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WO2017168167A1 - Ionisation de molécules et appareil d'ionisation par électro-nébulisation - Google Patents

Ionisation de molécules et appareil d'ionisation par électro-nébulisation Download PDF

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Publication number
WO2017168167A1
WO2017168167A1 PCT/GB2017/050914 GB2017050914W WO2017168167A1 WO 2017168167 A1 WO2017168167 A1 WO 2017168167A1 GB 2017050914 W GB2017050914 W GB 2017050914W WO 2017168167 A1 WO2017168167 A1 WO 2017168167A1
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WIPO (PCT)
Prior art keywords
ions
jet
chamber
source
molecules
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PCT/GB2017/050914
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English (en)
Inventor
Peter O'connor
Chris WOOTTON
Haytham Hussein
Cookson CHIU
Man Ying WONG
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The University Of Warwick
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Publication of WO2017168167A1 publication Critical patent/WO2017168167A1/fr

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Classifications

    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/14—Ion sources; Ion guns using particle bombardment, e.g. ionisation chambers
    • H01J49/145—Ion sources; Ion guns using particle bombardment, e.g. ionisation chambers using chemical ionisation
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J27/00—Ion beam tubes
    • H01J27/02—Ion sources; Ion guns
    • H01J27/20—Ion sources; Ion guns using particle beam bombardment, e.g. ionisers
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/107—Arrangements for using several ion sources
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation

Definitions

  • This invention relates to a method of ionising molecules, and electrospray ionisation apparatus.
  • Mass spectrometry is a well-known technique, in which molecules can be characterised based upon their mass to charge ratio. However, in order to identify neutral molecules, it is first necessary to ionise them, so that they have a charge and so can be characterised.
  • ESI electrospray ionisation
  • a solution of molecules in a solvent is passed through a nozzle which is raised to a potential difference relative to a target.
  • a charge is transferred onto the solution as it exits the nozzle tip and, with judicious choice of solvent, preferentially retained on the molecules (which are of interest) rather than the solvent (which is of little interest) .
  • charge can be transferred onto a molecule .
  • Electrospray ionisation is referred to as nanoESI (or nano-ESI) when the nozzle has a very fine tip.
  • nanoESI Electrospray ionisation
  • the nozzle typically has a diameter of less than ⁇ ⁇ and is usually made from pulled glass capillaries.
  • CI Chemical ionisation
  • CH 5 + cation is considered a "super-acid" as it has an extremely low proton affinity, even lower than that of sulfuric acid (53 1.4 vs. 699.6 kJ/mol, respectively).
  • CH 5 + was first introduced as an ionization reagent by Munson and Field, 1966, (Munson, M. S . B .; Field, F. H. J. Am. Chem. Soc. 1966, 88, 2621-2630 and Field, F. H. ; Munson, M. S . B . J. Am. Chem. Soc. 1965, 87, 3289-3294).
  • CH 5 ions are the primary, stable reaction products from equations 1 &2 and are thus available for further reaction with target analytes.
  • CH 5 + ions act as extremely strong Bronsted acids (the so called “super-acids”) which readily transfer protons to nearby species, producing a protonated analyte species (M+H) + as shown Equation 3.
  • FTMS Fourier Transform Mass Spectroscopy
  • FT-ICR MS Fourier Transform Ion Cyclotron Resonance Mass Spectrometer
  • Enhancing the charge state enables a higher degree of fragmentation, thus more molecular sequence information, which is critical for effective identification of unknown proteins and peptides via MS/MS fragmentation and the analysis of any proteomic-based sample. Studies of post-translational modifications could also be facilitated by this increase in fragmentation efficiency, especially in the ever-growing field of Top-Down MS/MS .
  • Atmospheric pressure chemical ionisation is a similar technique to CI.
  • the analyte in solution in entrained in a flow of gas, typically nitrogen (N 2 ).
  • N 2 nitrogen
  • the sample in solution is then passed over a spark, which ionises the background air molecules and residual solvent, which then reacts with the analyte to increase the charge thereon.
  • a method of ionising molecules comprising:
  • the CH 5 + ion can be used to supercharge molecules that have been subject to electrospray treatment, in particular electrospray ionisation.
  • electrospray ionisation Typically, as the jet leaves the electrospray emitter it will pass through a first region in which the jet is unfragmented and then a second region in which the jet fragments into droplets; as such, the flow may pass over the jet in the first region.
  • the method would also comprise the creation of the CH 5 + ions, typically in a source of CH 5 + ions.
  • this would comprise passing methane (CH 4 ) over an electrical arc or another source of electrons such as a hot filament, electron emitter, photoemission of electrons from molecules or surfaces by interaction with light, or a plasma created by heating, including use of an inductively coupled resonance plasma.
  • the electrospray emitter and the source of CH 5 + ions may be provided within a chamber.
  • the method may comprise removing oxygen from the chamber, typically before CH 5 + ions are created. This has the advantage that the method can then be carried out at atmospheric pressure, as there will be no combustion of the methane with the oxygen, which could lead to catastrophic failure of the chamber.
  • the chamber may be sealed against the ingress of oxygen, at least after the oxygen is removed.
  • the oxygen may be removed until at most 5%, 3%, 2% or 1 % of the gas within the chamber is oxygen.
  • the oxygen may be removed by flushing the chamber with a gas which does not comprise oxygen (for example, nitrogen gas) .
  • the method may comprise reacting the oxygen, for example by controlled combustion or using an oxygen scavenger.
  • the chamber may be at atmospheric pressure, typically 1 atm ( 101.325 kPa) to within 10%, 5 %, 2% or 1 %. This has not been possible (or even contemplated) with prior art chemical ionisation techniques using CH 5 + .
  • the pressure within the chamber may be higher than atmospheric pressure (e.g. two or three times atmospheric pressure), or lower than atmospheric pressure (e .g. up to or approaching a pure vacuum) .
  • the solution may comprise a solvent, which may be water, methanol, acetonitrile, acetone, hexane, or any other convenient solvent with a proton affinity greater than the chemical ionization reagent gas, typically methane .
  • a solvent which may be water, methanol, acetonitrile, acetone, hexane, or any other convenient solvent with a proton affinity greater than the chemical ionization reagent gas, typically methane .
  • the method may comprise flowing a sheath gas over the jet as it exits the electrospray emitter; typically, the sheath gas may be a relative inert gas (e.g. compared to oxygen), such as nitrogen (N 2 ).
  • the sheath gas may improve the nebulization of the jet (i.e. the fragmentation of the jet into droplets) and/or the evaporation of the solvent.
  • there may be no sheath gas passed over the jet and the flow of CH 5 + ions may pass over the jet without having to pass through a flow of sheath gas.
  • the flow may be produced substantially orthogonally to the jet; optionally, the flow may be within 15, 10 or 5 degrees of orthogonal, or the flow may be collinear with the jet.
  • the molecules are likely to be molecules, such as proteins, DNA, RNA, oligosaccharides, polymers, lipids, or organic and inorganic molecules.
  • the method may comprise passing the jet (which may have fragmented into droplets) to a mass spectrometry device after the flow has passed over it.
  • the method may comprise carrying out mass spectrometry on the jet.
  • an electrospray ionisation apparatus comprising:
  • an electrospray emitter within the chamber provided with a potential difference source so as to provide a potential difference between the electrospray emitter and a housing of the emitter such that when a solution containing molecules is introduced to the electrospray emitter with the potential difference applied, a jet of solution is emitted from the electrospray emitter;
  • CH 5 + ion can be used to supercharge molecules that have been subject to electrospray treatment, in particular electrospray ionisation.
  • the electrospray emitter may comprise a tip where the jet is emitted from the electrospray emitter and, typically, as the jet leaves the electrospray emitter it will pass through a first region in which the jet is unfragmented and then a second region in which the jet fragments into droplets; the source of CH 5 + ions may be positioned sufficiently close to the tip such that the flow passes over the jet in the first region. It will generally be preferred that the CH 5 + ions are allowed to react with the jet both before and while it fragments. When the jet fragments into positively charged droplets, the coulombic repulsion between the ions and the droplets will increase causing a decrease in the fraction of ions which have sufficient kinetic energy to approach the droplet.
  • the source of CH 5 + ions may comprise an arc creation device (such as a needle raised to a high potential difference relative to a body) over which methane can be passed; the apparatus may then be provided with a source of methane (such as a bottle thereof).
  • the source of CH 5 + ions could be a reaction of the methane gas with any source of electrons.
  • the source may comprise a hot filament and/or an electron emitter over which methane can be passed.
  • Other sources may include a light source which may result in photoemission of electrons from molecules or surfaces due to interaction with the emitted light.
  • the apparatus may comprise a means for heating the CH 5 + ions, such as a heater or plasma generated by photons or inductive coupled heating.
  • the apparatus may comprise means for removing oxygen from the chamber. This has the advantage that the method can then be carried out at atmospheric pressure, as there will be no combustion of the methane with the oxygen, which could lead to catastrophic failure of the chamber.
  • the chamber may be sealed against the ingress of oxygen, at least after the oxygen is removed.
  • the oxygen may be removed by flushing the chamber with a flushing gas which does not comprise oxygen (for example, nitrogen gas); as such, the means for removing oxygen may comprise a pair of ports for introducing and release the flushing gas, and/or a source of the flushing gas. Alternatively or additionally, the means for removing the oxygen may comprise means for reacting the oxygen, for example a controlled combustion device or an oxygen scavenger.
  • the apparatus may be provided with an oxygen sensor, so as to determine when the oxygen level is sufficiently low as to allow the generation of CH 5 + ions.
  • the chamber may be at atmospheric pressure, typically 1 atm ( 101.325 kPa) to within 10%, 5%, 2% or 1 %. This has not been possible (or even contemplated) with prior art chemical ionisation techniques using CH 5 + .
  • the apparatus may comprise a source for a flow of a sheath gas over the jet as it exits the electrospray emitter; typically, the sheath gas may be a relative inert gas, such as nitrogen (N 2 ). Alternatively, there may be no sheath gas passed over the jet, and the flow of CH 5 + ions may pass over the jet without having to pass through a flow of sheath gas.
  • the molecules are likely to be large molecules, such as proteins, DNA, RNA, oligosaccharides, polymers, lipids, or organic and inorganic molecules .
  • the chamber may be provided with a port for allowing the jet to leave the chamber; typically, this would mate with a suitable mass spectrometry apparatus.
  • the apparatus may be used to carry out the method of the first aspect of the invention.
  • a method of ionising molecules comprising: • passing a solution comprising the molecules dissolved in a solvent through an electrospray emitter which has a potential difference applied thereto relative to a housing of the emitter, in order to create a jet of solution; and
  • Typical ions for the flow of ions could include protonated ions of methane (e.g. CH 5 + ions) or ions of other gases such as ethane, acetylene, acetone, or any other ions which have a lower proton affinity than the solvent molecules in the solution.
  • methane e.g. CH 5 + ions
  • ions of other gases such as ethane, acetylene, acetone, or any other ions which have a lower proton affinity than the solvent molecules in the solution.
  • the electrospray emitter and a source of the flow of ions may be provided within a chamber.
  • the pressure within the chamber may be at atmospheric pressure, typically 1 atm ( 101.325 kPa) to within 10%, 5%, 2% or 1 %.
  • the pressure within the chamber may be higher than atmospheric pressure (e.g. two, or three or more times atmospheric pressure), or lower than atmospheric pressure (e.g. up to or approaching a pure vacuum).
  • the method may have any of the optional features of the first aspect of the invention, in which the reference to the CH 5 + ions are replaced by a reference to the ions having a lower proton affinity.
  • an electrospray ionisation apparatus comprising:
  • an electrospray emitter within the chamber provided with a potential difference source so as to provide a potential difference between the electrospray emitter and a housing of the emitter such that when a solution comprising molecules dissolved in a solvent is introduced to the electrospray emitter with the potential difference applied, a jet of solution is emitted from the electrospray emitter;
  • a source of ions within the chamber arranged to emit a flow of ions; in which the source of ions is positioned so as to pass the flow over the jet and in which the ions have a lower proton affinity than molecules of the solvent.
  • the apparatus may have any of the optional features of the second aspect of the invention, in which the reference to the CH 5 + ions are replaced by a reference to the ions having a lower proton affinity than the molecules of the solvent.
  • Typical ions for the flow of ions could include protonated ions of methane (e.g. CH 5 + ions) or ions of other gases such as ethane, acetylene, acetone, or any other ions which have a lower proton affinity than the solvent molecules in the solution.
  • methane e.g. CH 5 + ions
  • ions of other gases such as ethane, acetylene, acetone, or any other ions which have a lower proton affinity than the solvent molecules in the solution.
  • Figure 1 shows a cross section through an electrospray ionisation apparatus in accordance with an embodiment of the invention
  • Figure 2 shows a perspective exploded view of the apparatus of Figure 1 ;
  • Figure 3 shows a schematic view of the emission of a jet of fluid within the apparatus of Figure 1 ;
  • Figure 4 shows an enlarged view of Figure 4; and Figures 5 to 8 each show a pair of mass spectrometry spectra showing the effect of using the apparatus of the embodiment of Figure 1.
  • the embodiments described below utilize the possibility of enhancing the charging, i.e. supercharging, through a direct reaction between methane super-acid, i.e. CH 5 + ions (Bronsted acid), with the sprayed solution droplets of an analyte at atmospheric pressure during the electrospray ionisation (ESI) process.
  • methane super-acid i.e. CH 5 + ions (Bronsted acid)
  • CH 5 + "super-acid ions” are ideal species for exploring the combination of ESI and gas-phase supercharging via APCI generated reagent ions.
  • Enhanced droplet charge translates to increased protonation of charge sites in proteins and increased intensity and/or higher observed charge states of analyte species.
  • FIG. 1 and 2 of the accompanying drawings An electrospray ionisation apparatus in accordance with an embodiment of the invention is shown in Figures 1 and 2 of the accompanying drawings.
  • the apparatus comprises a chamber 2 into which a copper/brass sheath 3 extends.
  • a brass sheath 3 may be used.
  • the sheath has a passage 4 therewithin through which a solution comprising a solvent and molecules of an analyte can pass.
  • the passage 4 terminates at a tip 5 of the sheath 3 where the passage 4 is open into the chamber.
  • a potential difference can be applied between the sheath 3 and the frame of the instrument.
  • the sheath 3 therefore forms an electrospray ionisation (ESI) needle .
  • ESI electrospray ionisation
  • the chamber is also provided with a source of CH 5 + ions 6.
  • a source of CH 5 + ions 6 This comprises a glow discharge chamber which comprises a cylindrical wall 7 and a central needle 8. Placing a DC voltage across the wall 6 and needle 8 will generate a spark 9.
  • the source 6 is also provided with a port 10 which allows the introduction of methane (CH 4 ) from outside of the chamber 2 into the source 6 so that it passes over the spark 9.
  • the chamber is also provided with a port 1 1 for the introduction of a sheath gas (e.g. Nitrogen (N 2 )) into the chamber. It also includes a one-way pressure relief valve 13 , which will actuate to relieve the pressure in the chamber if it is more than 5 psi (34 kPa) above local atmospheric pressure .
  • a sheath gas e.g. Nitrogen (N 2 )
  • N 2 Nitrogen
  • a port 12 for connection to a mass spectrometry device .
  • the oxygen is purged from the chamber by flushing the chamber with the methane or sheath gas (e.g. Nitrogen) before the DC voltage is turned on.
  • the methane or sheath gas may be allowed to flow through the chamber for at least one minute before the DC voltage is turned on.
  • the super-acid CH 5 is produced by ionizing a stream of methane gas flowing through a potential difference region between the needle 8 and the walls 7.
  • the source 6 comprises a tailor-made threaded brass cylinder 7 isolated from both the sheath 3 and the needle 8 via insulating Teflon caps.
  • Nebulizing gas (Nitrogen) was introduced via the sheath gas port 1 1 surrounding the ESI needle 3, enabling effective ESI plume generation.
  • Analyte solution can be delivered to the ESI needle 3 via a 250 (microlitre) syringe connected to a transfer line and driven via a syringe pump at a rate of 100-200 ⁇ /hour.
  • the ESI needle was biased from +4000 to +6000 V to achieve stable ESI.
  • a voltage difference of +3500 V was applied to the glow discharge system via an external high-voltage power supply.
  • a cylindrical mesh (not shown) surrounded the ESI assembly and was held at positive potential to focus the ions, allowing the improved interaction between the generated super-acid CH 5 + and the sample solution in the gas phase and preventing charge build up on the source walls.
  • an aluminium flange connects the apparatus 1 to the inlet of the (in this embodiment) Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR) mass spectrometer.
  • FT-ICR Fourier Transform Ion Cyclotron Resonance Mass Spectrometer
  • the operation of the apparatus 1 can be demonstrated with respect to Figures 3 and 4 of the accompanying drawings.
  • the analyte 20 is introduced through the sheath 3 and exits the tip 5 surrounded by sheath gas (nitrogen) 21 to form a jet 23.
  • the flow 22 of CH 5 ions is introduced orthogonally to the jet 23 , but is carried along the jet 23 by sheath gas 21.
  • the solution is emitted from the tip 5 with a positive charge . This means that, as the solvent evaporates, the jet will tend to break up into finer and finer droplets 24.
  • the flow 22 is arranged to flow over the jet 23 before it disperses into droplets 24.
  • the effects of the flow can be seen in Figure 4.
  • the CH 5 + ions are shown surrounding a droplet 24. They approach the droplet (the Coulombic repulsion not yet being insurmountable) and donate protons to the droplet, leaving as methane (CH 4 ) molecules 26.
  • the droplets are therefore supercharged; as the solvent evaporates, the charge donated by the CH 5 + ions will preferentially be retained on the analyte molecules.
  • Ions were externally accumulated in a hexapole collision cell for 0. 1 -0.2 s before being transferred to an infinity cell (e.g. an Ion Cyclotron Resonance trap) for excitation and detection.
  • an infinity cell e.g. an Ion Cyclotron Resonance trap
  • An example of an infinity cell is disclosed in Caravatti, P., Allemann, M., RF Shim by Trap Segmentation, Org. Mass Spectrom, 1991, 26, 5 14-5 18.
  • Bovine heart Cytochrome C chicken egg-white Lysozyme, and Equine heart Myoglobin were obtained from Sigma-Aldrich, UK.
  • the samples were prepared by dissolving the proteins in solvent system that consists of either purified water 18 ⁇ cm "1 only or 50/50 %, V/V water/methanol.
  • Methane reagent gas was purchased from CK special gases (UK) .
  • L-(+)-ascorbic acid (C 6 H 8 0 6 ) was purchased from Alfa Aesar, Heysham, Lancashire, UK. High purity grade N 2 (99.99 % BOC, UK) was used as the nebulizer gas for ESI and APCI-ESI experiments.
  • Ultrapure water ( 18.2 ⁇ cm “1 ) was obtained from a Direct-Q water purification unit (Millipore, Watford, UK) and LC-MS grade methanol (VWR Chemicals, UK) were used in the sample preparation. All reagents were used as received.
  • Figure 5a shows the measured MS spectrum of ⁇ ⁇ Lysozyme dissolved in water, a very narrow range of charge states was observed (8 + , 9 + , and 10 + ).
  • Figure 5b shows the same protein-containing solution ionized via the apparatus 1.
  • the supercharged lysozyme spectrum shows the 1 1+ charge state of the protein appearing in good intensity and a decrease of lower charge states (8 + and 9 + ), focusing ion populations into the higher charge states.
  • the weighted average charge state for each spectrum was calculated via equation 5 (below) where N is the number of observed charge states i th , qi is the charge value and Wi is the signal intensity.
  • the calculations show a distinct increase in average charge from 9.41 (without the apparatus functioning) to 10.02 (with the apparatus functioning).
  • the incorporation of apparatus derived CH 5 + ions has clearly enhanced charging of the protein analyte species.
  • qaverage ⁇ qi Wi / ⁇ Wi [Eq. 5]
  • Figure 5 insets (a. 1 -3 and b. 1 -3) show the protonated lysozyme species from both the apparatus 1 non-functioning and the apparatus functioning spectra, along with the protonated species sodium adducts are observed.
  • the comparison of the two spectra shows that no change/modification of the analyte species has been observed (e.g. via methylation, CH 5 + adduction, or reaction with any other intermediates from equations 1 -5 (above)), the ionization method of this embodiment is shown to produce a similar distribution of protonated and sodium-adduct peaks, only with the benefit of enhanced charge states and with increased signal intensity.
  • Figure 6a and 6b show the apparatus-not-functioning and apparatus-functioning mass spectra respectively of denatured myoglobin (a 16.9 kDa oxygen transport protein) electrosprayed from a 50: 50 v/v water:methanol solution.
  • Denatured Myoglobin shows a range of charge states upon ESI-MS ranging from 10 to 17 ( Figure 6a).
  • the denatured myoglobin ionized via the apparatus 1 attained a much greater increase in charge states (see inset), previously unobtainable without supercharging.
  • Denaturation of Myoglobin causes loss of the non-covalently-bound Heme group, however ESI-MS does not show a detectable Heme species released.
  • the apparatus 1 shows increased signal of the [Heme] + ion released upon Myoglobin denaturation, allowing it to be detected.
  • the normal spectrum of denatured Myoglobin showed a weighted average charge of 14.5, a base charge state of 15 + , and a max charge state of 18 + .
  • the spectrum of Myoglobin using the apparatus showed an average charge of 16.7, a base charge of 17 + , and a maximum charge of 25 + .
  • this embodiment represents a new method of achieving these charge states without the addition of chemical additives to the sample solution, and thus avoiding unwanted side reactions/changes in chemical equilibria which can occur upon addition of new species to solution chemical mixtures.
  • use of this apparatus 1 requires no further sample preparation steps, unlike chemical additive-supercharging, as each sample is simply introduced in the same way as a normal ESI-MS sample.
  • Native-MS There is an increasing interest in attempting to retain protein structure during ionization and mass spectrometry analysis, the so-called Native-MS method.
  • Native MS attempts to keep proteins analytes folded in their solution conformation as much as possible during analysis, thus charge state distributions, surface labelling strategies (such as Hydrogen-Deuterium Exchange (HDX; see Katta, V.; Chait, B . T., Hydrogen-Deuterium Exchange Electrospray-Ionization Mass-Spectrometry - a Method for Probing Protein Conformational-Changes in Solution.
  • HDX Hydrogen-Deuterium Exchange
  • small molecule ionization can vary greatly depending on the chemical nature of the groups within the analyte, with some (particularly non-polar) species being particularly difficult to ionize effectively via ESI.
  • Ascorbic acid C 6 H 8 0 6
  • Figure 8a and 8b show the spectra without and with the apparatus 1 of ascorbic acid.
  • the main species observed in the spectra of Ascorbic acid without using the apparatus 1 were the protonated and Sodiated forms of ascorbic acid ([C 6 H 8 0 6 +H] + and [C 6 H 8 0 6 +Na] + ), along with a high intensity peaks for the protonated and Sodiated Ascorbic acid dimer ([C 6 H 8 0 6 C 6 H 8 0 6 +H] + and [C 6 H 8 0 6 C 6 H 8 0 6 +Na] + ).

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Abstract

L'invention concerne un procédé et un appareil d'ionisation de molécules, le procédé consistant à faire passer une solution (20) contenant les molécules à travers un émetteur d'électro-nébulisation auquel une différence de potentiel est appliquée, afin de créer un jet (23) de solution ; à faire passer un flux d'ions CH5+ (22), ou d'autres ions ayant une affinité protonique inférieure à celle du solvant de la solution, sur le jet (23). Le procédé peut être exécuté dans une chambre (2), typiquement à pression atmosphérique, de laquelle l'oxygène a été évacué.
PCT/GB2017/050914 2016-04-01 2017-03-31 Ionisation de molécules et appareil d'ionisation par électro-nébulisation WO2017168167A1 (fr)

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CN118824836A (zh) * 2023-04-21 2024-10-22 中国科学院大连化学物理研究所 用于离子化的同轴纳升电喷雾大气压化学电离复合电离源
CN119446886A (zh) * 2024-09-23 2025-02-14 暨南大学 一种结合空气动力学透镜的萃取电喷雾离子源及其应用

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CN118824836A (zh) * 2023-04-21 2024-10-22 中国科学院大连化学物理研究所 用于离子化的同轴纳升电喷雾大气压化学电离复合电离源
CN119446886A (zh) * 2024-09-23 2025-02-14 暨南大学 一种结合空气动力学透镜的萃取电喷雾离子源及其应用

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