History

History of Tandem Ion Mobility Spectrometry At or Near Ambient Pressure

G.A. Eiceman, March 2014

 

The First Tandem IMS Instrument

Tandem IMS and the first demonstrations or tandem measurements date to the mid-1980s and were completed through a US Army contract to PCP, Inc..  The first instrument contained four sections in the drift tube with traditional time of flight design or line of sight geometry.  An ion source and reaction region were joined to three drift regions separated by three ion shutters and an ion source volume.1,2  In this tandem drift tube design (Figure 1), ions formed in the source region were injected using a first ion shutter into a drift region where ions swarms were separated in drift time.  At the end of this first drift region, a second ion shutter was located and synchronized to the first shutter and control of delay

 

Schematic of the first Tandem Ion Mobility spectrometer

Schematic of the first Tandem Ion Mobility spectrometer

Figure 1. Schematic of the first Tandem Ion Mobility spectrometer from PCP Inc. (A) in a configuration with a photodischarge lamp.  Three ion shutters were employed to isolate ions of certain mobility for subsequent chemical reactions and then a final section for ion mobility analysis of products. could allow ions from only a portion of drift time to be isolated and passed to a second drift region.  In this next drift region, ions could be fragmented by laser irradiation or vapors added to promote selective reactions and additional analytical selectivity.  Ions formed in this second region were subsequently characterized in a third drift region which was also preceded with an ion shutter.  The open drift ring structure in this first tandem IMS, much as the original Beta VI design, permitted uncontrolled movement of sample neutrals between mobility regions.  This created ion molecule reactions in the drift regions and these complicated interpretation of spectra and results.

Tandem Ion Mobility Spectrometers in Recent Years

Kinetic IMS.  Studies on the lifetimes of gas ions in air at ambient pressure using drift tubes with mobility spectrometers were advanced with a dual shutter IMS/MS,3,4 where a drift region was used to isolate a particular ion peak by mobility selection with a second ion shutter, in a manner known with boxcar integrators.  The selected ion was allowed into are relatively small drift region between the second shutter and the entrance to a quadrupole mass spectrometer.  There was time enough in this short region for ion decomposition to be observed and for rate constants to be measured.  In 2010 to 2012, an IMS/IMS instrument was built with a Faraday plate detector particularly for kinetic measurements5 and a schematic of this drift tube is shown in Figure 2. This instrument is in active use for determining the lifetime of ions from explosives in air.6

. A tandem IMS/IMS instrument Figure 2. A tandem IMS/IMS instrument with a Faraday plate detector and dual shutter operation designed, built, and operated at New Mexico State University.

Low pressure IMS/IMS. An IMS/IMS instrument for use at 3 torr in helium atmosphere of helium has also been described in combination with a mass spectrometer7 to improve analytical performance in IM MS methods.  The separating efficiency was indeed improved by a factor of 8 with two-dimensional IMS for mixtures of tryptic peptides.  The drift tubes were 100 cm long.

 

Tandem Mobility Spectrometers with Mixed Principles of Mobility

A tandem mobility analyzer combining DMS with IMS was designed around a micro-fabricated DMS analyzer and two miniaturized IMS detectors arranged in an orthogonal configuration (Figure 3), and both positive and negative ions could be determined simultaneously by high field and low field measurements.8,9  Ions were passed at specific compensation voltage through a DMS section and were drawn into drift tubes of appropriate polarity placed in a twin drift tube geometry and build from conventional mobility principles.

A DMS/IMS2 built at NMSU in a program jointly with Hamilton Sundstrand and Sionex, Inc as part of a Homeland Security funded effort

Figure 3. A DMS/IMS2 built at NMSU in a program jointly with Hamilton Sundstrand and Sionex, Inc as part of a Homeland Security funded effort.

The ion shutters initially were micro-machined design and the entire drift tube was 1 cm long; the DMS was a micro-fabricated design developed at NMSU under Draper Laboratory funding.  An anticipated benefit with a DMS/IMS measurement was that each ion would be characterized on principles of K versus ΔK and orthogonal character would be introduced into a mobility measurement.  As shown in Figure 3, there was a pattern in drift time and compensation voltage and this trend was observed over several classes of chemicals and homologous series.  As a consequence, if one parameter was known, with a reasonable boundaries, the other could be predicted and there was little orthogonal nature to these measurements.

Plot of compensation voltage from DMS first stage and drift time from IMS second stage

Figure 4. Plot of compensation voltage from DMS first stage and drift time from IMS second stage in small DMS IMS analyzer for characterization of protonated monomers and proton bound dimers of ketones in air at ambient pressure.  Sadly, this work has not been published, only presented though the years.  (In this DMS, waveforms were applied so that ions with large positive ΔK appeared with positive CV).

Approximately 20 DMS/IMS instrument were produced commercially by Sionex, Inc. from 2005 to 2010 and little has been disclosed in open literature.

 

A somewhat different result to these was obtained with a slightly larger embodiment of a field asymmetric IMS-IMS-tandem MS instrument where ions were moved at reduced pressure in non-clustering gases.  A combination of CV and drift time was suggestive of some orthogonality between drift time and compensation voltage although this was not quantitatively determined.10,11  This instrument, shown in Figure 4 and findings from FAIMS IMS measurements are shown in Figure 5.  There is clearly some orthogonal character to the measurement when the mobility instrument is significantly different gas atmosphere.  There was no apportionment of differences between K and ΔK.

Schematic of the ESI-FAIMS/IMS/Q-TOF MS instrumentation

Figure 5. Schematic of the ESI-FAIMS/IMS/Q-TOF MS instrumentation.

 

 

 

 

Dispersions of distinct peptide spots in the FAIMS/MS (a) and FAIMS/IMS (b) planes confirming the orthogonality of FAIMS separations to MS and IMS.

Figure 6. Dispersions of distinct peptide spots in the FAIMS/MS (a) and FAIMS/IMS (b) planes confirming the orthogonality of FAIMS separations

to MS and IMS.

 

Tandem Mobility Spectrometry as IMS/FAIMS

The DMS IMS design can be inverted with IMS drift tube placed before a DMS analyzer and a dual shutter IMS can be a success inlet for FAIMS by isolating an ion swarm for subsequent field dependent characterization (Figure 6).  There is a complication with timing where the scanning speed of a DMS is 0.5 to 2 Hz and this can be seen as a poor match to the repetition rate of an IMS drift tube (10 to 30 Hz).  Nonetheless, the IMS will provide a stream of ions with pulses established in a boxcar integrator operation with dual shutters, not unlike an IMS/MS with dual shutters dating to the earliest commercial IMS instruments of 1970.

A tandem mobility spectrometer where an IMS drift tube preceded a FAIMS (high field mobility measurement) and finally a mass analyzer for detector

Figure 7. A tandem mobility spectrometer where an IMS drift tube preceded a FAIMS (high field mobility measurement) and finally a mass analyzer for detector.12

 

A successful combination of a drift tube with a FAIMS-Ion trap mass spectrometer with MSn capability was demonstated12 and a significant result was the isolation in the drift tube of one peak for tyrosine-tryptophan-glycine which when introduced into the FAIMS was resolved into two conformer peaks.

 

 

 

Tandem Differential Mobility Spectrometry

Although DMS/IMS measurements described above had little orthogonal character, owing to similarities in K and ΔK, orthogonality in tandem IMS methods could be added through the introduction of ion-molecule reactions mobility drift tubes.  A first embodiment of DMS/DMS (Figure 8) was attached to a mass spectrometer and results in 201013 suggested that steering of ions was possible (Figure 9).

 

 First DMS/DMS description at Pittcon 2010 which proved that ions could be steered in a tandem instrument  Results from steering ions in a tandem DMS. Pittcon 2010
Figure 8. First DMS/DMS description at Pittcon 2010 which proved that ions could be steered in a tandem instrument. Figure 9. Results from steering ions in a tandem DMS. Pittcon 2010

That is, two DMS analyzers couldbe joined and ions flowed between these and into a mass spectrometer.  Separate electronic control for each drift tube permitted several modes of operation including all ion pass, compensation voltage (CV) scanning, and ion selection over a narrow CV range.  Orthogonality could be added to a tandem DMS measurement if reagent could be added in the gap between the two drift tubes.  This was attempted in 2011 with the same DMS/DMS/MS instrument (Figure 10).14  The combination of supersonic expansion and ion heating of fields in the interface between DMS/DMS and mass spectrometer yielded ion patterns which proved to be too complex for interpretation (Figure 11) and while some evidence of chemical modification of ΔK in a second DMS was observed, the findings were not persuasive.  A tandem mobility spectrometer with two sequential (DMS) drift tubes and

 First effort to introduce a reagent in a tandem DMS/DMS measurement. PIttCon 2012  Complex pattern of ion populations with DMS/DMS/MS instrument frustrated assessment of chemical modification of ions.
Figure 10. First effort to introduce a reagent in a tandem DMS/DMS measurement. PIttCon 2012 Figure 11. Complex pattern of ion populations with DMS/DMS/MS instrument frustrated assessment of chemical modification of ions.

Faraday detectors at ambient pressure (Figure 12) was designed to accept a reagent gas15 and several modes of operation could be applied to the drift tubes allowing a range of analytical measurements analogous to tandem mass spectrometry.  In these studies, ions between mobility regions were clustered, stripped of charge chemically, or entered into a new supporting gas atmosphere rather than fragmented.  In one example, the benefit of DMS/DMS was in the resolution of proton bound dimers of organophosphates- ions for both chemicals appeared near 0 V in the compensation voltage scale of DMS1 and exhibited distinctive spectra in DMS2 after entering into an iso-propanol rich gas atmosphere (Figure 13).

Schematics of (a) DMS/DMS system with (b) enlarge graphic of DMS/DMS analyzer.

Figure 12. Schematics of (a) DMS/DMS system with (b) enlarge graphic of DMS/DMS analyzer.

 

 

 

 

 

 

 

DMS2 spectra of (a) DMMP and (b) TBP at SVDMS1= 700V and CVDMS1=0V with 1% isopropanol introduced between the DMS analyzers

Figure 13. DMS2 spectra of (a) DMMP and (b) TBP at SVDMS1= 700V and CVDMS1=0V with 1% isopropanol introduced between the DMS analyzers (Fig. 10)

 

 

 

 

 

 

 

In 2013, studies were completed that demonstrated that a tandem DMS could provide selectivity in the characteristic dependences of ions in strong electric fields and that response could be as low as 100 ms, with most time used in computer overhead.  When DMS1 and DMS2 were set to particular combinations of SV and CV and used as ion filters, ions passing only with the characteristic dispersion curves which matched the criteria of both CV1:SV1 and CV2:SV2 would pass through the tandem DMS instrument.17-20  This is shown in Figures 13 and 14.  Although a gas chromatograph was employed as the inlet in these experiments, the intention was to removed competitive charge exchange in the ion source as a complication in interpretation of response.

Composite dispersion plot of DMMP, heptanol-1 and cyclohexanone in purified air at 45°C

Figure 14. Composite dispersion plot of DMMP, heptanol-1 and cyclohexanone in purified air at 45°C.

 

 

 

 

 

 

 

 

Extracted ion chromatograms for mixture of DMMP, heptanol-1 and cyclohexanoneFigure 15. Extracted ion chromatograms for mixture of DMMP, heptanol-1 and cyclohexanone: a) XIC with DMS1 in all pass mode and SVDMS2=500V and CVDMS2=-0.4 V  b) XIC with SVDMS1=500V, CVDMS2= -0.4V and SVDMS1=1000V, CVDMS1=-0.8V; c) XIC with SVDMS1= 600V, CVDMS1=0V and SVDMS2=1400V, CVDMS2 =2.2V; d) XIC with SVDMS1=700V, CVDMS1=0V and SVDMS2=1500V, CVDMS2=4.0V

 

 

 

 

LITERATURE CITED

1. Stimac, R.M.; Wernlund, R.F.; Cohen, M.J.; Lubman, D.M.; Harden, C.S., Initial studies on the operation and performance of the tandem ion mobility spectrometer,  Pittcon. 1985 New Orleans, LA, March 1985.

2. Stimac, R.M.; Cohen, M.J.; Wernlund, R.F., Tandem ion mobility spectrometer for chemical agent detection, monitoring and alarm, Contractor Report on CRDEC Contract DAAK11 84 C 0017, PCP, Inc., West Palm Beach, FL, May 1985, AD B093495.

3. Ewing, R.G., Kinetic Decomposition of Proton Bound Dimer Ions with Substittued Amines in Ion Mobility Spectrometry, Dissertation, New Mexico State University, Dec. 1996.

4. Ewing, R.E.; Eiceman, G.A.; Harden, C.S.; Stone, J.A., The kinetics of the decompositions of the proton bound dimers of 1,4-dimethylpyridine and dimethyl methylphosphonate from atmospheric pressure ion mobility spectra, Int. J. Mass Spectrom. 2006, 76-85, 255-256.

5. An, X. .; Stone, J.A.; Eiceman, G.A.,  Gas phase fragmentation of protonated esters in air at ambient pressure through ion heating by electric field in differential mobility spectrometry and by thermal bath in Ion Mobility Spectrometry, Int. J. Mass Spectrom. 2011, 303(2-3), 181-190.

6. Rajapakse, R.M.M.Y.; Stone, J.A.; Eiceman, G.A.; Design and Performance of Ion Mobility Spectrometer for Kinetic Studies of Ion Decomposition in Air at Ambient Pressure, 2014, accepted J. Phys. Chem.

7. Valentinea, S.J.; Kurulugamaa,R.T.; Bohrera,B.C.; Merenblooma,S.I.;Sowell, R.A.; Mechref, Y.; Clemmer, D.E.Developing IMS–IMS–MS for rapid characterization of abundant proteins in human plasma, Int. J. Mass Spectrom. 2009, 283, 149–160

8. White, C. R., Characterization of tandem DMS-IMS2 and determination of orthogonality between the mobility coefficient (K) and the differential mobility coefficient (ΔK), M.S Thesis, New Mexico State University, Las Cruces, NM May 2006.

9. Eiceman, G.A.; Schmidt, H.; Rodriguez, J.E.; White, C.R.; Nazarov, E.G.; Krylov, E.V.;  Miller, R.A.; Bowers, M.; Burchfield, D.; Niu, B.; Smith, E.; Leigh, N.; Characterization of positive and negative ions simultaneously through measures of K and ΔK by tandem DMS-IMS, ISIMS 2005, Château de Maffliers, France

10. Tang, K.; Li, F.; Shvartsburg, A. A.; Strittmater, E. F.; Smith, R. D. Anal. Chem. 2005, 77, 6381−6388.

11. Shvartsburg, A. A.; Li, F.; Tang, K.; Smith, R. D. Anal. Chem. 2006, 78, 3304−3315.

12. Pollard, M.J.; Hilton, C.K.; Li, H.; Kaplan, K.; Yost, R.A.; Hill, H.H. , Ion mobility Spectrometer-Field Asymmetric Ion Mobility Spectrometer-Mass Spectrometry, Int. J. Ion Mobility Spectrom. 2011, 14 (1), 15-22.

13. Ion Preparation before Differential Mobility Spectrometry including DMS/DMS Analyzers, PittCon2010, Orlando Fl.

14. Tandem Differential Mobility Spectrometers with Chemical Orthogonality Through Cluster Reactions and Electric Field Fragmentation, PittCon2011, Atlanta GA

15. M. Menlyadiev, J.A. Stone, G.A. Eiceman, Tandem ion mobility measurements with chemical modification of ions selected by compensation voltage in differential mobility spectrometry/differential mobility spectrometry instrument, International Journal of Ion Mobility Spectrometry 2012, 15(3), 123-130

16. Eiceman and M. Menlyadiev DMS/DMS: A Powerful System for Gas Phase Reaction Studies and Enhanced Ion Identification, 21st International Conference for Ion Mobility Spectrometry July 22-26, 2012 Orlando, FL.

17. G.A. Eiceman and M. Menlyadiev, Tandem differential mobility spectrometer: an ionization detector for gas chromatography with high speed, selective, small size and low cost,  37th International Symposium on Capillary Chromatography May 12-16, 2013, Renaissance Palm Springs, Palm Springs, CA USA

18. Exploration of Tandem Mobility Spectrometry concepts and practices at ambient pressure, 22nd International Conference for Ion Mobility Spectrometry July 20-26, Boppard, Germany 2013.

19. Tandem Configurations of Ion Mobility Spectrometers at Ambient Pressure, concepts and practices, British Mass Spectrometry Society, September 9-11, 2013, Eastborne, England

20. Menlyadiev, M.; Eiceman, G.A. Tandem Differential Mobility Spectrometry in Purified Air for High Speed Vapor Detection, Analyt. Chem. 2014, dx.doi.org/10.1021/ac4031169.