Search tips
Search criteria 


Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Anal Chem. Author manuscript; available in PMC 2010 September 24.
Published in final edited form as:
PMCID: PMC2945891

High-Resolution Differential Ion Mobility Separations Using Helium-Rich Gases


Analyses of complex mixtures and characterization of ions increasingly involve gas-phase separations by ion mobility spectrometry (IMS) and particularly differential or field asymmetric waveform IMS (FAIMS) based on the difference of ion mobility in strong and weak electric fields. The key advantage of FAIMS is substantial orthogonality to mass spectrometry (MS), which makes FAIMS/MS hybrid a powerful analytical platform of broad utility. However, the potential of FAIMS has been constrained by limited resolution. Here, we report that the use of gas mixtures comprising up to 75% He dramatically increases the FAIMS separation capability, with the resolving power for peptides and peak capacity for protein digests reaching and exceeding 100. The resolution gains extend to small molecules, where previously unresolved isomers can now be separated. These performance levels open major new applications of FAIMS in proteomic and other biomolecular analyses.

Mass spectrometry (MS) preceded by separations has become preeminent for the identification and quantification of various chemical species.1 Separations used increasingly include ion mobility spectrometry (IMS), where ions are sorted based on their gas-phase transport in electric field.212 In conventional (drift-tube2 or traveling-wave8) IMS, ions are dispersed by the absolute mobility, K. The field intensity (E) is normally low, and K is governed2,3 primarily by the ion-molecule collision cross section, Ω. This quantity may be computed for any ion geometry, which enables characterization of the ion structure. The mobility of ions in gases depends2,4 on E, which is exploited in differential or field asymmetric waveform IMS4,9,10 (FAIMS) to separate ions by the differences of K values at high and low E. The separation proceeds in a periodic asymmetric field E(t) of some amplitude (ED) in a gap between two electrodes. Ions, carried through the gap by gas flow, drift toward an electrode and are neutralized on contact. A fixed “compensation field” (EC) superposed on E(t) can offset this drift for a particular species and let it transit the gap, while others are lost. Scanning EC provides a spectrum of species entering the gap. While no means to extract ion structures from FAIMS data has yet been devised, the distinctive outcomes of FAIMS and conventional IMS separations are evident from 2-D FAIMS/IMS measurements that also reveal the geometries of species resolved by FAIMS.11,12

Since the emergence of FAIMS, its resolving power R, defined as EC/(peak width at half-maximum), has been restricted9,11 to ~10–15 vs ~100–200 for drift-tube IMS.1317 A new planar FAIMS device with the ion residence time of ~0.2 s has recently increased1820 R to ~30–60 for typical species. Despite a lower R, FAIMS often separates isomers or isobars better than conventional IMS and provides greater peak capacity in conjunction with MS,11,18,20 since the K(E) derivative is correlated with the ion mass (and mass/charge) weaker than K. Still, the modest R achievable has limited the FAIMS utility.

IMS has utilized various gases, commonly He or N2. Conventional IMS using He allows accurate mobility calculations for structural elucidation, but R is independent of the gas composition.21 In FAIMS, R is sensitive to the gas properties4,9 and improves as the fraction of He in He/N2 mixtures increases to 50% (v/v). With the planar FAIMS geometry, the gain generally comes from both broader separation space (greater distance between the peaks) and narrowing of the peaks in lighter gases where ions are more mobile.4,20 Larger He fractions have not been employed in FAIMS, primarily to avoid electrical breakdown in the gap. For a typical9,1820 gap width of 2 mm and ED = 20 kV/cm, breakdown for dc field at ambient pressure and temperature occurs for He content over ~65%.

Here, we report use of He/N2 mixtures with up to 75% He for ED ~ 21 kV/cm. This is feasible because the breakdown threshold in a gas increases for rf fields of high frequency w, when ion oscillations are well within the gap, a criterion met in FAIMS.4 For present w = 750 kHz, we observe breakdown at ~80% He, permitting stable operation up to ~75%. We have found that the higher He content dramatically increases resolving power (e.g., to ~100 and more for peptides) and allows separation of previously unresolved species.


Experiments employed a previously described18,20 planar FAIMS unit with 1.88 mm gap width, driven by a 2:1 bisinusoidal4,9 waveform with the 750 kHz frequency and nominal peak voltage of DV = 4 kV. The DV read-back was ~4.05 kV (creating ED = 21.5 kV/cm) vs ~3.97 kV (ED= 21.1 kV/cm) previously,20 leading to slightly higher EC and, thus, R values for peptides at the same He fractions. The unit was coupled to an LTQ ion trap MS (Thermo Scientific, Waltham, MA) with an electro-dynamic ion funnel interface in front.22 The FAIMS outlet was ~2.5 mm from the MS inlet capillary held at 30–50 °C (as ion desolvation after FAIMS is redundant). The inlet, FAIMS body, and the curtain plate at the FAIMS entrance were biased at ~120–160 V, ~160–190 V, and 1 kV to the ground, respectively. Ions were produced by electrospray ionization (ESI) in the positive mode. The emitter voltage was 1.5–2.3 kV above the curtain plate, lower at higher He content to avoid electrical discharge and improve the signal stability. The He/N2 mixtures at room temperature were formulated using digital flow meters with feedback control (MKS Instruments, Andover, MA), filtered by a LC/MS gas purifier for N2 (Agilent Technologies, Santa Clara, CA), and flowed to the FAIMS unit at 1.8 L/min (for peptides and digests) or 2.3 L/min (for amino acids). Under these conditions, ions traversed the gap in 0.1–0.2 s. The amino acid and peptide standards were dissolved in 50/49/1 water/methanol/acetic acid. The tryptic digest of BSA was prepared as usual, reduced, alkylated, and reconstituted in the 50/49.8/0.2 water/acetonitrile/formic acid. Sample solutions were infused to the emitter at 0.2–0.5 μL/min. The MS resolution was set to “normal” or (to assign the charge states of features by the isotope pattern) “zoom”. The ion accumulation time in the trap was ~0.2–0.5 s. The FAIMS scan rate was 1–2.5 V/(cm × min).

We caution that the turbomolecular pumps of LTQ MS lose efficiency at greater He content in the gas, and the pressures measured by the ion and convectron gauges increase from, respectively, 1 × 10−5 and 1.3 Torr at 0% He to 1.7 × 10−5 and 2.0 Torr at 75% He. While we operated in that regime for an extended time, it is above the pressure range normal for the present and other common commercial API/MS platforms that are not designed for aspiration of He-rich mixtures from the inlet. Elevated pressure in the MS manifold may affect the accuracy, resolution, and/or sensitivity of MS analyses and cause hardware failures.


A stringent test of IMS resolution is separating the isomeric leucine (L) and isoleucine (I) amino acids. In conventional IMS, the protonated cations are fully resolved at the highest R ~ 150 reached in drift-tube IMS15 but not by the commercially available traveling-wave IMS.23 Previously, FAIMS could barely resolve either L and I cations18 or deprotonated anions:24 for cations, a minimal separation emerged only at 50% He. We find that higher He fractions significantly improve the resolution: r, (peak spacing)/(peak width), changes from 1.0 at 50% to 3.4 at 73% He, providing baseline separation at ~70% He (Figure 1). The gain is mainly due to the peak spacing increasing by 2.7 times (from 1.8 V/cm at 50% to 4.9 V/cm at 73% He), but narrowing of the peaks with increasing K values also contributes. The peak heights reflect the 1:1 L/I ratio in the sample up to ~65% He but deviate in either direction beyond that. The main reasons are that higher He fractions (i) destabilize the ESI source, increasing the temporal fluctuations of ion flux and (ii) reduce ion transmission through the FAIMS gap and, thus, the detected signal, worsening the ion count statistics.

Figure 1
Mass-selected FAIMS spectra for the 1:1 Leu/IIe mixture (solid lines) in He/N2 with ≤50% He (left) and ≥50% He (right). The values of resolution r are given for separated isomers. Pure Leu or IIe yield single peaks matching “L” ...

The EC values for both isomers initially become more negative with added He but minimize at ~25% He and then increase, crossing zero at 65–67% (Figure 1). This signifies the transition from “type A”, where K increases at higher E, to “type C”, where K decreases.4,9 This happens because the molecular polarizability is much lower4 for He (0.2 Å3) than for N2 (1.8 Å3) and, thus, the ion–molecule collisions “harden” at higher He fractions; in the limit of hard-shell potential, K decreases2,4 with increasing E. The same transition to type C occurs in N2 at much higher ED ~ 55 kV/cm: extreme fields result in energetic collisions where the dynamics essentially samples only the repulsive part of any ion–molecule potential.25

An expanding application of IMS/MS is the conformational characterization of peptides and separation of their mixtures in proteomics. To exemplify FAIMS in He-rich mixtures for peptides, we have chosen the usual model of bradykinin, Bk (RPPGFSPFR, 1060 Da) with the dominant protonated 2+ ion and syntide 2, St (PLARTLSVAGLPGKK, 1508 Da) that exhibits intense ions with the charge states (z) of 2, 3, and 4. Unlike amino acids, peptides of all z behave as C-type ions9,20,26,27 even in N2. Adding He progressively raises the EC values and narrows the peaks, thus improving the resolving power.20 For typical peptides, going from N2 to 1:1 He/N2 increases EC by ~1.7–2 times and R by ~2 to 3 times: in the present device,20 from ~20 to ~50–60 for Bk2+ conformers and from ~12–40 to ~40–70 for St with z = 2–4. As in conventional IMS, the peaks with any gas become narrower for higher z because the (low-field) diffusion coefficients of ions scale as K/z by the Einstein relationship.2,4,20

Here, as we move above 50% He, the EC values for all features increase further, by ~1.5–1.6 times at 75% He: from ~65–85 V/cm to ~105–135 V/cm for Bk2+ and from ~50–105 to ~75–155 V/cm for St ions (Figure 2). The peaks continue narrowing, as seen for all St charge states. (This is less clear for Bk2+, because of unresolved isomers created by structural transitions as discussed below.) In the result, the resolving power improves by ~1.8–2.5 times over that at 50%: to ~100 for Bk2+ and St2+ and ~180–200 for St3+ and St4+ (Figure 2). To verify the accuracy and reproducibility of these results, we have scanned a narrow window comprising the base peak of St3+ 10 times over 30 min (Figure 3). The mean peak position is 156.52 V/cm with the standard deviation of 0.13 V/cm and maximum deviation of 0.25 V/cm, still ~0.15% in relative terms or ~30% of the peak width. Such a limited EC drift ought to permit accurate measurements with intermittent calibration. The mean peak width is 0.89 V/cm with the relative standard error of 3%, leading to R = 177 ± 11 at 95% confidence. This value comes close to the maxima achieved in conventional IMS, where high-pressure drift-tubes have provided R up to ~170 and ~240 for multiply charged ions,13,14 and far exceeds the metrics for traveling-wave IMS.23,28

Figure 2
Mass-selected FAIMS spectra for bradykinin 2+ (left column) and syntide 2 with z = 2–4 (right column) at 50–75% He. Samples were 20 μM solutions of pure peptides. For well-shaped peaks, we show the widths (V/cm) with the resolving ...
Figure 3
Successive replicates of the peak d for Syntide 3+ in Figure 2 at 75% He, measured in a window of 3.2 V/cm width at the scan speed of 1.06 V/(cm × min). The EC values and peak widths are given for each case.

The peaks for peptides of some z that mirror those for (z + 1) at any He content likely result from the proton transfer after FAIMS filtering.20,29 Such artifacts were noted20 for St2+ and St3+ at ≤50% He and are likely seen here for 3+, where minor features coincide with all four St4+ peaks (a, b, c, and e), Figure 2. However, a strong peak (b) for St3+ at lower EC has no comparable match for St4+ at 60–75% He and, thus, may be not due to charge reduction. The charge transfer appears less intense here than with LCQ MS at the same He fraction,20 possibly because of shorter ion accumulation in the trap or better removal of neutrals in the present MS interface featuring an ion funnel.

For small proteins such as ubiquitin or cytochrome c in any charge state,12,30 unfolding decreases Ec. Two Bk2+ species were resolved by drift-tube IMS,17 and minor features on the low-EC side of the base peak (d) in FAIMS were also ascribed to unfolded conformers.18,20,31 Those features grew in number and relative intensity20 with the He fraction in He/N2 increasing to 50%. As we go to 75% He (Figure 2), the process accelerates with (b) becoming the major peak at ~60% He and further features (grouped under “c”) emerging between the (b) and (d) “book-ends”. Those features have positions and heights sensitive to the solution, source, and/or FAIMS conditions and, hence, likely are intermediates in the isomerization from (d) to (b). Unlike Bk2+ that is a zwitterion,32 most peptides exhibit one major conformer in FAIMS at ≤50% He.20,26 Here, the structures for St ions of any z evolve little between 50% and 75% He. (St4+ has lower EC than the major St3+ conformer probably because it is unfolded by Coulomb repulsion whereas St3+ with one less proton is not.20) The data for ~102 peptides in a protein digest (below) suggest that this behavior is more common than an extensive isomerization seen for Bk2+.

The greater unfolding in He than in N2 has been observed for protein ions in drift-tube IMS.33 The unfolding is induced by field heating (above the gas temperature) by2,4


where M is the gas molecule mass and k is the Boltzmann constant. Thus, ΔT scales33 as Ω−2. All ions have larger cross sections with N2 than with He, and the relative difference increases for smaller ions where the size and other properties of colliding partner are more important. For example,34 for peptides at 250 °C, the difference grows from 16% for neurotensin 3+ (1674 Da) to 24% for kemptide 2+ (773 Da). Hence, the transition from N2 to He should augment the field heating more for peptide ions than for larger proteins. As N2 is more polarizable than He and, thus, forms a deeper potential with any ion,4,25 the differences between the Ω values in N2 and He increase in a colder gas, where attractive interactions contribute to Ω more. For Bk2+, the measured Ω at room temperature in N2 (~336 Å2)25 exceeds that in He (~240 Å2)32,33 by ~40%, thus replacing N2 with He nearly doubles ΔT.

The isomerization in FAIMS appears governed35,36 by the maximum heating at peak E. For Bk2+ in N2 at room temperature,25 the reduced mobility is K0 = 1.22 cm2/(Vs) and the actual mobility is K= (K0 × 298/273) = 1.33 cm2/(Vs). Hence, at the present ED, eq 1 yields ΔT = 92 °C for N2 and 180 °C for He, for a difference of 88 °C. With mobilities by the Blanc’s law, the difference of ΔT is 57 °C between 0% and 75% He and 24 °C between 50% and 75% He. The real differences may be greater because of the non-Blanc effects in gas mixtures.2,4 Based on the drift-tube IMS data,37 heating by >20 °C, leave alone >60 °C, in the >100 °C range may cause major unfolding of peptides during a few milliseconds spent in a capillary. The relevant time scale in the present FAIMS device is longer, allowing further isomerization at equal ΔT. Thus, estimates support the notion that the unfolding of Bk2+ seen in Figure 2 is due to stronger field heating upon He addition.

The FAIMS peak capacity, defined as (separation space)/(mean peak width), for peptide mixtures is proportional to the resolving power for representative peptides and, thus, must increase at higher He content With the commercial cylindrical FAIMS units (Thermo Scientific) operated at ED ~ 20 kV/cm, the R values for most peptides20 are ~5–12 and the peak capacity for tryptic digests of proteomes27 is ~7–9. Thus, the peak capacity for digests is close to the mean R for individual peptides, which makes sense as the peaks densely cover a segment of EC from near zero to a maximum. 11,26,27,3840 Then, the peak capacity of present FAIMS device for digests should range from ~50 at 50% to ~100 at 75% He.

Allowing for single missed cleavages, the in silico tryptic digest of the dominant blood protein, bovine serum albumin (BSA, 66.4 kDa), comprises 144 peptides with 404–3580 Da. At 50% He, all peptide ions are type C with EC ~ 20–100 V/cm for the separation width of ~80 V/cm (Figure 4), consistent with the findings11,3840 using cylindrical FAIMS units at the same gas identity and similar ED. With increasing He content, the spectrum shifts to higher EC while the separation space broadens and, at 75% He, the spectrum takes up the ~27–142 V/cm range with the width of ~115 V/cm (Figure 4). The increases of EC and separation width by ~1.5 times over those at 50% He follow the observations for Bk and St ions.

Figure 4
Total FAIMS spectra for the BSA tryptic digest (1.5 μM by the initial protein content) in He/N2 with 50–75% He. The separation widths are given in V/cm.

Electrospraying tryptic digests typically produces peptide ions with z = 1–5. When the results with cylindrical FAIMS units are reproduced,11,3840 at 50% He, the EC values broadly increase from z = 1 to 2 and further to z = 3–5 (Figure 5). This overall pattern persists to 75% He, but the EC values for different species depend on the He fraction unequally and the peak sequence is not conserved, even within a charge state (Figure 5). Some peptides undergo dramatic EC shifts relative to others, e.g., the ions at m/z = 462 (2+) and m/z = 831 (3+) lie ~1.5% apart and partially overlap at 50% He but are spaced by ~33% (with >10 well-resolved peaks fitting in between) at 75% He. Such shifts could reflect a profound heat-induced isomerization of certain peptides moving them to a different part of the spectrum. Regardless of the cause, these variations allow modifying the separation selectivity by adjusting the He fraction.

Figure 5
FAIMS spectra for selected ions extracted from the data in Figure 4 at 50% He (a) and 75% He (b). We color-code the features by the charge state as labeled, giving the m/z values and (where possible) peak widths (V/cm) underneath. These species were chosen ...

With large shifts rare, the EC values at 50% and 75% He remain strongly correlated (Figure 6). The linear correlation is >0.9 for the full set and z = 1, 2, or 4 alone but only ~0.4 for 3+ ions. This supports the rationalization of the shifts as the manifestation of unfolding, which under present conditions is particularly common for 3+ peptides.

Figure 6
Correlation of FAIMS separation properties at 50% and 75% He for the peptides in Figure 5b (including those absent from Figure 5a), with the same color coding. The line is the first-order regression for the whole data set, and linear correlation coefficients ...

As should be with planar FAIMS gaps,4 the peak widths are independent of EC and tend to decrease for higher z: on average, from ~1.75 V/cm for 1+ to ~1.35 V/cm for 2+ to ~1.15 V/cm for z = 3–5 (Figure 5). The weighted mean over z is 1.4 V/cm, versus ~10 V/cm with cylindrical FAIMS units.20,27 Hence, the total peak capacity is ~50, as was expected from Figure 2. The peaks for all z narrow with increasing He fraction, by ~1/3 at 75% He with the average widths of 1.2 V/cm for 1+, 1.0 V/cm for 2+, and 0.8 V/cm for z = 3–5 (Figure 5). Now, the weighted mean is 1.0 V/cm and the peak capacity is ~110, again close to the estimate from Figure 2. The partial peak capacity for each charge state improves by a similar ~2–2.5 times, e.g., for 1+ from ~15 at 50% He (with the EC range of ~20–45 V/cm) to ~35 at 75% He (with the ~30–72 V/cm range). To eliminate nonpeptide contaminants such as solvent or matrix clusters, proteomic analyses often focus on multiply charged ions. For z = 2–5, the separation width expands from ~45 V/cm (from ~47 to ~92 V/cm) at 50% He to ~74 V/cm (from ~68 to ~142 V/cm) at 75% He, while the weighted mean peak width decreases from ~1.25 V/cm to 0.9 V/cm. Thus, the peak capacity for peptides with z > 1 increases from ~35 at 50% He to ~80 at 75% He. Complex proteomes yield more diverse peptides than BSA and, as with any separation method, the total and partial peak capacities would be even higher.

Ions with EC shifted upon isomerization in FAIMS by more than the peak width are largely removed.4,12,35,41 Hence, isomerization may drastically affect the spectra for specific peptides (as seen for Bk2+ above) but less so for complex mixtures as the peptides that isomerized are suppressed relative to others. This “self-cleaning” mechanism12,35 likely contributes to the paucity of multiple conformers at any He fraction. Some larger multiply charged peptides still exhibit several features, for example, the species at m/z of 632 (4+), 636 (4+), and 801 (5+) with two peaks each (Figure 5). As seen there, those features tend to be separated better at higher He content, and the conformers merged at 50% He are resolved at 75% He. While isomerization in FAIMS may be desired for fundamental studies of ion structure and dynamics, the consequent removal of species impairs sensitivity and, thus, is generally unwelcome from the analytical perspective. One should be able to curb this process via cooling the gas by the greatest ΔT for the set of ions of interest.35


We have demonstrated differential ion mobility spectrometry (FAIMS) in the He/N2 mixtures with up to 75% He, improving the resolution by ~2 to 3 times compared to 1:1 He/N2. This allows full separation of previously unresolved peptide conformers and isomers of small molecules such as leucine and isoleucine. The resolving power for multiply charged peptide ions increases to ~200, producing the peak capacity of ~100 for protein tryptic digests. These parameters compare to those of currently best conventional IMS,1317 but the FAIMS separations are more orthogonal to mass spectrometry.26,42

For deeper fractionation of complex mixtures (e.g., proteome digests) prior to MS and MS/MS analyses, FAIMS has been combined to other separations including conventional MS11,12 or liquid chromatography (LC).27,3840 The increased FAIMS resolution achieved in this work will translate into proportional peak capacity gains for multidimensional separation methods involving FAIMS. In particular, the formal 2-D peak capacity of FAIMS/(drift tube IMS) or LC/FAIMS for proteome digests would increase to ~104 and higher, which compares to or exceeds the metrics of the best 2-D condensed-phase approaches such as MudPIT.43


We thank Ron Moore, Karl Weitz, Carrie Nicora, Gordon Anderson, David Prior, Dr. Satendra Prasad, Dr. Keqi Tang for experimental help, and Dr. Vlad Petyuk and Dr. Matt Monroe for aid in the data analysis. Portions of this research were supported by Battelle and NIH NCRR (RR18522). The work was performed in the PNNL Environmental Molecular Sciences Laboratory, supported by the USDoE Office of Biological and Environmental Research.


1. Aebersold R, Mann M. Nature. 2003;422:198–207. [PubMed]
2. Mason EA, McDaniel EW. Transport Properties of Ions in Gases. Wiley; New York: 1988.
3. Eiceman GA, Karpas Z. Ion Mobility Spectrometry. CRC Press; Boca Raton, FL: 2005.
4. Shvartsburg AA. Differential Ion Mobility Spectrometry. CRC Press; Boca Raton, FL: 2008.
5. Ruotolo BT, Giles K, Campuzano I, Sandercock AM, Bateman RH, Robinson CV. Science. 2005;310:1658–1661. [PubMed]
6. Koeniger SL, Merenbloom SI, Sevugarajan S, Clemmer DE. J Am Chem Soc. 2006;128:11713–11719. [PMC free article] [PubMed]
7. Bernstein SL, Dupuis NF, Lazo ND, Wyttenbach T, Condron MM, Bitan G, Teplow DB, Shea JE, Ruotolo BT, Robinson CV, Bowers MT. Nat Chem. 2009;1:326–331. [PMC free article] [PubMed]
8. Kim HI, Kim H, Pang ES, Ryu EK, Beegle LW, Loo JA, Goddard WA, Kanik I. Anal Chem. 2009;81:8289–8297. [PMC free article] [PubMed]
9. Guevremont R. J Chromatogr, A. 2004;1058:3–19. [PubMed]
10. Robinson EW, Garcia DE, Leib RD, Williams ER. Anal Chem. 2006;78:2190–2198. [PMC free article] [PubMed]
11. Tang K, Li F, Shvartsburg AA, Strittmatter EF, Smith RD. Anal Chem. 2005;77:6381–6388. [PMC free article] [PubMed]
12. Shvartsburg AA, Li F, Tang K, Smith RD. Anal Chem. 2006;78:3304–3315. [PubMed]
13. Dugourd P, Hudgins RR, Clemmer DE, Jarrold MF. Rev Sci Instrum. 1997;68:1122–1129.
14. Srebalus CA, Li J, Marshall WS, Clemmer DE. Anal Chem. 1999;71:3918–3927. [PubMed]
15. Asbury GR, Hill HH. J Microcol Sep. 2000;12:172–178.
16. Tang K, Shvartsburg AA, Lee HN, Prior DC, Buschbach MA, Li F, Tolmachev AV, Anderson GA, Smith RD. Anal Chem. 2005;77:3330–3339. [PMC free article] [PubMed]
17. Kemper PR, Dupuis NR, Bowers MT. Int J Mass Spectrom. 2009;287:46–57.
18. Shvartsburg AA, Li R, Tang K, Smith RD. Anal Chem. 2006;78:3706–3714. [PMC free article] [PubMed]
19. Mabrouki R, Kelly RT, Prior DC, Shvartsburg AA, Tang K, Smith RD. J Am Soc Mass Spectrom. 2009;20:1768–1774. [PMC free article] [PubMed]
20. Shvartsburg AA, Tang K, Smith RD. Anal Chem. 2010;82:32–35. [PMC free article] [PubMed]
21. Ruotolo BT, McLean JA, Gillig KJ, Russell DH. J Mass Spectrom. 2004;39:361–367. [PubMed]
22. Page J, Tang K, Smith RD. Int J Mass Spectrom. 2007;265:244–250.
23. Knapman TW, Berryman JT, Campuzano I, Harris SA, Ashcroft AE. Int J Mass Spectrom. doi: 10.1016/j.ijms.2009.09.011. [Cross Ref]
24. Barnett DA, Ells B, Guevremont R, Purves RW. J Am Soc Mass Spectrom. 1999;10:1279–1284.
25. Shvartsburg AA, Tang K, Smith RD, Holden M, Rush M, Thompson A, Toutoungi D. Anal Chem. 2009;81:8048–8053. [PMC free article] [PubMed]
26. Guevremont R, Barnett DA, Purves RW, Vandermey J. Anal Chem. 2000;72:4577–4584. [PubMed]
27. Canterbury JD, Yi X, Hoopmann MR, MacCoss MJ. Anal Chem. 2008;80:6888–6897. [PMC free article] [PubMed]
28. Shvartsburg AA, Smith RD. Anal Chem. 2008;80:9689–9699. [PMC free article] [PubMed]
29. Purves RW, Barnett DA, Ells B, Guevremont R. J Am Soc Mass Spectrom. 2001;12:894–901. [PubMed]
30. Purves RW, Barnett DA, Ells B, Guevremont R. J Am Soc Mass Spectrom. 2000;11:738–745. [PubMed]
31. Purves RW, Barnett DA, Ells B, Guevremont R. Rapid Commun Mass Spectrom. 2001;15:1453–1456. [PubMed]
32. Rodriquez CF, Orlova G, Guo Y, Li X, Siu CK, Hopkinson AC, Siu KWM. J Phys Chem B. 2006;110:7528–7537. [PubMed]
33. Baker ES, Clowers BH, Li F, Tang K, Tolmachev AV, Prior DC, Belov ME, Smith RD. J Am Soc Mass Spectrom. 2007;18:1176–1187. [PubMed]
34. Hill HH, Hill CH, Asbury GR, Wu C, Mate LM, Ichiye T. Int J Mass Spectrom. 2002;219:23–37.
35. Shvartsburg AA, Li F, Tang K, Smith RD. Anal Chem. 2007;79:1523–1528. [PubMed]
36. Robinson EW, Shvartsburg AA, Tang K, Smith RD. Anal Chem. 2008;80:7508–7515. [PMC free article] [PubMed]
37. Li J, Taraszka JA, Counterman AE, Clemmer DE. Int J Mass Spectrom. 1997;185/186/187:37–47.
38. Venne K, Bonneil E, Eng K, Thibault P. Anal Chem. 2005;77:2176–2186. [PubMed]
39. Xia YQ, Wu ST, Jemal M. Anal Chem. 2008;80:7137–7143. [PubMed]
40. Saba J, Bonneil E, Pomies C, Eng K, Thibault P. J Proteome Res. 2009;8:3355–3366. [PubMed]
41. Purves RW, Ells B, Barnett DA, Guevremont R. Can J Chem. 2005;83:1961–1968.
42. Shvartsburg AA, Mashkevich SV, Smith RD. J Phys Chem A. 2006;110:2663–2673. [PubMed]
43. Washburn MP, Wolters D, Yates JR. Nat Biotechnol. 2001;19:242–247. [PubMed]