Accumulation and Compression of Billions of Ions using CRIMP in … · 2017. 8. 2. · May 30, 2017 Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-11885 23 Accumulation Compression

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

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


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)


May 30, 2017 4

Potential solution:

Increase ion path length

Challenges:

Drift tube IM high voltage needed

Length of drift tube needed

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

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?

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

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

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

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

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

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

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

Two new SLIM functions

May 30, 2017 14

Accumulation Compression

May 30, 2017 15


ESI Source

Trapping Ion Funnel

Accumulation limited by trap size(Volume ~3 cm3)

Conventional Ion Funnel


May 30, 2017 Deng, L. et al. Anal. Chem. 2017, Accepted 16


ESI Source

Trapping Ion Funnel



9 m section of SLIM Board(Volume ~146 cm3)

Wave MotionNo

Wave Motion

ESI Source



ESI Source

Trapping Ion Funnel




Wave MotionNo

Wave Motion

ESI Source


Ion Filling




ESI Source

Trapping Ion Funnel




Wave MotionNo

Wave Motion

ESI Source

Ion Filling




ESI Source

Trapping Ion Funnel




Wave MotionNo

Wave Motion

ESI Source

Extended Time

Ion Filling




ESI Source

Trapping Ion Funnel




Wave Motion

ESI Source

Ion Ejection Wave Motion


More than five billion ions accumulated in a 9 m SLIM region


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)

May 30, 2017 Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-11885 23


ESI Source

Trapping Ion Funnel


9 m section of SLIM board(Volume ~146 cm3)


Wave Motion

ESI Source


Halted half the time(2X compression)

ESI Source

9 m section of SLIM board

Normal Wave Motion


May 30, 2017 24


ESI Source

Trapping Ion Funnel


9 m section of SLIM board(Volume ~146 cm3)


Wave Motion

ESI Source



ESI Source


Normal Wave Motion



May 30, 2017 25


ESI Source

Trapping Ion Funnel


9 m section of SLIM bBoard(Volume ~146 cm3)


Wave Motion

ESI Source


ESI Source


Normal Wave Motion





May 30, 2017 26


ESI Source

Trapping Ion Funnel




Wave Motion

ESI Source


ESI Source

9 m section of SLIM Board

Normal Wave Motion Halted half the time(2X compression)



May 30, 2017 27


ESI Source

Trapping Ion Funnel




Wave Motion

ESI Source


ESI Source

9 m section of SLIM Board

Normal Wave Motion



Compression Evaluation


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)



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)



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

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)


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)



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

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)

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



[M+K+H]2+m/z=556

SLIM Accumulation135 m Separation


1480 1520 15600

1

LNH

cb

Drift Time (ms)

a

LNnH

130 140 1500

1

Drift Time (ms)

LNnH

LNHc

a & b



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



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

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

Accumulation and Compression of Billions of Ions using CRIMP in … · 2017. 8. 2. · May 30, 2017 Garimella, V. B. et al. Anal. Chem. 2016, 88, 11877-11885 23 Accumulation Compression

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