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Structures for Lossless Ion Manipulations (SLIM) traveling wave SUPER high resolution
IM-MS for lipidomics
Biological Sciences Division, Pacific Northwest National Laboratory
R. Wojcik, I. K. Webb, Y. M. Ibrahim, J. E. Kyle, K. J. Bloodsworth, S. Garimella, A. Hamid, E. S. Baker, R. D. Smith
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LIPIDOMICS – complexity due to structural diversityLipid Maps database: >40,000 entries owing to progress in:
- Front end chromatographic separations- High resolution mass spectrometry- Fragmentation and ion-molecule reaction techniques for structural elucidation
2Shevchenko et al, 2010, Nature Reviews Molecular Cell Biology, 11, 593-598
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LIPIDOMICS – ongoing analytical challenges
Han et al, 2016, Progress in Lipid Research, 61, 83–108J.P. Koelmel et al, 2017, Biochimica et Biophysica Acta, 2017, in pressHankock et al, 2017, Analytical Biochemistry, 524, 45-55
• Improper lipid annotations
• Isobaric/isotopic interferences
• No universal method for structural elucidation
• Low peak capacity; low throughput of front-end separations
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IM-MS for lipid separation and structural elucidation
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• Ions move in an electric field through a drift path and interact with a buffer gas • Fast separations, precise drift times• Distinct collisional cross section (CCS) trend lines for lipid classes • Separation of isomeric/isobaric lipids feasible
Kliman et al, 2011, Biochim. Biophys. Acta, 1811, 935–945 ; Kyle et al, 2016, Analyst, 141, 1649–1659
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Challenges for IM-MS lipid analyses
Kyle et al, 2016, Analyst, 141, 1649–1659
• Limited peak capacity• Insufficient resolution of isomers/isobars• Co-elution even with front-end LC
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Resolution in IM-MS
• Resolution between ions depends on differences in their mobilities
• Selectivity – type of gas, dopants
• Physical parameters – temperature, pressure
• Instrumental factors – path length L and E profile across L
• E profile differs among IM MS techniques
• Resolution ~ 𝐿𝐿
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High V
Low V
DC guard DC guard
DC guard DC guard
RF RF RF RF
RF RF RF RF
Ion confinement for IM-MS in Structures for Lossless Ion Manipulations (SLIM)
y
x
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y z
x
High VLow V
Traveling Waves (TW) in SLIM for ion transport in IM-MS
TW
TW
TW
xz
TW A
mpl
itude
(V)
Hamid et al, 2015, Anal. Chem., 87, 11301−11308
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SLIM TW Serpentine Ultra-long Path with Extended Routing (SUPER) High Resolution IM-MS
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• Lossless transmission - straight paths and 90° turns
• Serpentine path for TW IM-MS
Multi-fold resolution enhancement vs DT IM-MS
• Multi-pass SLIM SUPER IM with expandable path length
Resolution increases with square root of path length
Hamid et al, 2015, Anal. Chem., 87, 11301−11308Deng et al, 2016, Anal. Chem., 88 (18), pp 8957–8964Wojcik et al, 2017, Int. J. Mol. Sci., 18, 183Deng et al, 2017, Anal. Chem.,89 (8), pp 4628–4634
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TW SLIM SUPER IM-MS platform
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+ 1.3 m = ~ 16 m - full mobility range
SUPER long path ~ 15 m x number of passes + 1.3 m - selected mobility range
pass
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1. PC16:1(9Z)/16:1(9Z) 2. PC16:1(9E)/16:1(9E)
phosphocholine fatty acid cis/trans isomerswith 16 meter SLIM IM-MS
1 2
DT IM-MS 16 m SLIM TW IM-MS
400 410 420 4300
1
Nor
mal
ized
inte
nsity
Drift time (ms)
1
2
34 36 38 400
1
Nor
mal
ized
Inte
nsity
Drift time (ms)
(M+H)+
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Phosphocholine fatty acid double bond positional isomers with 16 meter SLIM IM-MS
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1. PC18:1(6Z)/18:1(6Z) 2. PC18:1(9Z)/18:1(9Z)
1 2
16 m SLIM TW IM-MSDT IM-MS
36 38 40 420
1
Nor
mal
ized
inte
nsity
Drift time (ms)460 480 500
0
1
Drift time (ms)
Nor
mal
ized
inte
nsity
1
2
(M+H)+
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Ganglioside (head group) isomerswith 16 meter SLIM IM-MS
13
1,2
(M-2H)2-1: GD1b (36:1) 2: GD1a (36:1)
DT IM-MS 16 m SLIM TW IM-MS
1,2 - mixture
36 40 440
1
Nor
mal
ized
inte
nsity
Drift time (ms)300 320 340 3600
1
Nor
mal
ized
inte
nsity
Drift time (ms)
1 3 - mixture
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SLIM IM-MS – brain polar lipid extractNegative ion mode
m/z
m/z
1.3 meter SLIM 16 meter SLIM
Drift time (ms) Drift time (ms)
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SLIM IM-MS – brain polar lipid extractganglioside isomers (Gd1a, Gd1b)
m/z
Drift time (ms)
m/z
Drift time (ms)
((GD1b (36/2) ((GD1a (36/2)
1.3 meter SLIM 16 meter SLIM
(M-2H)2-
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Drift time (ms)
m/z
Drift time (ms)
SLIM IM-MS – brain polar lipid extract, glycerophospholipids
m/z
1.3 m SLIM 16 m SLIM
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PC(16:0/20:3)_A/B/CPC(18:1/18:2)(M-CH3)-
SLIM IM-MS – brain polar lipid extract, glycerophospholipids
Drift time (ms)
m/z
PG(16:0/18:1) ?PA(18:0/22:6) ?
Drift time (ms)
m/z
Drift time (ms)
1.3 meter SLIM 16 meter SLIM
1.3 m SLIM 16 m SLIM
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Multi-pass TW-SLIM SUPER IM-MS of lipid isomers
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PC (16:1(9Z)/16:1(9Z) – 275.3 Å2PC (16:1(9E)/16:1(9E) – 276.7 Å2
0 50 100 150 200 250 300
1.0
1.5
2.0
2.5
3.0
3.5re
solu
tion
path length (meters)
PresenterPresentation Notes
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Summary
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• SLIM SUPER TW IM-MS platform enhances resolution in ion mobility separations of lipid species, isomers
• SLIM SUPER IM-MS has broad applicability for separation and structural characterization of lipids in mixtures
Future directions• Ultrasensitive and ultrahigh resolution SUPER SLIM (R.D. Smith, WP 346)• Compression Ratio Ion Mobility Programming (CRIMP) (S. Garimella, WP 349)• CRIMP for greater sensitivity and dynamic range of SLIM SUPER IM-MS
(L. Deng, ThOG 3:30 pm)• 3 dimensional (multi-level) SLIM to increase path lengths and peak capacities for
full mobility range analyses (A. Hamid, ThP 400)
Y.M. Ibrahim et al., 2017, Anal. Chem., 89 (3), 1972–1977
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Acknowledgements
National Institute of General Medical SciencesBiomedical Technology Research Resource at PNNL
DOE Office of Biological and Environmental Research
PNNL SLIM and IM-MS team
Lipid team: Jennifer E. Kyle, Kent J. Bloodsworth
Structures for Lossless Ion Manipulations (SLIM) traveling wave SUPER high resolution �IM-MS for lipidomicsLIPIDOMICS – complexity due to structural diversityLIPIDOMICS – ongoing analytical challengesIM-MS for lipid separation and structural elucidationChallenges for IM-MS lipid analysesResolution in IM-MS Ion confinement for IM-MS in �Structures for Lossless Ion Manipulations (SLIM)Traveling Waves (TW) in SLIM for ion transport in IM-MS SLIM TW Serpentine Ultra-long Path with Extended Routing (SUPER) High Resolution IM-MSTW SLIM SUPER IM-MS platform�phosphocholine fatty acid cis/trans isomers�with 16 meter SLIM IM-MS �Phosphocholine fatty acid double bond positional isomers with 16 meter SLIM IM-MS Ganglioside (head group) isomers�with 16 meter SLIM IM-MS SLIM IM-MS – brain polar lipid extractSLIM IM-MS – brain polar lipid extract�ganglioside isomers (Gd1a, Gd1b)SLIM IM-MS – brain polar lipid extract, �glycerophospholipidsSLIM IM-MS – brain polar lipid extract, �glycerophospholipidsMulti-pass TW-SLIM SUPER IM-MS of lipid isomersSummaryAcknowledgements
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