1 research outputs found
Development of a SLIM SUPER TWIM-MS Application Platform for Multi-Omics (ASMS 2017)
<p>Structures for lossless ion
manipulations (SLIM) have been recently developed for traveling wave ion
mobility (TWIM) experiments with a range of capabilities including serpentine
long path separations (>100 m), trapping of large ion populations (>10<sup>9</sup>
ions), and compression ratio ion mobility programming (CRIMP) for increased
sensitivity. These capabilities have demonstrated remarkable improvements in
separation of isomeric lipids, peptides, and metabolites. </p>
In this work, we
evaluate the development of a SLIM TWIM-MS platform specifically designed for application
in multi-omic analysis of complex biological samples. This system is designed
to overcome challenges in conventional IM-MS analysis, including the ability to
precisely target a narrow mobility window for extended analysis. This
presentation will highlight the hardware and software innovations required for
such experiments.A homebuilt SLIM system, coupled with Agilent 6538 QTOF-MS, is evaluated
for its capabilities in ultrahigh resolution IM separations. The custom SLIM utilizes
four different traveling wave (TW) inputs, designed for multiple accumulation
regions and peak compression. Switches are placed to allow multiple passes of
ions within a targeted mobility range and to control trapping events.
Instrument control and data acquisition are performed with in-house developed
software. Experiments involve a one pass (12.3 m path length) prescan to obtain
initial drift time information and mass spectra. A targeted range is then
selected for further analysis, which can include multiple separation passes for
improved resolution followed by compression to reduce diffusional broadening
and prevent excessive narrowing of the mobility range studied. The SLIM IM-MS applications
system is evaluated for its capabilities in the analysis of complex mixtures,
specifically for accumulation of a large initial ion population, concentration
of a targeted mobility range, and long path separations providing improved
resolution.
<p>Acquisition of a prescan
(small ion population, single pass separation) produces initial drift time
information and mass spectra to define regions of interest. A user-defined
experiment (i.e., number of passes, compression, etc.) then begins with accumulation
of a large initial ion population in a 6 m region; preliminary experiments have
demonstrated SLIM accumulation of >10<sup>9</sup> ions using low-amplitude
TWs. The ability to accumulate such a large ion population provides increased
dynamic range for the analysis of complex mixtures, in which key components may
be present at low concentrations. This SLIM-based trapping capacity overcomes
the challenge of limited ion capacity encountered in conventional pulsed IM
instrumentation. </p>
<p>The in-house developed
software can then control TW parameters and switches for precision control of
trapping, cycling, and compression as per the defined experiment. Single pass SLIM
(performed with a similar SLIM design having a 13 m separation path) has
demonstrated dramatic improvements in resolution with increased path length for
isomeric cis/trans lipids, leucine/isoleucine-containing peptides, reverse
sequence peptides, and metabolites such as sugars. Multiple pass separations,
with path lengths in excess of >100 m, provide further improvements in
resolution and the detection of previously unobserved conformers. In addition,
CRIMP has demonstrated increased signal intensity by merging several adjacent
traveling traps. This reduces the effects of diffusional broadening that occur
with long path separations and improves sensitivity for trace components in mixtures.These capabilities
are integrated into a multi-pass serpentine ultra-long path for extended
resolution (SUPER) SLIM TWIM-MS system that will be evaluated for analysis of
complex biological samples with a multi-omic approach (e.g., metabolomics,
proteomics, lipidomics).</p