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Accumulation and Compression of Billions of Ions using
CRIMP in SLIM Significantly Improves Sensitivity and Ion Mobility Resolution
Liulin Deng, Sandilya V. B. Garimella, Ahmed M. Hamid, Ian K. Webb, Xueyun Zheng, Roza Wojcik, Spencer A. Prost, Gordon A. Anderson, Erin S. Baker, Yehia M. Ibrahim,
Richard D. Smith
Biological Sciences Division, Pacific Northwest National Laboratory
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Ion Mobility (IM) Separations
Ion mobility can distinguish species based upon shapes
May 30, 2017 2
velocity is constant
v = K E
K = ion mobility
E
in out
Drift Time
Pulse of 2 ions with
same m/z but different
shape
Different conformers separate
in time with peak heights representing
the amount of each
Drift Cell
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Ion Mobility (IM) Separations
May 30, 2017 3
What can ion mobility do?
Separate ions by shape, mass and charge state
Distinguish different classes of compounds
Separate different isomers or conformations of a single m/z
Address increased sample complexity when coupling with LC and MS
Limitation
Low resolving power of conventional IM (~50-250)
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Ion Mobility (IM) Separations
May 30, 2017 4
Potential solution:
Increase ion path length
Challenges:
Drift tube IM high voltage needed
Length of drift tube needed
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Traveling Waves (TW)
May 30, 2017 Hamid, A. M. et al. Anal. Chem. 2015, 87, 11301−11308 5
Ions “quantized” into TW bins
“TW bin”
Low TW amplitude
Potentially unlimited length
Use of traveling waves eliminates the need for increasingly high voltages as the drift length increases
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IM in Structures for Lossless Ion Manipulations (SLIM)
May 30, 2017 6
Electrodes patterned on two parallel surfaces
Ions confined in an electric field conduit; potentials applied (color representation) to move ions
‘Ion Conduit’
Volts
Challenge:
How to extend the ion drift path?
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IM in Structures for Lossless Ion Manipulations (SLIM)
May 30, 2017
Hamid, A. M. et al. Anal. Chem. 2016, 88, 8949−8956
Deng, L. et al. Anal. Chem. 2016, 88, 8957−8964 7
3 mm gap
Serpentine path Electrode arrays on two mirror image surfaces
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SLIM IM-MS
May 30, 2017 Deng, L. et al. ChemistrySelect. 2016, 1, 2396−2399 8
Ion Funnel Trap
SLIM
Rear Ion Funnel
IM separation approach coupled to MS
13 meter path
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High IM resolution achieved
May 30, 2017 Deng, L. et al. ChemistrySelect. 2016, 1, 2396−2399 9
24 26 280
1
Drift Time (ms)
560 580 6000
1
Drift Time (ms)
Reverse peptide sequences:
(Ser-Asp-Gly-Arg-Gly + H)+ and (Gly-Arg-Gly-Asp-Ser + H)+
90 cm Drift Tube IM 13 m SLIM IM
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High peak capacities achieved
May 30, 2017 10
550 heavy labeled peptidesPeak capacity ~250
Deng, L. et al. Anal. Chem. 2016, 88, 8957−8964
13 m SLIM IM
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Multi-pass Serpentine Ultra-long Path with Extended Routing (SUPER) IM
May 30, 2017 11
To recycle
MS
Switch ON
Switch OFF
DC
Ion switch
Deng, L. et al. Anal. Chem., 2017, 89, 4628-4634
SLIM switch routes ions for additional passes through serpentine path
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Challenges of long path IM separations
May 30, 2017 12
500 meters130 meters13 meters
IM resolution increases, but signal intensities drop and peak widths increase
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Improving Sensitivity
Improving ion transmission to IM
Eliminating ion losses
Using larger ion populations
Compression of IM peaks
May 30, 2017Deng, L. et al. Anal. Chem. 2017, Accepted
Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-1188513
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Two new SLIM functions
May 30, 2017 14
Accumulation Compression
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May 30, 2017 15
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
Conventional Ion Funnel
Two new SLIM functions
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May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 16
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
Conventional Ion Funnel
9 m section of SLIM Board(Volume ~146 cm3)
Wave MotionNo
Wave Motion
ESI Source
Two new SLIM functions
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May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 17
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
Conventional Ion Funnel
9 m section of SLIM Board(Volume ~146 cm3)
Wave MotionNo
Wave Motion
ESI Source
Accumulation Compression
Ion Filling
Two new SLIM functions
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May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 18
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
Conventional Ion Funnel
9 m section of SLIM Board(Volume ~146 cm3)
Wave MotionNo
Wave Motion
ESI Source
Accumulation Compression
Ion Filling
Two new SLIM functions
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May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 19
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
9 m section of SLIM Board(Volume ~146 cm3)
Conventional Ion Funnel
Wave MotionNo
Wave Motion
ESI Source
Ion Filling
Two new SLIM functions
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May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 20
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
9 m section of SLIM Board(Volume ~146 cm3)
Conventional Ion Funnel
Wave MotionNo
Wave Motion
ESI Source
Extended Time
Ion Filling
Two new SLIM functions
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May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 21
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
9 m section of SLIM Board(Volume ~146 cm3)
Conventional Ion Funnel
Wave Motion
ESI Source
Ion Ejection Wave Motion
Two new SLIM functions
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More than five billion ions accumulated in a 9 m SLIM region
May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 22
0 20 40 60 80
0
2
4
6
Accumulation Time (s)
Num
ber
of C
harg
es (
bill
ion)
R2: 0.9998
IFT: Charge capacity: ~20 million(Linear range: ~1 million)
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May 30, 2017 Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-11885 23
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
9 m section of SLIM board(Volume ~146 cm3)
Conventional Ion Funnel
Wave Motion
ESI Source
Ion Ejection Wave Motion
Halted half the time(2X compression)
ESI Source
9 m section of SLIM board
Normal Wave Motion
Two new SLIM functions
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May 30, 2017 24
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
9 m section of SLIM board(Volume ~146 cm3)
Conventional Ion Funnel
Wave Motion
ESI Source
Ion Ejection Wave Motion
Halted half the time(2X compression)
ESI Source
9 m section of SLIM board
Normal Wave Motion
Two new SLIM functions
Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-11885
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May 30, 2017 25
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
9 m section of SLIM bBoard(Volume ~146 cm3)
Conventional Ion Funnel
Wave Motion
ESI Source
Ion Ejection Wave Motion
ESI Source
9 m section of SLIM board
Normal Wave Motion
Two new SLIM functions
Halted half the time(2X compression)
Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-11885
-
Two new SLIM functions
May 30, 2017 26
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
9 m section of SLIM Board(Volume ~146 cm3)
Conventional Ion Funnel
Wave Motion
ESI Source
Ion Ejection Wave Motion
ESI Source
9 m section of SLIM Board
Normal Wave Motion Halted half the time(2X compression)
Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-11885
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Halted half the time(2X compression)
May 30, 2017 27
Accumulation Compression
ESI Source
Trapping Ion Funnel
Accumulation limited by trap size(Volume ~3 cm3)
9 m section of SLIM Board(Volume ~146 cm3)
Conventional Ion Funnel
Wave Motion
ESI Source
Ion Ejection Wave Motion
ESI Source
9 m section of SLIM Board
Normal Wave Motion
Two new SLIM functions
Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-11885
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Compression Evaluation
May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 28
100 150 200 250 3000.0
0.3
0.6Io
n C
urr
en
t (n
A)
100 ms ion band
No Compression
Drift Time (ms)
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Compression Evaluation
May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 29
100 150 200 250 3000.0
0.3
0.6Io
n C
urr
en
t (n
A)
100 150 200 250 3000.0
0.3
0.6
Ion
Cu
rre
nt
(nA
)100 ms ion band
2X Compression
No Compression
Drift Time (ms)
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Compression Evaluation
May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 30
100 150 200 250 3000.0
0.3
0.6Io
n C
urr
en
t (n
A)
100 150 200 250 3000.0
0.3
0.6
Ion
Cu
rre
nt
(nA
)
100 150 200 250 3000.0
0.3
0.6
Ion
Cu
rre
nt
(nA
)100 ms ion band
4X Compression
Drift Time (ms)
2X Compression
No Compression
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100 150 200 250 3000.0
0.3
0.6
Ion C
urr
en
t (n
A)
100 150 200 250 3000.0
0.3
0.6Io
n C
urr
en
t (n
A)
Compression Evaluation
May 30, 2017 31
100 150 200 250 3000.0
0.3
0.6
Ion
Cu
rre
nt
(nA
)
50X Compression
20X Compression
10X Compression
Deng, L. et al. Anal. Chem. 2017, Accepted
Drift Time (ms)
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Compression Evaluation
May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 32
0 10 20 30 40 50
0
5
10
15
20
25
Initia
l fw
hm
/Ob
se
rve
d f
wh
m
Compression Ratio (CR)
R2: 0.9994
Excessive compression
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Integration of ion accumulation and IM peak compression in SLIM
May 30, 2017 Struwe, W. B. et al, Chem. Commun., 52, 12353-12356, 2016 33
Lacto-N-hexaose (LNH)
Lacto-N-neohexaose (LNnH)Both molecules have identical LC retention times
HPLC chromatograms (C18)
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May 30, 2017 Deng, L. et al. Anal. Chem., 2017, 89, 4628-4634 34
[M+K+H]2+m/z=556
IFT Accumulation 13 m Separation
130 140 1500
1
Drift Time (ms)
LNnH
LNHc
a & b
Integration of ion accumulation and IM peak compression in SLIM
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May 30, 2017 Deng, L. et al. Anal. Chem., 2017, 89, 4628-4634 35
[M+K+H]2+m/z=556
SLIM Accumulation135 m Separation
IFT Accumulation 13 m Separation
1480 1520 15600
1
LNH
cb
Drift Time (ms)
a
LNnH
130 140 1500
1
Drift Time (ms)
LNnH
LNHc
a & b
Integration of ion accumulation and IM peak compression in SLIM
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May 30, 2017 Deng, L. et al. Anal. Chem., 2017, 89, 4628-4634 36
1480 1520 15600
1
LNH
cb
Drift Time (ms)
a
LNnH
1480 1500 15200
1
Drift Time (ms)
LNH
cba
LNnH
[M+K+H]2+m/z=556
130 140 1500
1
Drift Time (ms)
LNnH
LNHc
a & b
SLIM Accumulation135 m Separation2X Compression
SLIM Accumulation135 m Separation
IFT Accumulation 13 m Separation
Integration of ion accumulation and IM peak compression in SLIM
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Conclusions
Ion accumulation and IM peak compression achieved in SLIM
More than 5 billion ions accumulated in a 9 m SLIM trapping region
Ion population compression limited only by space charge
Improved sensitivity and IM resolution achieved using SLIM SUPER IM
May 30, 2017 37
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Acknowledgements
May 30, 2017 38
National Institute of General Medical SciencesBiomedical Technology Research Resource at PNNL
DOE Office of Biological and Environmental Research
PNNL SLIM and IM-MS team