Combining ion mobility spectrometry with mass
spectrometry for the analysis of complex samples:
the potential for environmental analysis
analytical.science@Loughborough
Centre for Analytical Science
Colin Creaser
RSC Joint Meeting,
3rd March 2017
Mobility of an ion in a drift tube in the presence of an electric field gradient and a buffer gas (e.g. He, N2 or air; 1-5 mbar or 1 bar)
vd = K . E [vd = ion velocity, E = electric field gradient, K = ion mobility]
(Low field) drift tube ion mobility spectrometry
Electric field
Aperture grid and
Faraday plate
Drift region
Ionization source
or transfer optics
Ion
gate
To detector or mass
spectrometer
Under low field conditions, ion mobility (K) is determined by:
K = (3q/16N) (2/kT) ½ (1/)
[N = buffer gas number density, T = temperature, q = ionic charge,
= reduced mass and = collision cross section]
Separation depends on ion charge and shape/size
K = (3q/16N) (2π/μkBT)½ (1/Ω)
RSC Joint Meeting,
3rd March 2017
Drift tube ion mobility spectrometry (DTIMS)
Ion mobility drift cell (Smiths Detection)
[Bramwell C, Colgrave M, Creaser C, Dennis R, Analyst, 2002, 127, 1467] RSC Joint Meeting,
3rd March 2017
4.2 cm drift tube
Resolution in ion mobility spectrometry
0
0.5
1
1.5
2
2.5
3
0 5 10 15 20
Drift time (ms)
Inte
ns
ity
(V
)
Figure 2: Nano-ESI/IMS spectrum of L-arginine at 100 C using
nitrogen drift gas.
[L-Arg+H]+
[(L-Arg)2+H]+ [Solvent]+
RP (FWHM) 32
Efficiency (N) 5800
[nano-ESI/IMS of L-arginine; 4.2 cm drift tube; N2 at atmospheric pressure]
[Bramwell C, Colgrave M, Creaser C, Dennis R, Analyst, 2002, 127, 1467] RSC Joint Meeting,
3rd March 2017
Ion mobility in high electric fields
K is dependent on the electric field strength
[Purves R W, Guevremont R, Anal. Chem. 1999, 71, 2346-2357]
Alpha coefficient – compound (ion) dependent
Mobility is dependent on electric field strength
Ion mobility in high and low electric fields
K (
Hig
h fie
ld)
K0 (
Low
fie
ld)
Increasing electric field strength
1
RSC Joint Meeting,
3rd March 2017
Factors affecting differential mobility in the gas phase
• Ion/buffer gas interactions (clustering/declustering)
• Frictional heating
• Structural/conformational change
• Dipole alignment
RSC Joint Meeting,
3rd March 2017
• Compensation field (CF) set to transmit ions of selected differential mobility
• Continuous ion beam (equivalent to quadrupole mass filter)
Field Asymmetric Waveform Ion Mobility Spectrometry
(FAIMS)/Differential mobility spectrometry (DMS)
Flow of
ions and
buffer gas
at ~1 bar
Dispersion
field (DF) and
Compensation
field (CF)
0 V
High field
Low field
Vhigh
Vlow
thigh
tlow
(a)
(b)
[Buryakov, I., et al., Int. J. Mass Spectrom. Ion Processes, 1993, 128, 143] RSC Joint Meeting,
3rd March 2017
FAIMS DF vs CF heat plot for 3-methylxanthine complexes
RSC Joint Meeting,
3rd March 2017 [Arthur et al., J. Am. Mass Spectrom., 2016, 27, 800-809 ]
Compensation field (CF; Td) Intensity vs CF (Td)
[(3-MX)4+Na]+ DF 323 Td
Dis
pe
rsio
n fie
ld (
DF,
Td
) [(3-MX)4+Na]+
Compensation field (CF; Td) Intensity vs CF (Td)
[(3-MX)4+Na]+ DF 320 Td
0
5000
10000
15000
20000
25000
30000
35000
40000
0 1 2 3 4
Sig
na
l In
ten
sit
y
Compensation Field /Td
2,4,6-TMA
N,N-DMT
ESI-FAIMS-MS of 2,4,6-trimethylaniline and N,N-dimethyl-m-toluidine (Dispersion field = 230 Td; electrode gap = 100 μm; 50 ng/ml)
Selected ion response
for m/z 136
[Smith R et al., Anal. Methods, 2013, 5, 3799] RSC Joint Meeting,
3rd March 2017
Applications of ion mobility spectrometry:
Stand-alone detection of explosives and chemical agents
RSC Joint Meeting,
3rd March 2017
Applications of ion mobility spectrometry:
International space station cabin air
RSC Joint Meeting,
3rd March 2017
Review: Marquez-Sillero et al, Ion-mobility spectrometry
for environmental analysis, TRAC, 2011, 30, 677-690]
Environmental applications of ion mobility spectrometry:
RSC Joint Meeting,
3rd March 2017
Ion mobility spectrometry configurations:
Ion mobility
device
Sample
extraction/
inlet system
Sample extraction/inlet systems: membrane inlet,
thermal desorption, SPE, SPME, GC, LC etc
RSC Joint Meeting,
3rd March 2017
Environmental applications of ion mobility spectrometry:
detection of BTEX by multicapillary GC/DTIMS
Drift
tube
[Sielemann, Baumbach et al. Field Anal. Chem. Technol., 2000, 4,157–169] RSC Joint Meeting,
3rd March 2017
UV lamp
[UV photoionization (positive ion), drift tube 6 or 12 x 1.5 cm (375 V/cm),
drift gas N2 at 200 ml/min, MCC SE-30 (70 cm)]
[Sielemann, Baumbach et al. Field Anal. Chem. Technol., 2000, 4,157–169]
Environmental applications of ion mobility spectrometry:
detection of BTEX by multicapillary GC/DTIMS
RSC Joint Meeting,
3rd March 2017
[Sielemann, Baumbach et al. Field Anal. Chem. Technol., 2000, 4,157–169]
Environmental applications of ion mobility spectrometry:
detection of BTEX by multicapillary GC/DTIMS
[UV photoionization (positive ion), drift tube 6 or 12 x 1.5 cm (375 V/cm),
drift gas N2 at 200 ml/min, MCC SE-30 (70 cm)]
RSC Joint Meeting,
3rd March 2017
Stand-alone ion mobility: environmental applications
• Transportability/field-based application of DTIMS/FAIMS
• Ease of use
• High sensitivity (<ppm)
• Rapid response (seconds – minutes)
• Limited dynamic range (1-2 orders of magnitude for drift tube IMS)
Threshold monitoring
• Low resolution (not suitable for complex mixtures)
Combined ion mobility-mass spectrometry
RSC Joint Meeting,
3rd March 2017
Ion mobility
device
Sample
extraction/
inlet system
RSC Joint Meeting,
3rd March 2017
MS: quadrupole, triple quadrupole, Q-trap,
time-of-flight, Q-TOF, Orbitrap
Mass
spectrometer
RSC Joint Meeting,
3rd March 2017
Drift tube ion mobility spectrometry (DTIMS)
Waters Synapt G2
Travelling wave (TWIMS) Static field
Agilent 6560
Excellims HRIMS
Tofwerk IMS-MS
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0.5 1 1.5 2 2.5 3 3.5
Drift time / ms
Inte
nsity / %
m/z 230 m/z 256 m/z 358 m/z 312 m/z 330 m/z 382
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0.5 1 1.5 2 2.5 3 3.5
Drift time / ms
Inte
nsity / %
m/z 230 m/z 256 m/z 358 m/z 312 m/z 330 m/z 382
m/z200 220 240 260 280 300 320 340 360 380 400
%
0
100358.10
330.12
252.02
230.04
217.09245.12
279.08
268.00
312.14
293.10
301.06
382.15
365.96
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
m/z
Ba
se
pe
ak in
tensity /
%
m/z200 220 240 260 280 300 320 340 360 380 400
%
0
100358.10
330.12
252.02
230.04
217.09245.12
279.08
268.00
312.14
293.10
301.06
382.15
365.96
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
m/z200 220 240 260 280 300 320 340 360 380 400
%
0
100358.10
330.12
252.02
230.04
217.09245.12
279.08
268.00
312.14
293.10
301.06
382.15
365.96
m/z200 220 240 260 280 300 320 340 360 380 400
%
0
100358.10
330.12
252.02
230.04
217.09245.12
279.08
268.00
312.14
293.10
301.06
382.15
365.96
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
+
N
O
OH
S
N
NH2
O
+ H
Cl
Cl
N
NH2
N
N
NH2
+
+ H
H
H
O
O
O
NH
+
+ H
H
H
O
O
O
NH
F
+
+ H
NCH3
O
H
NH
S
OO
N
+
+ HN
O
OS
N
NH2
O
+
+ H
m/z
Ba
se
pe
ak in
tensity /
%
(a)
(b)
ESI-IM(TWIMS)-MS analysis of protonated active
pharmaceutical ingredients
A. Lamivudine
B. Lamotrigine
C. Rosiglitazone
D. Desfluro Paroxetine
E. Paroxetine
F. Lamotrigine impurity
A B C D E F
Ion drift time (scan number)
% I
nte
nsity
[Howdle M D et al. Int. J. Mass Spectrom., 2010, 298, 72] RSC Joint Meeting,
3rd March 2017
E
A
C
B
F
D
A. Lamivudine
B. Lamotrigine
C. Rosiglitazone
D. Desfluro Paroxetine
E. Paroxetine
F. Lamotrigine impurity
Ion drift time (ms)
m/z
ESI-IM(TWIMS)-MS drift time vs m/z plot for protonated
active pharmaceutical ingredients
RSC Joint Meeting,
3rd March 2017
Environmental applications of ion mobility-mass
spectrometry: targeted analysis
RSC Joint Meeting,
3rd March 2017
Environmental applications of ion mobility-mass spectrometry: detection of
sulfonylurea herbicides in river water by ESI-DTIMS-quadrupole MS
[ESI (positive ion), drift tube 375 V/cm, drift gas N2 at 800 ml/min, river water sample
spiked with 25 ppm sulfometuron-methyl]
[Sielemann, Baumbach et al. Field Anal. Chem. Technol., 2000, 4,157–169]
Matrix ions Blank
[Sulfmeturon-methyl+H]+
(m/z 365)
RSC Joint Meeting,
3rd March 2017
[Sielemann, Baumbach et al. Field Anal. Chem. Technol., 2000, 4,157–169]
Selected ion monitoring for
[Sulfmeturon-methyl+H]+
(m/z 365)
Rapid analyte detection/identification based on m/z and drift time
[1000 IMS scans averaged over 50 s]
Environmental applications of ion mobility-mass spectrometry: detection of
sulfonylurea herbicides in river water by ESI-DTIMS-quadrupole MS
RSC Joint Meeting,
3rd March 2017
Mass spectrometer Electrospray ion source
FAIMS-MS: cylindrical electrodes (Thermo Scientific)
[Barnett et al., J Am Soc Mass Spectrom, 2007, 18, 1653–1663]
(electrode gap ~ 1-3 mm)
RSC Joint Meeting,
3rd March 2017
FAIMS-MS: planar electrodes
R.A. Miller, G.A. Eiceman, E.G. Nazarov, A.T. King, Sensors
and Actuators B 67, 300, 2000
AB SCIEX SelexION
(electrode gap ~ 0.5 mm)
RSC Joint Meeting,
3rd March 2017
Prototype Owlstone ultra-FAIMS chip mounted into chip cartridge located
behind spray shield in Jet Stream ESI source in front of transfer capillary
Prototype Owlstone ultra-FAIMS-Agilent 6230 TOF MS
[Smith et al. International Labmate, Jan/Feb 2014]
(electrode gap 0.1 mm)
RSC Joint Meeting,
3rd March 2017
[adapted from: B Ells et al., Anal. Chem. 2000, 72, 4555-4559]
[ESI (-ve ion, PE Sciex API 300), DV -3400/-3600 V (0.75 MHz), drift gas N2; 1 ppm]
Compensation voltage (V)
Inte
nsity (
cps x
10
-5)
HAA [M-H]-
(m/z)
LoD
(ppt)
Monochloro 93 28
Dichloro 127 10
Monobromo 137 18
Dibromo 217 14
Bromochloro 173 27
Environmental applications of ion mobility-mass spectrometry:
detection of haloacetic acids in water by ESI-FAIMS-quadrupole MS
RSC Joint Meeting,
3rd March 2017
[adapted from: B Ells et al., Anal. Chem. 2000, 72, 4555-4559]
Inte
nsity (
cps x
10
-3)
m/z m/z
Bromodichloroacetic acid
(m/z 207; 100 ppb )
RSC Joint Meeting,
3rd March 2017
Reducing chemical noise gives lower LOD and increased LDR
Environmental applications of ion mobility-mass spectrometry:
detection of haloacetic acids in water by ESI-FAIMS-quadrupole MS
Environmental applications of ion mobility-mass
spectrometry: non-targeted analysis
RSC Joint Meeting,
3rd March 2017
Heat plots for:
FAIMS-TOFMS (Owlstone ultra-FAIMS; CF vs m/z
at DF 240 Td)
and
TWIMS-TOFMS (Waters Synapt G2; Bin No. (drift
time) vs m/z)
[Urine extract after SPE extraction;
direct infusion; ESI]
RSC Joint Meeting,
3rd March 2017 [Arthur K. et al., Anal. Chem. 2017 (in press)]
Increased peak capacity
in screening/’omics’
applications
Acquisition of nested LC-DTIMS (TWIMS)-MS datasets:
(Metabolite profiling of saliva for biomarkers of physiological stress)
Data
processing
Mobile
phase
pumps
ESI-IM-TOFMS RP-UPLC
Inject
AM100629014.raw : 1
0 10 5
200
Retention Time (min)
Dri
ft T
ime
(bin
s)
AM100629014.raw : 1
A
B
[Malkar et al., Metabolomics, 2013, 9, 1192] RSC Joint Meeting,
3rd March 2017
10 min LC run = 600 TWIMS spectra = 128,000 TOF mass spectra
0
(m/z 100.07±0.02; δ-valerolactam (2-piperidone)
[Malkar et al., Metabolomics, 2013, 9, 1192]
m/z
m/z 100.0755
‘up-regulated’
in saliva after
exercise
RSC Joint Meeting,
3rd March 2017
Acquisition of nested LC-DTIMS (TWIMS)-MS datasets:
(Metabolite profiling of saliva for biomarkers of physiological stress)
Acquisition of nested LC-DTIMS (TWIMS)-MS datasets for
non-targeted analysis: analyte identification
• Retention time
• m/z (accurate mass)/Tandem mass spectrometry
(MS/MS)
• Ion mobility (drift time) → Collision cross section (CCS)
RSC Joint Meeting,
3rd March 2017
Ion mobility performance characteristics:
structural analysis
Measurement of collision cross section (Ω):
Directly from the Mason-Schamp equation (static field drift tube IMS)
Using calibrants (TWIMS and static field drift tube IMS)
K = (3q/16N) (2π/μkBT)½ (1/Ω)
RSC Joint Meeting,
3rd March 2017
Correlating an experimental CCS with CCS derived from
modelled/x-ray structures/library standards
Experimental CCS
for unknown
Compare CCSs
Modelled/x-ray structure
Calculated CCS
CCS value from
analysis of
standard
Library of CCS values
(e.g. metabolites)
RSC Joint Meeting,
3rd March 2017
RSC Joint Meeting,
3rd March 2017
Acquisition of nested LC-IM-qTOF-MS data for non-targeted analysis:
analyte identification in waste water sample by CCS measurement
LC retention time:10.72–10.75 min
[Stephan, S et al., Anal. Bioanal. Chem., 2016, 408, 6545-6555]
m/z
RSC Joint Meeting,
3rd March 2017
Acquisition of nested LC-IM-qTOF-MS data for non-targeted analysis:
analyte identification in waste water sample by CCS measurement
EIC for the [M+Na]+ adducts (m/z = 283.0140) of ifosfamid and cyclophosphamide
Ifosfamide (db CCS = 158.7 Å2) Cyclophosphamide (db CCS = 155.2 Å2)
[Stephan, S et al., Anal. Bioanal. Chem., 2016, 408, 6545-6555]
RSC Joint Meeting,
3rd March 2017
Acquisition of nested UHPLC-FAIMS-TOF-MS data for non-targeted
analysis of a urine extract
[Arthur K. et al., Anal. Chem. 2017 (DOI: 10.1021/acs.analchem.6b04315)]
RT 1.65-1.66 min
DF 240 Td
RSC Joint Meeting,
3rd March 2017
Acquisition of nested UHPLC-FAIMS-TOF-MS data for non-targeted
analysis of a urine extract
[Arthur K. et al., Anal. Chem. 2017 (DOI: 10.1021/acs.analchem.6b04315)]
Environmental analysis and ion mobility/mass spectrometry
• High level of orthogonality between ion mobility (differential mobility)
and m/z
• High sensitivity
• Rapid response (seconds – minutes)
• Structural analysis/analyte identification
• Resolution of isobaric/isomeric ions (reduced chemical noise)
Improved performance for targeted high throughput quantitative
analysis
Increased peak capacity for non-targeted (‘Omics’) applications
RSC Joint Meeting,
3rd March 2017
Acknowledgements
Loughborough: Kayleigh Arthur, Claire Bramwell, Med Benyezzar, Natali Budimir,
Michelle Colgrave, Caitlyn Da Costa, Neil Devenport, John Griffiths, Emma Harry, Mark
Howdle, Alex Hill, Gushinder Kaur-Atwal, Aditya Malkar, Rob Smith, James Stygall,
Katarzyna Szykula, Vicky Wright
Professor Gary Eiceman, Dr Jim Reynolds, Dr Steve Christie, Prof Paul Thomas, Dr Matt
Turner
Collaborators: Tony Bristow, Andy Poulton, Andy Ray, Dan Weston, Ian Wilson, Chris
Mussell, Gavin O’Connor, Elodie Champarnaud, Danielle Toutoungi, Billy Boyle, Lauren
Brown, Ashley Sage, Perdita Barran, Ewa Jurneczko, Alison Ashcroft, Tom Knapman,
Carles Bo, Fernando Castro-Gómez, Christine Eckers, Alice Laures, Jean-Claude Wolff
Tom Lynch, Sam Whitmarsh, Chrissie Wicking
Funders: BBSRC, EPSRC, EU, Agilent Technlogies, AstraZeneca, BP, GlaxoSmithKline,
Hope for Cancer, LGC, Loughborough University, Owlstone, Syngenta, Waters
RSC Joint Meeting,
3rd March 2017
