Characterization of Electrospray Ionization (ESI) Parameters on In-ESI Hydrogen/Deuterium Exchange of Carbohydrate-Metal Ion Adducts

  • O. Tara Liyanage
  • Matthew R. Brantley
  • Emvia I. Calixte
  • Touradj Solouki
  • Kevin L. Shuford
  • Elyssia S. GallagherEmail author
Research Article


The conformations of glycans are crucial for their biological functions. In-electrospray ionization (ESI) hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is a promising technique for studying carbohydrate conformations since rapidly exchanging functional groups, e.g., hydroxyls, can be labeled on the timeframe of ESI. However, regular application of in-ESI HDX to characterize carbohydrates requires further analysis of the in-ESI HDX methodology. For instance, in this method, HDX occurs concurrently to the analyte transitioning from solution to gas-phase ions. Therefore, there is a possibility of sampling both gas-phase and solution-phase conformations of the analyte. Herein, we differentiate in-ESI HDX of metal-adducted carbohydrates from gas-phase HDX and illustrate that this method analyzes solvated species. We also systematically examine the effects of ESI parameters, including spray solvent composition, auxiliary gas flow rate, sheath gas flow rate, sample infusion rate, sample concentration, and spray voltage, and discuss their effects on in-ESI HDX. Further, we model the structural changes of a trisaccharide, melezitose, and its intramolecular and intermolecular hydrogen bonding in solvents with different compositions of methanol and water. These molecular dynamic simulations support our experimental results and illustrate how an individual ESI parameter can alter the conformations we sample by in-ESI HDX. In total, this work illustrates how the fundamental processes of ESI alter the magnitude of HDX for carbohydrates and suggest parameters that should be considered and/or optimized prior to performing experiments with this in-ESI HDX technique.

Graphical Abstract


Electrospray ionization Hydrogen/deuterium exchange Mass spectrometry Carbohydrate Conformation 



O.T.L. and E.S.G. were supported by The Welch Foundation under award number AA-1899. M.R.B. and T.S. were supported by NSF IDBR award number 1455668. E.I.C. and K.L.S. were supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy under Award Number DE-SC0019327. We thank the Baylor Mass Spectrometry Center (MSC) for providing instruments and resources used to collect the data presented here. We thank Baylor University’s High Performance and Research Computing Services (HPRCS) for technical support and access to the cluster (Kodiak). We thank H. Jamie Kim and Ian G. M. Anthony for assistance with solution-phase HDX experiments and data presentation software, respectively.

Supplementary material

13361_2018_2080_MOESM1_ESM.docx (11.6 mb)
ESM 1 (DOCX 11.6 mb)


  1. 1.
    Bucior, I., Burger, M.M.: Carbohydrate–carbohydrate interactions in cell recognition. Curr. Opin. Struct. Biol. 14, 631–637 (2004)CrossRefGoogle Scholar
  2. 2.
    Le Pendu, J., Nyström, K., Ruvoën-Clouet, N.: Host–pathogen co-evolution and glycan interactions. Curr. Opin. Virol. 7, 88–94 (2014)CrossRefGoogle Scholar
  3. 3.
    Freeze, H.H., Kinoshita, T., Varki, A.: Glycans in acquired human diseases. In: Varki, a., Cummings, R.D., Esko, J.D., (Eds) Essentials of Glycobiology (3rd Ed.). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, Chapter 46. (2017)Google Scholar
  4. 4.
    Dube, D.H., Bertozzi, C.R.: Glycans in cancer and inflammation—potential for therapeutics and diagnostics. Nat. Rev. Drug Discov. 4, 477–488 (2005)CrossRefGoogle Scholar
  5. 5.
    Qin, R., Zhao, J., Qin, W., Zhang, Z., Zhao, R., Han, J., Yang, Y., Li, L., Wang, X., Ren, S., Sun, Y., Gu, J.: Discovery of non-invasive glycan biomarkers for detection and surveillance of gastric cancer. J. Cancer. 8, 1908–1916 (2017)CrossRefGoogle Scholar
  6. 6.
    Adamczyk, B., Tharmalingam, T., Rudd, P.M.: Glycans as cancer biomarkers. Biochim. Biophys. Acta. 1820, 1347–1353 (2012)CrossRefGoogle Scholar
  7. 7.
    Ocho, M., Togayachi, A., Iio, E., Kaji, H., Kuno, A., Sogabe, M., Korenaga, M., Gotoh, M., Tanaka, Y., Ikehara, Y., Mizokami, M., Narimatsu, H.: Application of a Glycoproteomics-based biomarker development method: alteration in glycan structure on colony stimulating factor 1 receptor as a possible glycobiomarker candidate for evaluation of liver cirrhosis. J. Proteome Res. 13, 1428–1437 (2014)CrossRefGoogle Scholar
  8. 8.
    Akinkuolie, A.O., Buring, J.E., Ridker, P.M., Mora, S.: A novel protein glycan biomarker and future cardiovascular disease events. J. Am. Heart Assoc. 3, e001221 (2014)CrossRefGoogle Scholar
  9. 9.
    An, H.J., Kronewitter, S.R., de Leoz, M.L.A., Lebrilla, C.B.: Glycomics and disease markers. Curr. Opin. Chem. Biol. 13, 601–607 (2009)CrossRefGoogle Scholar
  10. 10.
    Bertozzi, C.R., Rabuka, D.: Structural basis of glycan diversity. In: Varki, A., Cummings, R.D., Esko, J.D., Freeze, H.H., Stanley, P., Bertozzi, C.R., Hart, G.W., Etzler, M.E. (eds.) Essentials of Glycobiology (2nd Ed.). Cold Spring Harbor Laboratory Press, p. 2. Chapter, Cold Spring Harbor (2009)Google Scholar
  11. 11.
    Kizuka, Y., Kitazume, S., Fujinawa, R., Saito, T., Iwata, N., Saido, T.C., Nakano, M., Yamaguchi, Y., Hashimoto, Y., Staufenbiel, M., Hatsuta, H., Murayama, S., Manya, H., Endo, T., Taniguchi, N.: An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer disease. EMBO Mol Med. 7, 175 (2015)CrossRefGoogle Scholar
  12. 12.
    Nagae, M., Kanagawa, M., Morita-Matsumoto, K., Hanashima, S., Kizuka, Y., Taniguchi, N., Yamaguchi, Y.: Atomic visualization of a flipped-back conformation of bisected glycans bound to specific lectins. Sci. Rep. 6, 22973 (2016)CrossRefGoogle Scholar
  13. 13.
    Nagae, M., Yamaguchi, Y.: Function and 3D structure of the N-glycans on glycoproteins. Int. J. Mol. Sci. 13, 8398–8429 (2012)CrossRefGoogle Scholar
  14. 14.
    Wormald, M.R., Petrescu, A.J., Pao, Y.-L., Glithero, A., Elliott, T., Dwek, R.A.: Conformational studies of oligosaccharides and glycopeptides: complementarity of NMR, X-ray crystallography, and molecular modelling. Chem. Rev. 102, 371–386 (2002)CrossRefGoogle Scholar
  15. 15.
    Thomas, W.A.: Nuclear magnetic resonance spectroscopy in conformational analysis. Annu. Rev. NMR Spectrosc., academic press, Cambridge. MA. 1, 43–89 (1968)Google Scholar
  16. 16.
    Bohrer, B.C., Merenbloom, S.I., Koeniger, S.L., Hilderbrand, A.E., Clemmer, D.E.: Biomolecule analysis by ion mobility spectrometry. Annu. Rev. Anal. Chem. 1, 293–327 (2008)CrossRefGoogle Scholar
  17. 17.
    Verbeck, G., Ruotolo, B., Sawyer, H., Gillig, K., Russell, D.: A fundamental introduction to ion mobility mass spectrometry applied to the analysis of biomolecules. J. Biomol. Tech. 13, 56–61 (2002)Google Scholar
  18. 18.
    Englander, S.W.: Hydrogen exchange and mass spectrometry: a historical perspective. J. Am. Soc. Mass Spectrom. 17, 1481–1489 (2006)CrossRefGoogle Scholar
  19. 19.
    Engen, J.R.: Analysis of protein conformation and dynamics by hydrogen/deuterium exchange MS. Anal. Chem. 81, 7870–7875 (2009)CrossRefGoogle Scholar
  20. 20.
    Gallagher, E.S., Hudgens, J.W.: Mapping protein–ligand interactions with proteolytic fragmentation, hydrogen/deuterium exchange-mass spectrometry in:Kelman, Z (eds.)methods in enzymology pg 357-404, academic press, Cambridge (MA). In: 566 (2016)Google Scholar
  21. 21.
    Huang, Y., Dodds, E.D.: Ion mobility studies of carbohydrates as group I adducts: isomer specific collisional cross section dependence on metal ion radius. Anal. Chem. 85, 9728–9735 (2013)CrossRefGoogle Scholar
  22. 22.
    Huang, Y., Dodds, E.D.: Discrimination of isomeric carbohydrates as the electron transfer products of group II cation adducts by ion mobility spectrometry and tandem mass spectrometry. Anal. Chem. 87, 5664–5668 (2015)CrossRefGoogle Scholar
  23. 23.
    Clowers, B.H., Dwivedi, P., Steiner, W.E., Hill, H.H., Bendiak, B.: Separation of sodiated isobaric disaccharides and trisaccharides using electrospray ionization-atmospheric pressure ion mobility-time of flight mass spectrometry. J. Am. Soc. Mass Spectrom. 16, 660–669 (2005)CrossRefGoogle Scholar
  24. 24.
    Fenn, L.S., McLean, J.A.: Structural resolution of carbohydrate positional and structural isomers based on gas-phase ion mobility-mass spectrometry. Phys. Chem. Chem. Phys. 13, 2196–2205 (2011)CrossRefGoogle Scholar
  25. 25.
    Li, H., Giles, K., Bendiak, B., Kaplan, K., Siems, W.F., Hill, H.H.: Resolving structural isomers of monosaccharide methyl glycosides using drift tube and traveling wave ion mobility mass spectrometry. Anal. Chem. 84, 3231–3239 (2012)CrossRefGoogle Scholar
  26. 26.
    Pettit, M.E., Brantley, M.R., Donnarumma, F., Murray, K.K., Solouki, T.: Broadband ion mobility deconvolution for rapid analysis of complex mixtures. Analyst. 143, 2574–2586 (2018)CrossRefGoogle Scholar
  27. 27.
    Kirschner, K.N., Woods, R.J.: Solvent interactions determine carbohydrate conformation. Proc. Natl. Acad. Sci. 98, 10541–10545 (2001)CrossRefGoogle Scholar
  28. 28.
    Kaltashov, I.A., Bobst, C.E., Abzalimov, R.R., Berkowitz, S.A., Houde, D.: Conformation and dynamics of biopharmaceuticals: transition of mass spectrometry-based tools from academe to industry. J. Am. Soc. Mass Spectrom. 21, 323–337 (2010)CrossRefGoogle Scholar
  29. 29.
    Kleckner, I.R., Foster, M.P.: An introduction to NMR-based approaches for measuring protein dynamics. Biochim. Biophys. Acta. 1814, 942–968 (2011)CrossRefGoogle Scholar
  30. 30.
    Lindner, R., Heintz, U., Winkler, A.: Applications of hydrogen deuterium exchange (HDX) for the characterization of conformational dynamics in light-activated photoreceptors. Front. Mol. Biosci. 2, 33 (2015)CrossRefGoogle Scholar
  31. 31.
    Guttman, M., Scian, M., Lee, K.K.: Tracking hydrogen/deuterium exchange at glycan sites in glycoproteins by mass spectrometry. Anal. Chem. 83, 7492–7499 (2011)CrossRefGoogle Scholar
  32. 32.
    Mao, D., Douglas, D.J.: H/D exchange of gas phase bradykinin ions in a linear quadrupole ion trap. J. Am. Soc. Mass Spectrom. 14, 85–94 (2003)CrossRefGoogle Scholar
  33. 33.
    Green-Church, K.B., Limbach, P.A., Freitas, M.A., Marshall, A.G.: Gas-phase hydrogen/deuterium exchange of positively charged mononucleotides by use of Fourier-transform ion cyclotron resonance mass spectrometry. J. Am. Soc. Mass Spectrom. 12, 268–277 (2001)CrossRefGoogle Scholar
  34. 34.
    Miladi, M., Olaitan, A.D., Zekavat, B., Solouki, T.: Competing noncovalent host-guest interactions and H/D exchange: reactions of benzyloxycarbonyl-proline glycine dipeptide variants with ND3. J. Am. Soc. Mass Spectrom. 26, 1938–1949 (2015)CrossRefGoogle Scholar
  35. 35.
    Zekavat, B., Miladi, M., Al-Fdeilat, A.H., Somogyi, A., Solouki, T.: Evidence for sequence scrambling and divergent H/D exchange reactions of doubly-charged isobaric b-type fragment ions. J. Am. Soc. Mass Spectrom. 25, 226–236 (2014)CrossRefGoogle Scholar
  36. 36.
    Nagy, K., Redeuil, K., Rezzi, S.: Online hydrogen/deuterium exchange performed in the ion mobility cell of a hybrid mass spectrometer. Anal. Chem. 81, 9365–9371 (2009)CrossRefGoogle Scholar
  37. 37.
    Mistarz, U.H., Brown, J.M., Haselmann, K.F., Rand, K.D.: Probing the binding interfaces of protein complexes using gas-phase H/D exchange mass spectrometry. Structure. 24, 310–318 (2016)CrossRefGoogle Scholar
  38. 38.
    Uppal, S.S., Beasley, S.E., Scian, M., Guttman, M.: Gas-phase hydrogen/deuterium exchange for distinguishing isomeric carbohydrate ions. Anal. Chem. 89, 4737–4742 (2017)CrossRefGoogle Scholar
  39. 39.
    Takáts, Z., Schlosser, G., Vékey, K.: Hydrogen/deuterium exchange of electrosprayed ions in the atmospheric interface of a commercial triple–quadrupole mass spectrometer. Int. J. Mass Spectrom. 228, 729–741 (2003)CrossRefGoogle Scholar
  40. 40.
    Wolff, J.C., Laures Alice, M.F.: ‘On-the-fly’ hydrogen/deuterium exchange liquid chromatography/mass spectrometry using a dual-sprayer atmospheric pressure ionisation source. Rapid Commun. Mass Spectrom. 20, 3769–3779 (2006)CrossRefGoogle Scholar
  41. 41.
    Kostyukevich, Y., Kononikhin, A., Popov, I., Nikolaev, E.: Simple atmospheric hydrogen/deuterium exchange method for enumeration of labile hydrogens by electrospray ionization mass spectrometry. Anal. Chem. 85, 5330–5334 (2013)CrossRefGoogle Scholar
  42. 42.
    Tittebrandt, S., Edelson-Averbukh, M., Spengler, B., Lehmann, W.D.: ESI hydrogen/deuterium exchange can count chemical forms of heteroatom-bound hydrogen. Angew. Chem. Int. Ed. 52, 8973–8975 (2013)CrossRefGoogle Scholar
  43. 43.
    Kostyukevich, Y., Kononikhin, A., Popov, I., Nikolaev, E.: In-ESI source hydrogen/deuterium exchange of carbohydrate ions. Anal. Chem. 86, 2595–2600 (2014)CrossRefGoogle Scholar
  44. 44.
    Kostyukevich, Y., Kononikhin, A., Popov, I., Nikolaev, E.: Conformations of cationized linear oligosaccharides revealed by FTMS combined with in-ESI H/D exchange. J. Mass Spectrom. 50, 1150–1156 (2015)CrossRefGoogle Scholar
  45. 45.
    Zherebker, A., Kostyukevich, Y., Kononikhin, A., Roznyatovsky, V.A., Popov, I., Grishin, Y.K., Perminova, I.V., Nikolaev, E.: High desolvation temperature facilitates in ESI-source H/D exchange at non-labile sites of hydroxybenzoic acids and aromatic amino acids. Analyst. 141, 2426–2434 (2016)CrossRefGoogle Scholar
  46. 46.
    Acter, T., Lee, S., Cho, E., Jung, M.-J., Kim, S.: Design and validation of in-source atmospheric pressure photoionization hydrogen/deuterium exchange mass spectrometry with continuous feeding of D2O. J. Am. Soc. Mass Spectrom. 29, 85–94 (2018)CrossRefGoogle Scholar
  47. 47.
    Ahmed, A., Choi, C., Kim, S.: Mechanistic study on lowering the sensitivity of positive atmospheric pressure photoionization mass spectrometric analyses: size-dependent reactivity of solvent clusters. Rapid Commun. Mass Spectrom. 29, 2095–2101 (2015)CrossRefGoogle Scholar
  48. 48.
    Konermann, L., Ahadi, E., Rodriguez, A.D., Vahidi, S.: Unraveling the mechanism of electrospray ionization. Anal. Chem. 85, 2–9 (2013)CrossRefGoogle Scholar
  49. 49.
    Iribarne, J.V., Thomson, B.A.: On the evaporation of small ions from charged droplets. J. Chem. Phys. 64, 2287–2294 (1976)CrossRefGoogle Scholar
  50. 50.
    Znamenskiy, V., Marginean, I., Vertes, A.: Solvated ion evaporation from charged water Nanodroplets. J. Phys. Chem. A. 107, 7406–7412 (2003)CrossRefGoogle Scholar
  51. 51.
    Ahadi, E., Konermann, L.: Ejection of solvated ions from Electrosprayed methanol/water Nanodroplets studied by molecular dynamics simulations. J. Am. Chem. Soc. 133, 9354–9363 (2011)CrossRefGoogle Scholar
  52. 52.
    Kim, H.J., Liyanage, O.T., Mulenos, M.R., Gallagher, E.S.: Mass spectral detection of forward- and reverse-hydrogen/deuterium exchange resulting from residual solvent vapors in electrospray sources. J. Am. Soc. Mass Spectrom. 29, 2030–2040 (2018)CrossRefGoogle Scholar
  53. 53.
    MATLAB: And statistics toolbox release 2016a, the MathWorks, Inc., Natick, Massachusetts. United States.Google Scholar
  54. 54.
    Hess, B., Kutzner, C., van der Spoel, D., Lindahl, E.: GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435–447 (2008)CrossRefGoogle Scholar
  55. 55.
    Guvench, O., Mallajosyula, S.S., Raman, E.P., Hatcher, E., Vanommeslaeghe, K., Foster, T.J., Jamison, F.W., MacKerell, A.D.: CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate–protein modeling. J. Chem. Theory Comput. 7, 3162–3180 (2011)CrossRefGoogle Scholar
  56. 56.
    Sterling, T., Irwin, J.J.: ZINC 15—ligand discovery for everyone. J. Chem. Inf. Model. 55, 2324–2337 (2015)CrossRefGoogle Scholar
  57. 57.
    Berendsen, H.J.C., Grigera, J.R., Straatsma, T.P.: The missing term in effective pair potentials. J. Phys. Chem. 91, 6269–6271 (1987)CrossRefGoogle Scholar
  58. 58.
    Bussi, G., Donadio, D., Parrinello, M.: Canonical sampling through velocity rescaling. J. Chem. Phys. 126, 014101 (2007)CrossRefGoogle Scholar
  59. 59.
    Parrinello, M., Rahman, A.: Polymorphic transitions in single crystals: a new molecular dynamics method. J. Appl. Phys. 52, 7182–7190 (1981)CrossRefGoogle Scholar
  60. 60.
    Nosé, S., Klein, M.L.: Constant pressure molecular dynamics for molecular systems. Mol. Phys. 50, 1055–1076 (1983)CrossRefGoogle Scholar
  61. 61.
    Verlet, L.: Computer "experiments" on classical fluids. I. Thermodynamical Properties of Lennard-Jones Molecules. Phys. Rev. 159, 98–103 (1967)Google Scholar
  62. 62.
    Hess, B.: P-LINCS: a parallel linear constraint solver for molecular simulation. J. Chem. Theory Comput. 4, 116–122 (2008)CrossRefGoogle Scholar
  63. 63.
    Campbell, S., Rodgers, M.T., Marzluff, E.M., Beauchamp, J.L.: Deuterium exchange reactions as a probe of biomolecule structure. fundamental studies of gas phase H/D exchange reactions of protonated glycine oligomers with D2O, CD3OD, CD3CO2D, and ND3. J. Am. Chem. Soc. 117, 12840–12854 (1995)CrossRefGoogle Scholar
  64. 64.
    Ausloos, P., Lias, S.G.: Thermoneutral isotope-exchange reactions of cations in the gas phase. J. Am. Chem. Soc. 103, 3641–3647 (1981)CrossRefGoogle Scholar
  65. 65.
    Gard, E., Green, M.K., Bregar, J., Lebrilla, C.B.: Gas-phase hydrogen/deuterium exchange as a molecular probe for the interaction of methanol and protonated peptides. J. Am. Soc. Mass Spectrom. 5, 623–631 (1994)CrossRefGoogle Scholar
  66. 66.
    Wyttenbach, T., Bowers, M.T.: Gas phase conformations of biological molecules: the hydrogen/deuterium exchange mechanism. J. Am. Soc. Mass Spectrom. 10, 9–14 (1999)CrossRefGoogle Scholar
  67. 67.
    Evans, S.E., Lueck, N., Marzluff, E.M.: Gas phase hydrogen/deuterium exchange of proteins in an ion trap mass spectrometer. Int. J. Mass Spectrom. 222, 175–187 (2003)CrossRefGoogle Scholar
  68. 68.
    Winkler, H.D.F., Dzyuba, E.V., Sklorz, J.A.W., Beyeh, N.K., Rissanen, K., Schalley, C.A.: Gas-phase H/D-exchange reactions on resorcinarene and pyrogallarene capsules: proton transport through a one-dimensional Grotthuss mechanism. Chem. Sci. 2, 615–624 (2011)CrossRefGoogle Scholar
  69. 69.
    Hunter, E.P.L., Lias, S.G.: Evaluated gas phase Basicities and proton affinities of molecules: an update. J. Phys. Chem. Ref. Data. 27, 413–656 (1998)CrossRefGoogle Scholar
  70. 70.
    Zhang, J., Brodbelt, J.S.: Gas-phase hydrogen/deuterium exchange and conformations of deprotonated flavonoids and gas-phase acidities of flavonoids. J. Am. Chem. Soc. 126, 5906–5919 (2004)CrossRefGoogle Scholar
  71. 71.
    Tian, Z., Reed, D.R., Kass, S.R.: H/D exchange pathways: Flip-flop and relay processes. Int. J. Mass Spectrom. 377, 130–138 (2015)CrossRefGoogle Scholar
  72. 72.
    Reid, G.E., O’Hair, R.A.J., Styles, M.L., McFadyen, W.D., Simpson, R.J.: Gas phase ion–molecule reactions in a modified ion trap: H/D exchange of non-covalent complexes and coordinatively unsaturated platinum complexes. Rapid Commun. Mass Spectrom. 12, 1701–1708 (1999)CrossRefGoogle Scholar
  73. 73.
    Reyzer, M.L., Brodbelt, J.S.: Gas-phase H/D exchange reactions of polyamine complexes: (M + H)+, (M + alkali metal+), and (M + 2H)2+. J. Am. Soc. Mass Spectrom. 11, 711–721 (2000)CrossRefGoogle Scholar
  74. 74.
    Kaltashov, I.A., Vladimir, D.M., Cotter, R.J.: Gas phase hydrogen/deuterium exchange reactions of peptide ions in a quadrupole ion trap mass spectrometer. Proteins: structure. Function, and Bioinformatics. 28, 53–58 (1997)CrossRefGoogle Scholar
  75. 75.
    Solouki, T., Fort, R.C., Alomary, A., Fattahi, A.: Gas phase hydrogen deuterium exchange reactions of a model peptide: FT-ICR and computational analyses of metal induced conformational mutations. J. Am. Soc. Mass Spectrom. 12, 1272–1285 (2001)CrossRefGoogle Scholar
  76. 76.
    Kostiainen, R., Kauppila, T.J.: Effect of eluent on the ionization process in liquid chromatography–mass spectrometry. J. Chromatogr. A. 1216, 685–699 (2009)CrossRefGoogle Scholar
  77. 77.
    Kebarle, P., Verkerk Udo, H.: Electrospray: from ions in solution to ions in the gas phase, what we know now. Mass Spectrom. Rev. 28, 898–917 (2009)CrossRefGoogle Scholar
  78. 78.
    Zhou, S., Cook, K.D.: Probing solvent fractionation in electrospray droplets with laser-induced fluorescence of a Solvatochromic dye. Anal. Chem. 72, 963–969 (2000)CrossRefGoogle Scholar
  79. 79.
    Lu, H.M., Jiang, Q.: Size-dependent surface tension and Tolman's length of droplets. Langmuir. 21, 779–781 (2005)CrossRefGoogle Scholar
  80. 80.
    Kashiwagi, T., Yamada, N., Hirayama, K., Suzuki, C., Kashiwagi, Y., Tsuchiya, F., Arata, Y., Kunishima, N., Morikawa, K.: An electrospray-ionization mass spectrometry analysis of the pH-dependent dissociation and denaturation processes of a heterodimeric protein. J. Am. Soc. Mass Spectrom. 11, 54–61 (2000)CrossRefGoogle Scholar
  81. 81.
    Wang, R., Zenobi, R.: Evolution of the solvent polarity in an electrospray plume. J. Am. Soc. Mass Spectrom. 21, 378–385 (2010)CrossRefGoogle Scholar
  82. 82.
    Banerjee, S., Mazumdar, S.: Electrospray ionization mass spectrometry: a technique to access the information beyond the molecular weight of the Analyte. Int. J. Anal. Chem. 2012, 282574 (2012)CrossRefGoogle Scholar
  83. 83.
    Li, Z., Li, L.: Chemical-vapor-assisted electrospray ionization for increasing Analyte signals in electrospray ionization mass spectrometry. Anal. Chem. 86, 331–335 (2014)CrossRefGoogle Scholar
  84. 84.
    Schmidt, A., Karas, M., Dülcks, T.: Effect of different solution flow rates on analyte ion signals in nano-ESI MS, or: when does ESI turn into nano-ESI? J. Am. Soc. Mass Spectrom. 14, 492–500 (2003)CrossRefGoogle Scholar
  85. 85.
    Thacker, J.B., Schug, K.A.: Effects of solvent parameters on the electrospray ionization tandem mass spectrometry response of glucose. Rapid Commun. Mass Spectrom. 32, 1191–1198 (2018)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Department of Chemistry & BiochemistryBaylor UniversityWacoUSA

Personalised recommendations