Conceptualization and Analytical Performance of a New ESI-MS Interface for

Structures for Lossless Ion Manipulations (SLIM)

Tsung-Chi Chen, Ian K. Webb, Marques B. Harrer, Spencer A. Prost, Randolph V. Norheim, Brian L. Lamarche, Xinyu Zhang, Jonathan T. Cox, Sandilya Garimella, Yehia M. Ibrahim,

Keqi Tang, Aleksey V. Tolmachev, Erin S. Baker, Gordon A. Anderson and Richard D. Smith

Pacific Northwest National Laboratory

Introduction

DC

DC

RF+DC

What are Structures for Lossless Ion Manipulations (SLIM)?

SLIM devices use RF and DC fields to manipulate ionsThe manipulations include moving forward/backward, turning, switching, mobility separations, etc.The planar surfaces are readily fabricated using printed circuit board (PCB) technologies

Applications of SLIM include extended sequences of manipulations, that involve separations, reactions, storage, accumulation, etc.

The Need for Efficient transfer of Ions to SLIM

Need to avoid ion losses upon injection of ions to SLIM devices

HPIF to SLIM interface

HPIF/IF to SLIM interfacefor larger reception area andbetter filed continuity to SLIM

ESI

SLIMExit Ion Funnel

MSy

z

Interface Ion Funnel

25 mm

ESI

Exit Ion Funnel

MSInterface Ion Funnel

25 mm

SLIM

4 ‐ 6 mm

Focusing Lens

New interface 

SLIM interface design and simulation

General conditions for RIF simulation (SIMION):Pressure: 4 torr N2 (Statistical Diffusion Simulation Model)Charged particle mass: m/z 50-2000

y

z

x

Rectangular Ion Funnel

Conventional Ion Funnel25 mm

25 mm

5 mm

5 mm

35 mm

DC + RF

DCGuard electrodes

Central rung electrodes

SLIM

Simulations

RF confinementConditions:

RF frequency: 750 kHz

RF amplitude: varied from 60 to 300 Vpp

Guard DC bias :4 V for SLIM0 V for RIF

DC gradient at central electrodes: 20 V/cm

ObservationsSimulation result shows most ions were transferred through rectangular electrodes to SLIM with a wide range of RF amplitudes.High RF amplitude results in better radial confinement essentially focusing high m/z ions.

RF = 60 Vpp

RF = 300 Vpp

y

z

m/z 350m/z 2050

Guard DC bias

Conditions:DC gradient: 20 V/cmRF: 750 kHz, 61.5 VppGuard DC bias:

SLIM: 5 VRIF: varied

ObservationsHigh guard DC bias leads ions dispersed in y directionLow guard DC bias leads ions dispersed in x direction

VRIF_Bias = ‐5 V

VRIF_Bias = +3 V

y

z

x

z

VRIF_Bias =  0 V

+3 V

0 V

‐5 V

Simulations

DC gradient along central rung electrodes

Conditions:RF: 750 kHz, 120 VppGuard DC bias:

5 V for SLIM1 V for RIF

DC gradient: varied

Observation:Less ion diffusion in radial direction was found with higher DC gradient along the RIF central electrodes.

June 19 20147

E = 5 V/cm

E = 10 V/cm

E = 20 V/cm

y

z

Simulations

Design and Fabrication

PCB-based RIF electrode designCentral (y) electrodes - RF + DC gradientGuard (x) electrodes - DC bias + DC gradient

25 mm5 mm

Central rung (y) electrodes

Guard (x) electrodes

0.0E+00

4.0E+04

8.0E+04

1.2E+05

30 80 130 180 230 280

Intensity

rf amplitude (Vpp)

622.17

1221.9

0.E+00

2.E+03

4.E+03

6.E+03

8.E+03

30 80 130 180 230 280

Intensity

rf amplitude (Vpp)

1821.72721.2(Ix10)

Initial RIF Characterization

RF confinementExperimental conditions

Pressure : 4 torrRF Freq.: 810 kHzRF Amplitude: variedGuard DC bias:

RIF In: 3.2 VRIF Out: 1.9 V

RIF DC gradient: 9 V/cm

Observations:m/z discrimination was observed for low RF amplitude between 60 and 110 Vppon RIFOptimal RF amplitude >110 Vpp is suggested for RIF

70 Vpp

110 Vpp

(a)

(b)

RIF In

RIF Out

Guard DC biasExperimental conditions

RF: 810 kHz, 160 VppPressure: 4 torrGuard DC bias:

varied Electrode dimensions

Inlet: 25.4 x 25.4 mmOutlet: 5 x 5 mm

RIF DC gradient: 9 V/cm

Observations:DC bias at inlet is less sensitive to the voltage change than that at outlet due to the different spacing of electrodesOptimal DC bias ranges of -10~+10 V for RIF inlet and +1~+3 V for outlet.

0%

20%

40%

60%

80%

100%

120%

‐40 ‐20 0 20 40 60

Ion Ab

unda

nce

dc bias (V)

90%

dispersed in X‐direction

dispersed in Y‐direction

0V

0%

20%

40%

60%

80%

100%

120%

‐5 0 5 10

Ion Ab

unda

nce

dc bias (V)

dispersed in X‐direction

dispersed in Y‐direction

1.9V90%

Initial RIF Characterization

(a)

(b)

0.06

0.08

0.1

0.12

0.14

0.16

0.18

0.2

0.22

0 2 4 6 8 10 12 14 16 18 20

Curren

t (nA

)

E (V/cm)

RIF DC gradientExperimental conditions

RF: Freq.: 750 kHzAmp.: 160 Vpp

Pressure : 4.1 torrDC gradient: VariedGuard dc bias:

Optimized based on the current measurement

ObservationRIF DC gradient >10 V/cm for optimal ion transmission for 3” RIF

9.3 V/cm

Initial RIF Characterization

RIF

Instrumental configuration used & ion optics design

4 torr 4 torr

9 V/cm

14 ‐20 V/cm

760 torr 1E‐8 torr

3” (76.2 mm) 15” (381 mm)

Initial RIF-SLIM Characterization

TOF‐MS

SLIM

0.0E+00

1.0E+04

2.0E+04

3.0E+04

4.0E+04

5.0E+04

6.0E+04

0 50 100 150 200 250 300 350

Intensity

RF amplitude (Vpp)

1521.82722.2 ( x50)

0.0E+00

5.0E+04

1.0E+05

1.5E+05

2.0E+05

2.5E+05

0 50 100 150 200 250 300 350

Intensity

RF amplitude (Vpp)

622.2 ( x2)1221.9

RF amplitudeConditions:

Guard DC bias :SLIM: 15 V forRIF In: 3.2 VRIF Out: 1.9 V

Central electrode DC gradient: SLIM: 14 V/cmRIF: 9.3 V/cm

RF frequency: RIF&SLIM: 810 kHz

RF amplitude: SLIM: variedRIF: 160 Vpp

120 Vpp

160 Vpp

m/z

m/z

Initial RIF-SLIM Characterization

(a)

(b)

140 Vpp

180 Vpp

SLIM DC gradientExp. Conditions

RF: Frequency: 810 kHzRIF amplitude: 160 VppSLIM amplitude: 200 Vpp

Pressure : 4 torrDC gradient:

RIF: 9.3 V/cmSLIM: Varied

Guard DC bias:Optimized based on the TIC measurement

Observationm/z discrimination was found for high m/z ions (1522-2422) with low DC gradient (>13 V/cm) on RIF-SLIM device

0.0E+00

4.0E+04

8.0E+04

1.2E+05

1.6E+05

0 5 10 15 20 25

322.2622.2922.011221.9

0.0E+00

1.0E+04

2.0E+04

3.0E+04

4.0E+04

0 5 10 15 20 25

1521.81821.62121.52422.3 (x50)

13 V/cmm/z

m/z

Initial RIF-SLIM Characterization

(a)

(b)

RIF-SLIM Performance

Sensitivity Exp. Condition

Pressure: RIF-SLIM: 4.00 torr

Guard DC bias, DC gradient& RF were optimized based on the characterization results.Solution electrosprayed:

Agilent ESI-L tune mixture

Observation:~2x intensity increase by RIF-SLIM

0.0

5.0x105

1.0x106

1.5x106

2.0x106

2.5x106

Inte

nsity

-2.5x106

-2.0x106

-1.5x106

-1.0x106

-5.0x105

0.0

322(2.3 X)

622(1.63 X)

922(1.9 X)

1222(2.5 X)

1522(1.5 X) 1822

(1.4 X)

IFT to SLIM interface

IFT/RIF to SLIM interface

0 1 2 3 4 5 6 7 8 9 10 110.0

2.0x107

4.0x107

6.0x107

TIC

Time (hour)

StabilityNo observable intensity decrease during the 11-hour stability test

Syringe pump stopped

Averaged from 0 to 11 hours

Agilent ESI‐L low concentration tuning mix

RIF-SLIM Performance

Set nESI voltageat 2.5 kV

0 500 1000 1500 2000 2500 30000.0

5.0x105

1.0x106

1.5x106

Inte

nsity

m/z

2122322

622

922

1222

1522

1822

Performance evaluation on RIF-SLIM

June 19 2014 17

200 4000.0

5.0x105

1.0x106

1.5x106

2.0x106

2.5x106

3.0x106

467, TAA8

411, TAA7

354, TAA6299,

TAA5

242, TAA4

Inte

nsity

m/z

186, TAA3

0 200 400 600 800 10000.0

5.0x104

1.0x105

1.5x105

2.0x105

(1) 354, [Bradykini+3H]3+

(2) 387, [Kimptide+2H]2+ (3) 433, [Angiotensin I+3H]3+

(4) 450, [Substance P+3H]3+

(5) 524, [Angiotensin II+2H]2+

(6) 530, [Bradykini+2H]2+

(7) 558, [Neurotensin+3H]3+

(8) 587, [Renin+3H]3+

(9) 674, [Substance P+2H]2+

(10) 712, [Melittin+4H]4+

(11) 769, [Fibrinopeptide A+2H]2+

(1)(4)

Inte

nsity

m/z

(2) (5)

(3)

(7)

(6) (8)(9) (10)

(11)

(a) (b)

(c) (d)

tetra‐n‐alkylammonium

600 800 1000 12000.0

2.0x105

4.0x105

6.0x105

8.0x105

1.0x106

1.2x106

1.4x106

1.6x106

1.8x106

Cytochrome c Deconvolution: 12253

+10+11+12

+13

+16

+14

+15+17

+18

+19

Inte

nsity

m/z

+20

600 800 1000 12000

1x105

2x105

3x105

4x105

5x105

+7+8+9

Inte

nsity

m/z

+14

+13

+12

+11

+10

UbiquitinDeconvolution: 8566

Conclusions

A Rectangular Ion Funnel (RIF) was designed, guided by ion simulations, including PCB-based circuit and electrode designs

The RIF and its interface with SLIM was characterized to determined the optimal operating parameters, including RF amplitude, Guard DC bias and central rung electrode DC gradients

The results of performance evaluation on RIF-SLIM indicated ~2x sensitivity increase, and displaying extended operation with high stability and without significant m/z discrimination over 300-2700 m/z range

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