-MS platform, we investigated separations of up to 60 m path lengths for the analysis of selected lipid isomers in positive ion mode. The 16 m TWIM path  length resulted in  baseline resolution of  two fatty acyl double bond positional isomers of diacylglycerophosphocholine (PC) with less than 1% difference in their collision cross-sections (PC(18:1(6Z):18:1(6Z)) and PC(18:1(9Z):18:1(9Z)). Additionally, baseline separations were achieved for PC isomers with cis/trans double bond orientations as well as the GD1a and GD1b ganglioside isomers. We plan to utilize CRIMP technology in the new multi-pass SLIM TWIM platform for additional lipid isomers with distinct double bond locations and orientations, fatty acyl chain positions, and glycan subunit configurations in standards and biological mixtures. CRIMP technology enables the accumulation of >109 ion populations in the SLIM device, therefore greatly increasing charge capacity of the multi-pass SLIM TWIM platform. CRIMP compression capability alleviates IM peak broadening associated with increasing SLIM TWIM path lengths without significant loss of resolution. We anticipate that the new platform will enable lipid isomer TWIM separations with significantly enhanced sensitivity and high resolution for much longer path lengths.

Novel aspect

Innovative ion mobility platform for ultra-high resolution, ultra-sensitive ion mobility separations of structurally similar lipid isomers.

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