62nd ASMS Conference June 15 -19, 2014 Baltimore, Maryland
Mass Selective Axial Ejection in a Low
Pressure Linear Ion Trap in the Presence of
Nonlinear RF Fields
Mircea Guna
June 18th, 2014
QTRAP® Technology. Mass Selective Axial Ejection
Linear Ion Trap on a Triple Quad backbone
The axial ejection linear ion trap
- operates in the low 10–5 Torr presurre regime
- ions emerge from the end of the device.
QqQlinear ion trap geometry combines all of the features of a
conventional triple quadrupole mass spectrometer and a
linear ion trap.
Hager JW, Le Blanc JCY (2003) Rapid Commun Mass Spectrom 17:1056–1064
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QTRAP® 6500 system à high sensitivity
QqQ/LIT
Enhanced Product Ion Scan (EPI) Diagram
– precursor ion selection in Q1
– beam type fragmentation in the collision cell Q2
– trap products and the un-fragmented precursor
ions in Q3
– analytical scan - Linear Ion Trap mass scan
QTRAP® 6500/5500 System Ion Path
Q3 LIT
Curtain
Plate
Orifice
Pulse Gas
Valve
Q2
MS/MS
Q0
QJet® 2
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Q1-RF/DC filter
Multi Target Screening
- A predefined list of compounds is looked for in a Multiple Reaction
Monitoring (MRM) experiment.
- Once a compound is detected above a defined threshold an EPI
scan is collected and compared against a library.
- Dynamic exclusion of compounds where MS/MS spectra are already
acquired allows the data collection of co-eluting compounds.
Required Mass accuracy:
0.1 Da or better.
Experimental Sequence of a Multi Target Screening
(MTS) approach
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Ion Trap Mass Spectral Quality and Space Charge
Space charge causes loss of
– mass assignment
– peak shape
– relative intensities
More sensitive MS/MS systems will exacerbate this issue as we strive to
lower our overall limits of detection.
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Effects of Space Charge – QTRAP ® 6500.
DFT turned OFF.
X 30 ions
∆ m > 0.4 Da
Zoom
Zoom
X 30 ions
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Methods to Mitigate Space Charge Effects in RF Ion Traps
Goal is to maintain spectral fidelity with increasing ion population.
Can use:
- ‘dynamic fill time‘ (DFT) or Automated Gain Control, but increased cycle times
thus loss of chromatographic resolution
- Tandem ions traps, amenable for large mass range scans (Guna and Londry,
Anal. Chem. 2011, 83, 6363-6367)
- Internal Calibration (Remes and Schwartz ASMS 2012 MP30-706)
- Nonlinear Fields
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Nonlinear RF Fields in Ion Traps.
- 3D Ion Traps – ejection slit, stretched or asymmetric
configurations (Stafford, Syka, Franzen, Wang, Cooks)
- Radial Ejection LIT - slit, stretched, non-hyperbolic rods
(rectilinear), asymmetric applied RF fields (Schwartz,
Cooks, Welsh)
- Axial Ejection LIT – round rods, asymmetric rods
(Hager, Douglas)
- Toroidal IT – curvature (Austin, Lammert)
Practical Aspects of Ion Trap Mass Spectrometry Series. CRC Press.
Editors Raymond E. March, John Francis James Todd
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Mass Selective Axial Ejection. QTRAP® Technology
- mass-selective axial ejection (MSAE) of ions takes advantage of the RF
fringing fields, at the end of the linear quadrupole, to convert radial ion
excitation into axial ejection.
- the higher the radial amplitude the stronger the axial force experienced
by the ions.
Dehmelt approx.:
E z, quad
RF
x = X +δx
∂f m Ω 2 2
qx X 2 + Y 2
=
∂z 8e
(
)
ion radial amplitude
fringing field
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Londry and Hager, JASMS, 2003,14, 1130-1147
Nonlinear High Capacity Linear Ion Trap (NHCT)
Research Prototype.
Schematic of the Electrical/Mechanical set-up of the NHCT.
The RF on the T-electrodes was generated by a signal generator,
phase-locked to the main RF and amplified by an amplifier.
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Nonlinear High Capacity Ion Trap. RF fields.
RF Potential due to the Auxiliary Electrodes
-6
500
450
400
350
300
250
200
150
100
50
0
-4
-2 -50 0
2
4
Distance from the quadrupole axis [mm]
y = 0.0002x6 + 1E-06x5 - 0.0117x4 - 2E-05x3 + 0.0104x2 - 5E-05x + 2.3137
2.5
2
0V
50 Vp-p
1.5
Potential [V]
Potential [V]
RF Voltage in Excitation Plane. Main RF voltage
884 Vp-p
Z 2.4mm from the Exit Lens
1
0.5
0
6
-6
-4
-2
0
-0.5
2
Distance from the quadrupole axis [mm]
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4
6
RF Electric Field. z 2.4mm.
Electric Field due to Auxiliary Electrodes
y = 6E-08x6 - 0.0003x5 - 3E-06x4 + 0.0096x3 + 3E-05x2 - 0.0047x - 3E-06
0.4
50
0.3
40
30
Electric Field [V/mm]
20
10
0 Vp-p
0
-6
-4
-2
-10
0
2
-20
-30
-40
-50
Distance from the quadrupole axis [mm]
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4
6
50 V p-p
Electric Field [V/mm]
0.2
-6
0.1
0
-4
-2
0
2
-0.1
-0.2
-0.3
-0.4
Distance from the quadrupole axis [mm]
4
6
Ion Motion Frequency vs. Auxiliary RF
Experimental Measured m/z
195.6
345000
195.4
343000
f [Hz]
0 Vp-p
339000
337000
335000
333000
0
1
2
Amplitude [mm]
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3
mz/ [Da]
195.2
341000
195
25 Vp-p
194.8
50 Vp-p
194.6
75 V p-p
194.4
0
20
40
60
Auxiliary RF [Vp-p]
80
100
Effects of Space Charge – QTRAP ® 6500.
DFT turned OFF.
X 30 ions
∆ m > 0.4 Da
Zoom
Zoom
X 30 ions
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Effects of Space Charge – NHCT. DFT turned OFF.
X 30 ions
∆ m < 0.1 Da
Zoom
Zoom
X 30 ions
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QTRAP ® 6500 vs NHCT
QTrap ® 6500
NHCT
100
100
90
90
80
80
70
70
60
60
50
50
40
40
30
30
20
20
10
10
0
0
361
363
365
367
369
371
361
363
365
367
369
- x30 Ions
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371
Mass Accuracy is retained for large populations of ions.
NHCT
7k ions
70k ions
700k ions
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Intra-Scan Dynamic Range. NHCT
7k ions
70k ions
700k ions
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Mass Shift vs Total Number of ions in the NHCT
Mass Shift of the 213Da peak vs. Total Number of Ions present in the trap. RF
Voltage on the T electrodes was 60 Vp-p
0.25
0.2
Mass Shift [DA]
0.15
0.1
60 V
0.05
0
0
-0.05
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250000
500000
750000
1000000
Total Number of Ions [counts]
1250000
1500000
Influence of the Auxiliary Electrodes RF voltage on Mass
Shift. Scan Rate 10 kDa/s. 4cm long NHCT.
Mass Shift of the 213Da peak vs. Total Number of Ions present in the trap and
RF Voltage on the T electrodes
0.25
0.2
Mass Shift [DA]
0.15
0V
20 V
0.1
40 V
60 V
0.05
QTRAP 6500
0
0
-0.05
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250000
500000
750000
1000000
Total Number of Ions [counts]
1250000
1500000
Searching for impurities. Fendiline & Flusilazol mixture
F
F
Fendiline:Flusilazol 100,000:1
316.206 Th:316.1076 Th
F
F
F
Zoom
F
F
F
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F
SUMMARY
Higher order fields increase the space charge immunity of
the trap by at least a factor of x10.
Applicable to all of the applications that use trap scans
(e.g., MIDAS Workflows)
Improvements, at large ion populations, in:
– Mass assignment and Resolution
– Spectral Quality
– Intra-scan dynamic range
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Acknowledgements
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Designers
Scientists
Pablo Dominguez
Jim Hager
John Vandermey
Larry Campbell
Matthew Romaschin
Frank Londry
© 2014 AB SCIEX
Trademarks/Licensing
For Research Use Only. Not for use in diagnostic procedures.
© 2014 AB SCIEX. The trademarks mentioned herein are
the property of AB Sciex Pte. Ltd. or their respective owners.
AB SCIEX™ is being used under license. All rights reserved.
Information subject to change without notice.
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Questions and Answers