Nanopore ion sources deliver individual ions of amino acids and peptides directly into high vacuum.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 Sep 2024
04 Sep 2024
Historique:
received:
23
05
2022
accepted:
07
08
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
4
9
2024
Statut:
epublish
Résumé
Electrospray ionization is widely used to generate vapor phase ions for analysis by mass spectrometry in proteomics research. However, only a small fraction of the analyte enters the mass spectrometer due to losses that are fundamentally linked to the use of a background gas to stimulate the generation of ions from electrosprayed droplets. Here we report a nanopore ion source that delivers ions directly into high vacuum from aqueous solutions. The ion source comprises a pulled quartz pipette with a sub-100 nm opening. Ions escape an electrified meniscus by ion evaporation and travel along collisionless trajectories to the ion detector. We measure mass spectra of 16 different amino acid ions, post-translationally modified variants of glutathione, and the peptide angiotensin II, showing that these analytes can be emitted as desolvated ions. The emitted current is composed of ions rather than charged droplets, and more than 90% of the current can be recovered in a distant collector.
Identifiants
pubmed: 39231934
doi: 10.1038/s41467-024-51455-x
pii: 10.1038/s41467-024-51455-x
doi:
Substances chimiques
Amino Acids
0
Peptides
0
Ions
0
Angiotensin II
11128-99-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7709Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)
ID : HG012938
Informations de copyright
© 2024. The Author(s).
Références
Aebersold, R. & Mann, M. Mass-spectrometric exploration of proteome structure and function. Nature 537, 347–355 (2016).
pubmed: 27629641
doi: 10.1038/nature19949
Cole, R. B. Electrospray and MALDI Mass Spectrometry: Fundamentals, Instrumentation, Practicalities, and Biological Applications (John Wiley & Sons, 2011).
Fenn, J. B., Mann, M., Meng, C. K., Wong, S. F. & Whitehouse, C. M. Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64–71 (1989).
pubmed: 2675315
doi: 10.1126/science.2675315
Taylor, G. I. Electrically driven jets. Proc. R. Soc. London, Ser. A 313, 453–475 (1969).
doi: 10.1098/rspa.1969.0205
Kebarle, P. & Verkerk, U. H. Electrospray: from ions in solution to ions in the gas phase, what we know now. Mass Spectrom. Rev. 28, 898–917 (2009).
pubmed: 19551695
doi: 10.1002/mas.20247
Page, J. S., Kelly, R. T., Tang, K. & Smith, R. D. Ionization and transmission efficiency in an electrospray ionization—mass spectrometry interface. J. Am. Soc. Mass Spectrom. 18, 1582–1590 (2007).
pubmed: 17627841
doi: 10.1016/j.jasms.2007.05.018
Smith, R. D., Loo, J. A., Edmonds, C. G., Barinaga, C. J. & Udseth, H. R. New developments in biochemical mass spectrometry: electrospray ionization. Anal. Chem. 62, 882–899 (1990).
pubmed: 2194402
doi: 10.1021/ac00208a002
Wilm, M. & Mann, M. Analytical properties of the nanoelectrospray ion source. Anal. Chem. 68, 1–8 (1996).
pubmed: 8779426
doi: 10.1021/ac9509519
El-Faramawy, A., Siu, K. M. & Thomson, B. A. Efficiency of nano-electrospray ionization. J. Am. Soc. Mass Spectrom. 16, 1702–1707 (2005).
pubmed: 16095913
doi: 10.1016/j.jasms.2005.06.011
Hawkrdige, A. M. in Quantitative Proteomics (eds Eyers, C. E. & Gaskell, S. J.) Practical considerations and current limitations in quantitative mass spectrometry-based proteomics, Ch. 1, 3–25 (Royal Society of Chemistry, 2014).
Marginean, I., Page, J. S., Tolmachev, A. V., Tang, K. & Smith, R. D. Achieving 50% ionization efficiency in subambient pressure ionization with nanoelectrospray. Anal. Chem. 82, 9344–9349 (2010).
pubmed: 21028835
pmcid: 2982749
doi: 10.1021/ac1019123
Tang, K. & Smith, R. D. Physical/chemical separations in the break-up of highly charged droplets from electrosprays. J. Am. Soc. Mass Spectrom. 12, 343–347 (2001).
pubmed: 11281610
doi: 10.1016/S1044-0305(01)00222-7
Li, S. et al. An integrated platform for isolation, processing, and mass spectrometry-based proteomic profiling of rare cells in whole blood. Mol. Cell. Proteomics 14, 1672–1683 (2015).
pubmed: 25755294
pmcid: 4458728
doi: 10.1074/mcp.M114.045724
Callahan, N., Tullman, J., Kelman, Z. & Marino, J. Strategies for development of a next-generation protein sequencing platform. Trends Biochem. Sci. 45, 76–89 (2020).
pubmed: 31676211
doi: 10.1016/j.tibs.2019.09.005
Budnik, B., Levy, E., Harmange, G. & Slavov, N. Scope-ms: mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation. Genome Biol. 19, 1–12 (2018).
doi: 10.1186/s13059-018-1547-5
Kelly, R. T. Single-cell proteomics: progress and prospects. Mol. Cell. Proteomics 19, 1739–1748 (2020).
pubmed: 32847821
pmcid: 7664119
doi: 10.1074/mcp.R120.002234
Restrepo-Pérez, L., Joo, C. & Dekker, C. Paving the way to single-molecule protein sequencing. Nat. Nanotechnol. 13, 786–796 (2018).
pubmed: 30190617
doi: 10.1038/s41565-018-0236-6
Alfaro, J. A. et al. The emerging landscape of single-molecule protein sequencing technologies. Nat. Methods 18, 604–617 (2021).
pubmed: 34099939
pmcid: 8223677
doi: 10.1038/s41592-021-01143-1
Steinbock, L. J., Otto, O., Chimerel, C., Gornall, J. & Keyser, U. F. Detecting DNA folding with nanocapillaries. Nano Lett. 10, 2493–2497 (2010).
pubmed: 20515038
doi: 10.1021/nl100997s
Jordan, J. S., Xia, Z. & Williams, E. R. Tips on making tiny tips: Secrets to submicron nanoelectrospray emitters. J. Am. Soc. Mass Spectrom. 33, 607–611 (2022).
pubmed: 35157433
doi: 10.1021/jasms.1c00372
Liu, H. & Cao, G. Effectiveness of the young-laplace equation at nanoscale. Sci. Rep. 6, 1–10 (2016).
Maulbetsch, W. Nanopore Mass Spectrometry. Ph.D. thesis, https://repository.library.brown.edu/studio/item/bdr:792908/ (Brown University, 2018).
Higuera, F. Qualitative analysis of the minimum flow rate of a cone-jet of a very polar liquid. J. Fluid Mech. 816, 428–441 (2017).
doi: 10.1017/jfm.2017.111
Iribarne, J. V. & Thomson, B. A. On the evaporation of small ions from charged droplets. J. Chem. Phys. 64, 2287–2294 (1976).
doi: 10.1063/1.432536
Higuera, F. Model of the meniscus of an ionic-liquid ion source. Phys. Rev. E 77, 026308 (2008).
doi: 10.1103/PhysRevE.77.026308
Bush, J. et al. The nanopore mass spectrometer. Rev. Sci. Instrum. 88, 113307 (2017).
pubmed: 29195372
pmcid: 5707180
doi: 10.1063/1.4986043
Meister, A. & Anderson, M. E. Glutathione. Annu. Rev. Biochem. 52, 711–760 (1983).
pubmed: 6137189
doi: 10.1146/annurev.bi.52.070183.003431
Broniowska, K. A., Diers, A. R. & Hogg, N. S-nitrosoglutathione. Biochim. Biophys. Acta, Gen. Subj. 1830, 3173–3181 (2013).
doi: 10.1016/j.bbagen.2013.02.004
Mann, M. & Jensen, O. N. Proteomic analysis of post-translational modifications. Nat. Biotechnol. 21, 255–261 (2003).
pubmed: 12610572
doi: 10.1038/nbt0303-255
Caleman, C. & van der Spoel, D. Temperature and structural changes of water clusters in vacuum due to evaporation. J. Chem. Phys. 125, 154508 (2006).
pubmed: 17059273
doi: 10.1063/1.2357591
Sellberg, J. A. et al. Ultrafast x-ray probing of water structure below the homogeneous ice nucleation temperature. Nature 510, 381–384 (2014).
pubmed: 24943953
doi: 10.1038/nature13266
Smith, J. D., Cappa, C. D., Drisdell, W. S., Cohen, R. C. & Saykally, R. J. Raman thermometry measurements of free evaporation from liquid water droplets. J. Am. Chem. Soc. 128, 12892–12898 (2006).
pubmed: 17002384
doi: 10.1021/ja063579v
Romero-Sanz, I., Bocanegra, R., Fernandez De La Mora, J. & Gamero-Castano, M. Source of heavy molecular ions based on Taylor cones of ionic liquids operating in the pure ion evaporation regime. J. Appl. Phys. 94, 3599–3605 (2003).
doi: 10.1063/1.1598281
Kebarle, P. & Tang, L. From ions in solution to ions in the gas phase-the mechanism of electrospray mass spectrometry. Anal. Chem. 65, 972A–986A (1993).
Rayleigh, L. On the equilibrium of liquid conducting masses charged with electricity. Lond. Edinb. Philos. Mag. J. Sci. 14, 184–186 (1882).
doi: 10.1080/14786448208628425
Loscertales, I. & Fernández De La Mora, J. Experiments on the kinetics of field evaporation of small ions from droplets. J. Chem. Phys. 103, 5041–5060 (1995).
doi: 10.1063/1.470591
Konermann, L., Ahadi, E., Rodriguez, A. D. & Vahidi, S. Unraveling the mechanism of electrospray ionization. Anal. Chem. 85, 2–9 (2012).
pubmed: 23134552
doi: 10.1021/ac302789c
Magnani, M. & Gamero-Castaño, M. Energy barrier for ion field emission from a dielectric liquid sphere. Phys. Rev. E 105, 054802 (2022).
pubmed: 35706165
doi: 10.1103/PhysRevE.105.054802
Fenn, J. B. Ion formation from charged droplets: Roles of geometry energy and time. J. Am. Soc. Mass Spectrom. 4, 524–535 (1993).
Gamero-Castano, M. & Fernandez De La Mora, J. Direct measurement of ion evaporation kinetics from electrified liquid surfaces. J. Chem. Phys. 113, 815–832 (2000).
doi: 10.1063/1.481857
Luedtke, W. et al. Nanojets, electrospray, and ion field evaporation: Molecular dynamics simulations and laboratory experiments. J. Phys. Chem. A 112, 9628–9649 (2008).
pubmed: 18828572
doi: 10.1021/jp804585y
Kwan, V. & Consta, S. Conical shape fluctuations determine the rate of ion evaporation and the emitted cluster size distribution from multicharged droplets. J. Phys. Chem. A 126, 3229–3238 (2022).
pubmed: 35549274
doi: 10.1021/acs.jpca.2c02056
Harper, C. C., Brauer, D. D., Francis, M. B. & Williams, E. R. Direct observation of ion emission from charged aqueous nanodrops: effects on gaseous macromolecular charging. Chem. Sci. 12, 5185–5195 (2021).
pubmed: 34168773
pmcid: 8179642
doi: 10.1039/D0SC05707J
Hollerbach, A. et al. Sizing sub-diffraction limit electrosprayed droplets by structured illumination microscopy. Analyst 143, 232–240 (2018).
doi: 10.1039/C7AN01278K
Li, H., Allen, N., Li, M. & Li, A. Conducting and characterizing femto flow electrospray ionization. Analyst 147, 1071–1075 (2022).
pubmed: 35195636
doi: 10.1039/D1AN02190G
Báez Bolivar, E. G. et al. Submicron emitters enable reliable quantification of weak protein–glycan interactions by esi-ms. Anal. Chem. 93, 4231–4239 (2021).
pubmed: 33630563
doi: 10.1021/acs.analchem.0c05003
Lide, D. R. CRC Handbook of Chemistry and Physics Vol. 85 (CRC press, 2004).
Fitch, C. A., Platzer, G., Okon, M., Garcia-Moreno E, B. & McIntosh, L. P. Arginine: its pka value revisited. Prot. Sci. 24, 752–761 (2015).
doi: 10.1002/pro.2647
Mansoori, B. A., Volmer, D. A. & Boyd, R. K. ‘wrong-way-round’electrospray ionization of amino acids. Rapid Commun. Mass Spectrom. 11, 1120–1130 (1997).
doi: 10.1002/(SICI)1097-0231(19970630)11:10<1120::AID-RCM976>3.0.CO;2-Q
Ojakivi, M., Liigand, J. & Kruve, A. Modifying the acidity of charged droplets. ChemistrySelect 3, 335–338 (2018).
doi: 10.1002/slct.201702269
Prewett, P. D., Mair, G. L. R. & Thompson, S. P. Some comments on the mechanism of emission from liquid metal ion sources. J. Phys. D Appl. Phys. 15, 1339–1348 (1982).
doi: 10.1088/0022-3727/15/7/027
Lozano, P. C. Energy properties of an emi-im ionic liquid ion source. J. Phys. D Appl. Phys. 39, 126–134 (2005).
doi: 10.1088/0022-3727/39/1/020
Stimpson, B. P. & Evans, C. A. Electrohydrodynamic ionization mass spectrometry: Review of instrumentation mechanisms and applications. Journal of Electrostatics 5, 411–430 (1978).
Cook, K. D. Electrohydrodynamic mass spectrometry. Mass Spectrom. Rev. 5, 467–519 (1986).
doi: 10.1002/mas.1280050404
Yuill, E. M., Sa, N., Ray, S. J., Hieftje, G. M. & Baker, L. A. Electrospray ionization from nanopipette emitters with tip diameters of less than 100 nm. Anal. Chem. 85, 8498–8502 (2013).
pubmed: 23968307
doi: 10.1021/ac402214g
Vegiri, A. & Schevkunov, S. V. A molecular dynamics study of structural transitions in small water clusters in the presence of an external electric field. J. Chem. Phys. 115, 4175–4185 (2001).
doi: 10.1063/1.1388545
He, Z., Cui, H., Hao, S., Wang, L. & Zhou, J. Electric-field effects on ionic hydration: a molecular dynamics study. J. Phys. Chem. B 122, 5991–5998 (2018).
pubmed: 29750528
doi: 10.1021/acs.jpcb.8b02773
Gallud, X. & Lozano, P. C. The emission properties, structure, and stability of ionic liquid menisci undergoing electrically assisted ion evaporation. J. Fluid Mech. 933, A43 (2022).
doi: 10.1017/jfm.2021.988
Zhan, D., Rose, J. & Fenn, J. B. Solvation studies of electrospray ions—method and early results. J. Am. Soc. Mass Spectrom. 9, 1241–1247 (1998).
doi: 10.1016/S1044-0305(98)00107-X
Toyama, N., Kohno, J.-y, Mafuné, F. & Kondow, T. Solvation structure of arginine in aqueous solution studied by liquid beam technique. Chem. Phys. Lett. 419, 369–373 (2006).
doi: 10.1016/j.cplett.2005.12.013
Maulbetsch, W., Wiener, B., Poole, W., Bush, J. & Stein, D. Preserving the sequence of a biopolymer’s monomers as they enter an electrospray mass spectrometer. Phys. Rev. Appl. 6, 054006 (2016).
doi: 10.1103/PhysRevApplied.6.054006
Secchi, E. et al. Massive radius-dependent flow slippage in carbon nanotubes. Nature 537, 210–213 (2016).
pubmed: 27604947
pmcid: 5015706
doi: 10.1038/nature19315
Lozano, P. & Martinez-Sanchez, M. Ionic liquid ion sources: characterization of externally wetted emitters. J. Colloid Interface Sci. 282, 415–421 (2005).
pubmed: 15589547
doi: 10.1016/j.jcis.2004.08.132
Miller, C. E. Characterization of Ion Cluster Fragmentation in Ionic Liquid Ion Sources. Ph.D. thesis, https://dspace.mit.edu/handle/1721.1/122372 (Massachusetts Institute of Technology, 2019).
Gault, B. et al. Atom probe tomography. Nat. Rev. Methods Primers 1, 51 (2021).
doi: 10.1038/s43586-021-00047-w
Schwarz, T. et al. Field evaporation and atom probe tomography of pure water tips. Sci. Rep. 10, 20271 (2020).
pubmed: 33219263
pmcid: 7680140
doi: 10.1038/s41598-020-77130-x
Qiu, S. et al. Direct imaging of liquid–nanoparticle interfaces with atom probe tomography. J. Phys. Chem. C 124, 19389–19395 (2020).
doi: 10.1021/acs.jpcc.0c05504
Stuve, E. M. Ionization of water in interfacial electric fields: an electrochemical view. Chem. Phys. Lett. 519, 1–17 (2012).
doi: 10.1016/j.cplett.2011.09.040
Segreto, N. et al. Understanding the underlying field evaporation mechanism of pure water tips in high electrical fields. J. Phys. Chem. A 126, 5663–5671 (2022).
pubmed: 35972399
doi: 10.1021/acs.jpca.2c04163
Hart, T. W. Some observations concerning the s-nitroso and s-phenylsulphonyl derivatives of l-cysteine and glutathione. Tetrahedron Lett. 26, 2013–2016 (1985).
doi: 10.1016/S0040-4039(00)98368-0
Drachman, N., LePoitevin, M., Szapary, H., Wiener, B. & Derek, S. Replication data for: nanopore ion sources deliver individual ions of amino acids and peptides directly into high vacuum https://doi.org/10.7910/DVN/XQG6NJ (2024).
Stein, D., Vietorisz, J. & Drachman, N. Systems and methods for analysis of peptide photodissociation for single-molecule protein sequencing (U.S. Patent WO2023023231A1, Feb. 2023).