Abstract
Simulations show that significant ion losses occur within the commercial electrospray ionization-field asymmetric waveform ion mobility spectrometer (ESI-FAIMS) interface owing to an angular desolvation gas flow and because of the impact of the FAIMS carrier gas onto the inner rf (radio frequency) electrode. The angular desolvation gas flow diverts ions away from the entrance plate orifice while the carrier gas annihilates ions onto the inner rf electrode. A novel ESI-FAIMS interface is described that optimizes FAIMS gas flows resulting in large improvements in transmission. Simulations with the bromochloroacetate anion showed an improvement of ~9-fold to give ~70% overall transmission). Comparable transmission improvements were attained experimentally for six peptides (2+) in the range of m/z 404.2 to 653.4 at a chromatographic flow rate of 300 nL/min. Selected ion chromatograms (SIC) from nano-LC-FAIMS-MS analyses showed 71% (HLVDEPQNLIK, m/z 653.4, 2+) to 95% (LVNELTEFAK, m/z 582.3, 2+) of ion signal compared with ion signal in the SIC from LC-MS analysis. IGSEVYHNLK (580.3, 2+) showed 24% more ion signal compared with LC-MS and is explained by enhanced desolvation in FAIMS. A 3–10 times lower limits of quantitation (LOQ) (<15% RSD) was achieved for chemical noise limited peaks with FAIMS. Peaks limited by ion statistics showed subtle improvement in RSD and yielded comparable LOQ to that attained with nano-LC-MS (without FAIMS). These improvements were obtained using a reduced FAIMS separation gap (from 2.5 to 1.5 mm) that results in a shorter residence time (13.2 ms ± 3.9 ms) and enables the use of a helium free transport gas (100% nitrogen).
Similar content being viewed by others
References
Houel, S., Abernathy, R., Renganathan, K., Meyer-Arendt, K., Ahn, N.G., Old, W.M.: Quantifying the impact of chimera MS/MS spectra on peptide identification in large-scale proteomics studies. J. Proteome Res. 9(8), 4152–4160 (2010)
Michalski, A., Cox, J., Mann, M.: More than 100,000 detectable peptide species elute in single shotgun proteomics runs but the majority is inaccessible to data-dependent LC-MS/MS. J. Proteome Res. 10(4), 1785–1793 (2011)
Bateman, N.W., Goulding, S.P., Shulman, N.J., Gadok, A.K., Szumlinski, K.K., MacCoss, M.J., Wu, C.C.: Maximizing peptide identification events in proteomic workflows using data-dependent acquisition (DDA). Mol. Cell Proteom. 13(1), 329–338 (2014)
Stahl, D.C., Swiderek, K.M., Davis, M.T., Lee, T.D.: Data-controlled automation of liquid chromatography/tandem mass spectrometry analysis of peptide mixtures. J. Am. Soc. Mass Spectrom. 7(6), 532–540 (1996)
Yates III, J.R., Eng, J.K., McCormack, A.L., Schieltz, D.: Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. Anal. Chem. 67(8), 1426–1436 (1995)
Johnson, D., Boyes, B., Fields, T., Kopkin, R., Orlando, R.: Optimization of data-dependent acquisition parameters for coupling high-speed separations with LC-MS/MS for protein identifications. J. Biomol. Technol. 24(2), 62–72 (2013)
Hodge, K., Have, S.T., Hutton, L., Lamond, A.I.: Cleaning up the masses: exclusion lists to reduce contamination with HPLC-MS/MS. J. Proteom. 88, 92–103 (2013)
Zhang, Y., Wen, Z., Washburn, M.P., Florens, L.: Effect of dynamic exclusion duration on spectral count based quantitative proteomics. Anal. Chem. 81(15), 6317–6326 (2009)
Geromanos, S.J., Vissers, J.P., Silva, J.C., Dorschel, C.A., Li, G.Z., Gorenstein, M.V., Bateman, R.H., Langridge, J.I.: The detection, correlation, and comparison of peptide precursor and product ions from data independent LC-MS with data dependant LC-MS/MS. Proteomics 9(6), 1683–1695 (2009)
Baker, E.S., Livesay, E.A., Orton, D.J., Moore, R.J., Danielson, W.F., Prior, D.C., Ibrahim, Y.M., LaMarche, B.L., Mayampurath, A.M., Schepmoes, A.A., Hopkins, D.F., Tang, K., Smith, R.D., Belov, M.E.: An LC-IMS-MS platform providing increased dynamic range for high-throughput proteomic studies. J. Proteome Res. 9(2), 997–1006 (2009)
Barnett, D.A., Ells, B., Guevremont, R., Purves, R.W.: Application of ESI-FAIMS-MS to the analysis of tryptic peptides. J. Am. Soc. Mass Spectrom. 13(11), 1282–1291 (2002)
Purves, R.W., Barnett, D.A., Ells, B., Guevremont, R.: Elongated conformers of charge states +11 to +15 of bovine ubiquitin studied using ESI-FAIMS-MS. J. Am. Soc. Mass Spectrom. 12(8), 894–901 (2001)
Saba, J., Bonneil, E., Pomies, C., Eng, K., Thibault, P.: Enhanced sensitivity in proteomics experiments using FAIMS coupled with a hybrid linear ion trap/Orbitrap mass spectrometer. J. Proteome Res. 8(7), 3355–3366 (2009)
Swearingen, K.E., Hoopmann, M.R., Johnson, R.S., Saleem, R.A., Aitchison, J.D., Moritz, R.L.: Nanospray FAIMS fractionation provides significant increases in proteome coverage of unfractionated complex protein digests. Mol. Cell Proteom. 11(4), M111.014985 (2012)
Venne, K., Bonneil, E., Eng, K., Thibault, P.: Improvement in peptide detection for proteomics analyses using NanoLC-MS and high-field asymmetry waveform ion mobility mass spectrometry. Anal. Chem. 77(7), 2176–2186 (2005)
Shvartsburg, A.A., Tang, K., Smith, R.D.: Optimization of the design and operation of FAIMS analyzers. J. Am. Soc. Mass Spectrom. 16(1), 2–12 (2005)
Canterbury, J.D., Yi, X., Hoopmann, M.R., MacCoss, M.J.: Assessing the dynamic range and peak capacity of nanoflow LC-FAIMS-MS on an ion trap mass spectrometer for proteomics. Anal. Chem. 80(18), 6888–6897 (2008)
Wu, S.T., Xia, Y.Q., Jemal, M.: High-field asymmetric waveform ion mobility spectrometry coupled with liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-FAIMS-MS/MS) multi-component bioanalytical method development, performance evaluation and demonstration of the constancy of the compensation voltage with change of mobile phase composition or flow rate. Rapid Commun. Mass Spectrom. 21(22), 3667–3676 (2007)
Kapron, J., Wu, J., Mauriala, T., Clark, P., Purves, R.W., Bateman, K.P.: Simultaneous analysis of prostanoids using liquid chromatography/high-field asymmetric waveform ion mobility spectrometry/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 20(10), 1504–1510 (2006)
Yost, R.A., Beekman, C.R., Boock, J.J., Garrett, T.J., Ray, J.A., Kushnir, M.M., Rockwood, A.L.: Proceedings of the 61st ASMS Conference: Minneapolis, MN (2013).
Ells, B., Barnett, D.A., Froese, K., Purves, R.W., Hrudey, S., Guevremont, R.: Detection of chlorinated and brominated byproducts of drinking water disinfection using electrospray ionization-high-field asymmetric waveform ion mobility spectrometry-mass spectrometry. Anal. Chem. 71(20), 4747–4752 (1999)
Hatsis, P., Kapron, J.T.: A review on the application of high-field asymmetric waveform ion mobility spectrometry (FAIMS) in drug discovery. Rapid Commun. Mass Spectrom. 22(5), 735–738 (2008)
Xia, Y.Q., Wu, S.T., Jemal, M.: LC-FAIMS-MS/MS for quantification of a peptide in plasma and evaluation of FAIMS global selectivity from plasma components. Anal. Chem. 80(18), 7137–7143 (2008)
Shvartsburg, A.A., Tang, K., Smith, R.D.: Modeling the resolution and sensitivity of FAIMS analyses. J. Am. Soc. Mass Spectrom. 15(10), 1487–1498 (2004)
Barnett, D.A., Ouellette, R.J.: Elimination of the helium requirement in high-field asymmetric waveform ion mobility spectrometry (FAIMS): beneficial effects of decreasing the analyzer gap width on peptide analysis. Rapid Commun. Mass Spectrom. 25(14), 1959–1971 (2011)
Prasad, S., Belford, M.W., Dunyach, J-J.: Control of gas flow in high field asymmetric waveform ion mobility spectrometry. US Patent number 8,664,593,B2 (2014).
Krylov, E.V., Nazarov, E.G., Miller, R.A.: Differential mobility spectrometer: Model of operation. Int. J. of Mass Spectrom. 266(1/3), 76–85 (2007)
Tang, K., Li, F., Shvartsburg, A.A., Strittmatter, E.F., Smith, R.D.: Two-dimensional gas-phase separations coupled to mass spectrometry for analysis of complex mixtures. Anal. Chem. 77(19), 6381–6388 (2005)
Purves, R.W., Ozog, A.R., Ambrose, S.J., Prasad, S., Belford, M., Dunyach, J.J.: Using gas modifiers to significantly improve sensitivity and selectivity in a cylindrical FAIMS device. J. Am. Soc. Mass Spectrom. 25(7), 1274–1284 (2014)
Barnett, D.A., Belford, M., Dunyach, J.J., Purves, R.W.: Characterization of a temperature-controlled FAIMS system. J. Am. Soc. Mass Spectrom. 18(9), 1653–1663 (2007)
Swearingen, K.E., Hoopmann, M.R., Moritz, R.L.: Proceedings of the 61st ASMS Conference: Proceedings of the 61st ASMS Conference on Mass Spectrometry and Allied Topics, Minneapolis, MN, June 9–13, (2013).
Guevremont, R., Purves, R.W.: Atmospheric pressure ion focusing in a high-field asymmetric waveform ion mobility spectrometer. Rev. Sci. Instrum. 70(2), 1370–1383 (1999)
Tang, K., Shvartsburg, A.A., Smith, R.D.: Interface and process for enhanced transmission of non-circular ion beams between stages at unequal pressure. US Patent number 7,339,166 B2 (2008).
Mabrouki, R., Kelly, R.T., Prior, D.C., Shvartsburg, A.A., Tang, K., Smith, R.D.: Improving FAIMS sensitivity using a planar geometry with slit interfaces. J. Am. Soc. Mass Spectrom. 20(9), 1768–1774 (2009)
Belford, M.W., Kovtoun, V.V.: Flat plate FAIMS with lateral ion focusing. US Patent number 7,851,745 B2 (2010).
Shvartsburg, A.A., Tang, K., Ibrahim, Y.M., Smith, R.D.: Hooked differential mobility spectrometry apparatus and method therefore. US Patent number 7,491,930 B2 (2009).
Shvartsburg, A.A., Tang, K., Smith, R.D.: FAIMS operation for realistic gas flow profile and asymmetric waveforms including electronic noise and ripple. J. Am. Soc. Mass Spectrom. 16(9), 1447–1455 (2005)
Prasad, S., Tang, K., Manura, D., Papanastasiou, D., Smith, R.D.: Simulation of Ion Motion in FAIMS through combined use of SIMION and modified SDS. Anal. Chem. 81(21), 8749–8757 (2009)
Cumeras, R., Gràcia, I., Figueras, E., Fonseca, L., Santander, J., Salleras, M., Calaza, C., Sabaté, N., Cané, C.: Modeling a P-FAIMS with multiphysics FEM. J. Math Chem. 50(2), 359–373 (2012)
Guevremont, R., Purves, R.: Comparison of experimental and calculated peak shapes for three cylindrical geometry FAIMS prototypes of differing electrode diameters. J. Am. Soc. Mass Spectrom. 16(3), 349–362 (2005)
Wissdorf, W., Pohler, L., Klee, S., Muller, D., Benter, T.: Simulation of ion motion at atmospheric pressure: particle tracing versus electrokinetic flow. J. Am. Soc. Mass Spectrom. 23(2), 397–406 (2012)
Wissdorf, W., Lorenz, M., Pohler, T., Honen, H., Benter, T.: Atmospheric pressure ion source development: experimental validation of simulated ion trajectories within complex flow and electrical fields. J. Am. Soc. Mass Spectrom. 24(10), 1456–1466 (2013)
Garimella, S., Zhou, X., Ouyang, Z.: Simulation of rarefied gas flows in atmospheric pressure interfaces for mass spectrometry systems. J. Am. Soc. Mass Spectrom. 24(12), 1890–1899 (2013)
Belford, M., Prasad, S., Dunyach, J.-J.: Proceedings of the 60th ASMS Conference on Mass Spectrometry and Allied Topics, Vancouver, CA, May 20–24 (2012).
Belford, M., Prasad, S., Dunyach, J.-J.: Proceedings of the 61st ASMS Conference on Mass Spectrometry and Allied Topics, Minneapolis, MN, June 9–13, (2013).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Online Resource 1
(DOCX 23 kb)
Online Resource 2
(DOCX 38 kb)
Online Resource 3
(DOCX 263 kb)
Rights and permissions
About this article
Cite this article
Prasad, S., Belford, M.W., Dunyach, JJ. et al. On an Aerodynamic Mechanism to Enhance Ion Transmission and Sensitivity of FAIMS for Nano-Electrospray Ionization-Mass Spectrometry. J. Am. Soc. Mass Spectrom. 25, 2143–2153 (2014). https://doi.org/10.1007/s13361-014-0995-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13361-014-0995-8