EP2710624B1 - Procédé et dispositif par électronébulisation d'un échantillon ou un solvant contenant l'échantillon - Google Patents

Procédé et dispositif par électronébulisation d'un échantillon ou un solvant contenant l'échantillon Download PDF

Info

Publication number
EP2710624B1
EP2710624B1 EP12732867.2A EP12732867A EP2710624B1 EP 2710624 B1 EP2710624 B1 EP 2710624B1 EP 12732867 A EP12732867 A EP 12732867A EP 2710624 B1 EP2710624 B1 EP 2710624B1
Authority
EP
European Patent Office
Prior art keywords
capillary
analyte
mass
spectrometer
capillaries
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
Application number
EP12732867.2A
Other languages
German (de)
English (en)
Other versions
EP2710624A1 (fr
Inventor
Anneli KRUVE
Koit HERODES
Rünno LÕHMUS
Ivo LEITO
Ants LÕHMUS
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tartu Ulikool (University of Tartu)
Estonian Nanotechnology Competence Centre
Original Assignee
Tartu Ulikool (University of Tartu)
Estonian Nanotechnology Competence Centre
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Tartu Ulikool (University of Tartu), Estonian Nanotechnology Competence Centre filed Critical Tartu Ulikool (University of Tartu)
Publication of EP2710624A1 publication Critical patent/EP2710624A1/fr
Application granted granted Critical
Publication of EP2710624B1 publication Critical patent/EP2710624B1/fr
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

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
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • H01J49/167—Capillaries and nozzles specially adapted therefor

Definitions

  • the present invention relates to mass spectrometry and electrospray-ionisation (ESI) source used in mass spectrometers to spray the analyte or effluent containing the analyte into mass spectrometer.
  • the invention relates to a novel method for spraying the analyte from ionisation source into mass spectrometer and a novel construction of the injector of the ionisation source, which ensures the formation of smaller droplets with more uniform size distribution of effluent comprising the analyte, which results in more efficient evaporation of the solvent, which in turn enables to enhance the sensitivity of the mass spectrometer and the stability of the results.
  • the same principle may also be applied to improve the two other ionisation sources - atmospheric-pressure chemical ionisation and atmospheric-pressure photoionisation.
  • Electrospray ionisation has been used for more than two decades as a solvent for entering various samples into the mass spectrometer. ESI conditions are mild, enabling also to analyse thermally unstable compounds.
  • the effluent is directed into a metal capillary.
  • This capillary is subject to high potential (2-5 kV) in terms of the input of mass spectrometer. Both positive and negative potentials could be applied to the capillary.
  • positive potential is applied to the capillary of the mass spectrometer.
  • the potential creates an electric field in the space of the ESI ionisation source. Due to the electric field, positive and negative ions are emitted from the surface of the droplets of the liquid exiting the capillary. If the electric field is sufficiently strong, positively charged droplet escapes the surface of the solution. Formation of charged droplets caused by the electric field is called electrospray.
  • E 0 2 ⁇ ⁇ ⁇ cos ⁇ ⁇ 0 ⁇ r c 1 / 2
  • ⁇ is the surface tension of the effluent
  • ⁇ is the Taylor cone angle
  • ⁇ 0 is dielectric constant of vacuum
  • r c is the radius of the metal capillary.
  • the voltage to be applied to the capillary V on is: V on ⁇ r c ⁇ cos ⁇ 2 ⁇ ⁇ 0 1 / 2 ⁇ ln 4 ⁇ d r c where d is the distance between the capillary end and the mass spectrometer (opposite electrode).
  • d is the distance between the capillary end and the mass spectrometer (opposite electrode).
  • the solvent of the analyte and distance of the capillary V on values are in the range of 2200 V (e.g. methanol) and 4000 V (water). [Kebarle 2009].
  • the droplet exiting the capillary forms the so-called Taylor cone, which in turn is sprayed due to the Coulombic forces into a uniform mist of tiny droplets (diameter ca 1 ⁇ m).
  • the radius R of the formed droplets and charge q thereof may be calculated as follows: R ⁇ V f ⁇ ⁇ K 1 / 3 q ⁇ 0.7 ⁇ 8 ⁇ ⁇ ⁇ ⁇ 0 ⁇ ⁇ ⁇ R 3 1 / 2 ⁇
  • V f is the flow rate of the analyte
  • K is the conductivity of the analyte
  • ⁇ is the dielectric constant of the effluent containing the analyte.
  • ESI chamber uses the heated gas flow blown by the mass spectrometer - the so-called drying gas.
  • This gas protects the mass spectrometer against the entry of neutral molecules and facilitates evaporation of solvent from the droplets formed in the course of electrospray.
  • Wortmann et al showed that the concentration of the analyte increases in the formation processes of smaller droplets from larger droplets by at least 100 times [Wortmann, 2006]. Furthermore, it has been demonstrated that evaporation of solvent and formation of smaller droplets may result in a considerable change in the composition of the solvent, mainly due to preferential evaporation of more volatile solvents [Wang, 2010].
  • the small droplets returned are also subject to analogous solvent evaporation and distribution into smaller droplets via Coulomb explosion upon exceeding the Rayleigh limit. This process is repeated until due to the density of charges the field on the surface of the droplet is so strong to give way to desorption of ions from the droplet surface to the gas phase. [(Fenn, 1989); (Pramanik, 2002)] It has been suggested that ion desorption from the surface of the droplets starts when the droplet radius has decreased below 10 nm [Kebarle, 2009].
  • Iribarne- Thomson model As well as ion evaporation model, which describes the formation of ions from smaller molecules. [(Fenn, 1989); (Pramanik, 2002)]
  • ESI is also capable for creating ions, including multiply charged ions, from very large molecules, e.g. proteins. These ions are formed according to the charge residue model. According to this model, droplets divide into smaller droplets until the entire solvent has evaporated and the remaining charged analyte is analysed using a mass-spectrometer. [Kebarle, 2000]
  • [E + ] is the concentration of ions of other substance contained in the analyte
  • P is the processing efficiency of ions in mass-spectrometer
  • f is the fraction of charges emitted from the capillary and turned into gas-phase ions.
  • k A and k E express relative efficiency with which A + and E + are turned into respective gas-phase ions. [(Iribarne, 1976); (Kebarle, 2009); (de Hoffmann, 2004)]
  • ESI also enables to analyse compounds, which, which are not charged in the effluent.
  • These companies can undergo ionisation with the addition of a proton, metal cation (Na + , K + ) or ammonium cation. Usually a proton is added. Protonation occurs in a greater extent in electrospray than it would in the effluent as a result of pH reduction, as additional charges are generated in the course of electrochemical process.
  • the mass-spectrometric signal of ions returned from protonation of analytes with high p K b value decreases with a reduction in p K b .
  • gas-phase proton affinity impacts on the generation of ions from analyte.
  • protonated water cluster can give a proton to the molecule of gaseous methanol, the proton affinity of which is greater than the proton affinity of water.
  • the analytes may be analysed using ESI mass-spectrometer only when the gas-phase basicity of the analyte is greater than that of the solvent.
  • pneumatically assisted ESI has also been applied, which is also known as ionspray.
  • the advantage of this system is the easier coupling with liquid chromatography.
  • Kostiainen et al [Kostiainen, 1994] demonstrated that ion current is lower for pneumatically assisted ESI than for ordinary ESI.
  • Maxwell et al [Maxwell, 2010] have shown that the shape of the end of the metal capillary used in ESI source has a strong impact on the strength of the mass-spectrometric signal.
  • the object of the present invention is firstly to develop a method how to decrease the size of the droplets of the analyte or the effluent containing the latter, which are sprayed from ionisation source into mass-spectrometer. Decreasing the droplet size in turn enables better ionisation of the analyte particles, resulting in increased sensitivity of the mass-spectrometer.
  • the invention is also aimed at providing such construction of the injector of the ionisation source, which enables to implement the method according to the invention in the ionisation source, which is used for spraying the analyte into mass-spectrometer.
  • the most critical features of the ESI source are sensitivity to the analyte content in the solution and insensitivity (robustness) to the remaining characteristics of the sample.
  • One of the most important characteristics for assessing robustness is the matrix effect.
  • Matrix effect is a change in the ionisation efficiency of analyte due to the influence of other sample components analysed therewith.
  • the matrix effect may cause both signal suppression and amplification, which may result in under- or overestimation of the analysis results, respectively.
  • Andrews et al found that the use of nanospray (decrease in the flow rate from 200 ⁇ l/min to 0.1 ⁇ l/min) prior to the ESI source increases the sensitivity of mass-spectrometer to 1000%. [Andrews, 2004]
  • the formation of smaller droplets leads to increased sensitivity and lower matrix effect. Therefore, the intensity achieved using ESI ionisation source would increase further by modifying the spraying process so that the dimensions (radius, diameter) of the created droplets would be smaller than in the earlier solutions.
  • the efficiency of electro-chemical reaction depends on the voltage applied to the electrode and the surface area of the latter. It is known that in ESI the metal capillary acts as one electrode, whereas the electrochemical reaction takes place at the end of the capillary.
  • the metal area of the end of the capillary should be increased on the account of the surface area of the electrode.
  • the system is supplemented with a capillary for directing an additional nebulising gas system. If such an additional capillary has been made from metal, and when the effluent containing the analyte is entered in the capillary, the additional capillary carrying the nebulising gas functions as an electrode by participating in generation of additional charges.
  • a method is provided, according to which the additional spray of nebulising gas is directed into the spray of analyte and effluent containing the latter, which results in a circular-done shaped spray of analyte or effluent containing the latter, which is between inner and other spray of nebulising gas.
  • a piping of three (or more) capillaries is provided and the main parameters of the construction are optimised. This invention has been used for experimentation with pesticides in terms of sensitivity, decision limit and matrix effect.
  • the construction according to the invention results in, for example, a unique combination of electrospray-ionisation source spray, which provides the mass-spectrometer with better sensitivity and greater insensitivity to the rest of the features of the sample. It has been demonstrated earlier that by changing the parameters of ESI itself it is possible to increase robustness only on the account of sensitivity.
  • the method according to the invention comprises spraying the analyte or effluent comprising the analyte into mass-spectrometer and creating an outer jet of nebulising gas around it, and additional spraying of nebulising gas into the jet of the analyte or effluent containing the latter so that the jet of the analyte or effluent containing the latter is forced between the jets of two nebulising gases, i.e. the outer and inner jet, thus forming a circular-cone shaped jet of the analyte or effluent containing the latter.
  • Such a method also enables to use various nebulising gases, whereas if the outer nebulising gas is usually nitrogen, the inner nebulising gas may also be nitrogen or other inert gas, which is necessary for transporting the particles of the analyte into the mass-spectrometer.
  • the device according to the invention is an injector used, for example, in electrospray-ionisation source (ESI), which is designed for spraying the analyte or effluent comprising the latter from the ionisation source 1 to mass-spectrometer 2, where the sample is analysed.
  • EI electrospray-ionisation source
  • the device according to the invention which comprises a three-capillary system, may be used in various ionisation sources, for example, in atmospheric-pressure ionisation sources (APCI), atmospheric-pressure photoionisation sources (APPI), and the like.
  • APCI atmospheric-pressure ionisation sources
  • APPI atmospheric-pressure photoionisation sources
  • the injector 3, depicted in figure 5 comprises a system of capillaries, consisting of an external capillary A and the capillary B with the analyte, which has been placed inside the external capillary A.
  • One end of the external capillary A is connected with the source of nebulising gas 4.
  • One end of the analyte capillary B is connected with the source of analyte or effluent containing the latter 5 and through the space between the internal wall of the external capillary A and the external wall of the analyte capillary B the nebulising gas is directed into the injector 3, which sprays the gas into the mass-spectrometer.
  • the capillary system also comprises an additional inner capillary C, which is placed inside the capillary B comprising analyte.
  • the inner capillary C has been made of non-metal material, for example, quartz, but alternatively, it could also be made of metal or non-metal material, in which the external surface of the inner capillary is covered with metal making the inner capillary conductive.
  • the potentials of the inner capillary (C) and the analyte capillary (B) are equal.
  • the potentials of capillaries (C) and (B) differ from that of the mass-spectrometer. Thus, if necessary, better ionisation of analyte particles is possible.
  • One end of the inner capillary C is connected with the nebulising gas source 6, which may be the same nebulising gas source 4, which feeds the nebulising gas to external capillary A, but the presence of more than one source of nebulising gas enables to use different nebulising gases in the experiments.
  • the nebulising gas source 6 which may be the same nebulising gas source 4, which feeds the nebulising gas to external capillary A, but the presence of more than one source of nebulising gas enables to use different nebulising gases in the experiments.
  • the nebulising gas is directed via the inner capillary C into the injector, where the nebulising gas is sprayed into the jet 15 of the analyte or the effluent containing the latter, which results in forcing the analyte spray 15 between the two, external 14 and inner spray 16 of nebulising gas (the external jet 14 exits the injector 3 via the space formed between capillary A and the analyte capillary B and the internal jet 16 exits the injector 3 from the inner capillary C) so that the analyte jet has a circular cross-section (see figure 5 ).
  • the outlets of the capillaries on the side of the mass-spectrometer are aligned.
  • outlets of the capillaries may be shifted axially from one another so that, for example, the jet of the analyte coming out of the injector 3 via the space between the inner capillary C and the analyte capillary B would not mix immediately with the nebulising gas jet coming via the space between the external capillary and the analyte capillary B, thus the analyte capillary B has been moved outwards from the end of the external capillary in the injector 3.
  • the analyte capillary houses an additional number of inner capillaries (C), which form a capillary bundle and the inlet of which has been connected with the nebulising gas source and the outlet of which is for spraying the nebulising gas into the spray of the analyte or effluent containing the latter.
  • C inner capillaries
  • the inner capillaries are arranged in such a manner that the nebulising gas could be directed into the analyte or effluent containing the latter uniformly via all inner capillaries (C) or sequentially by the capillaries, which enables even more efficient breaking of the effluent spray so that the ions of the analyte of a very small quantity would reach the inlet of the mass-spectrometer.
  • the outlets of all the inner capillaries (C) in the bundle are aligned or shifted slightly with respect to one another.
  • the nebulising gas is sprayed from the inner capillaries (C) into the jet of the analyte and the mass-spectrometer from the inner capillaries continuously or sequentially by capillaries.
  • the testing device was constructed from three stainless-steel capillaries with the inner and outer diameter 4 and 2 mm, 0.8 and 0.55 mm and 0.203 and 0.089 mm, respectively. These capillaries are below referred to as capillaries A, B and C respectively.
  • the positions of capillary A and capillary B are fixed.
  • the length of capillary A was 53 mm, and the extension of capillary B from inside capillary A was 0.27 mm (i.e. 1/3 of its outer diameter).
  • the capillary C was removable and its length in relation to capillary B may be modified.
  • the injector nozzle of the ionisation source is a system of capillaries or pipes, where the external capillary is connected with the nebulising gas source and the analyte capillary holds a number of inner capillaries directing the nebulising gas in the jet of the analyte.
  • This solution enables to feed the nebulising gas into the mass-spectrometer via inner capillaries continuously, or alternatively, sequentially via individual capillaries, which would further break the jet of the nebulising gas and the analyte ions would enter the mass-spectrometer.
  • the constructed ionisation source was compared with the conventionally available Agilent Inc. ESI ionisation source in terms of sensitivity, decision limit and the matrix effect.
  • the commercial source returned a higher increase in the calibration graph, but also a greater variability in accordance with the standard deviation the rise of the calibration curve.
  • the ratio of the curve and its standard deviation was comparable in both constructions - the commercially available device as well as that of the invention.
  • the matrix effects were examined using a commercially available source. Paired t-test revealed that the alternative ionisation source returned 100% closer %ME values that were statistically important. For imazalil, for example, the ionisation with commercially available source was suppressed by 49% in the sample on average. The device according to the invention gives the average suppression of 26%.
  • the samples used were purchased from the local market and their pesticide content was checked prior to use.
  • the extracts obtained after the sample preparation were enriched with the standard mix of pesticides.
  • the buffered QuEChERS method was used for sample preparation [Lehotay, 2005].
  • 15 g of homogenised sample was placed in 50 ml polyethylene centrifuge tube.
  • 15 ml 1% acetic acid in acetonitrile, 6 g anhydrous magnesium sulphate and 1.5 g anhydrous sodium acetate were added to the reaction.
  • the tube was shaken intensively for 1-2 minutes, whereafter the tube was spun at 300U-3100 p/min (900 ⁇ g) for 1-1.5 min.
  • From the upper extract layer 1-1.1 ml was subjected to further purification, and 15 ml was dried using a centrifuge tube, which contained 50 mg PSA sorbent and 150 mg anhydrous magnesium sulphate.
  • the tube was shaken intensively for 0.4-0.6 minutes, and spun thereafter at 3000-3100 p/min.
  • the extract was collected and enriched using a standard solution of pesticides.
  • capillary C was optimized in relation to the analyte capillary.
  • the optimisation was also carried out for the second and third construction.
  • Capillary positions (extension) - length L with respect to capillary B in figure 1 - were 0, 0.5 and 1.0 mm.
  • Optimisation was carried out in chromatographic conditions and the standard solution used contained pesticides at the concentration of 0.45-0.5 mg/kg.
  • capillary C for the second and third construction
  • L 1 mm
  • the liquid meniscus is already relatively stretched, and, in the third construction, the additional gas can no longer considerably impact on the spraying process.
  • the spraying is made more efficient, i.e. smaller droplets are formed.
  • the linear area was the smallest, being up to 0.01-1.5 mg/kg, 0.01-0.5 mg/kg, 0.01-0.9 mg/kg and 0.01-2.5 mg/kg for carbendazim, thiabendazole, imazalil and methiocarb, respectively.
  • the linear areas were 0.01-1.5 mg/kg, 0.01-1.5 mg/kg, 0.01-2.5 mg/kg and 0.01-2.5 mg/kg, respectively, thus slightly wider than in the first construction.
  • the linear areas were 0.01-1.5 mg/kg, 0.01-3.5 mg/kg, 0.01-1.5 mg/kg and 0.01-1.5 mg/kg respectively.
  • M + H + ⁇ - > MH + which depends on the excess protons in the solution.
  • the number of protons depends on the efficiency of counterion removal. Counterions were removed as a result of the electrochemical reaction at the metal-liquid boundary surface at the end of the capillary. Thus, it could be said that more counterions are removed when the metal-liquid boundary surface is larger - for example, as a result of addition of inner capillary C. Thus, more additional protons results in more protonated analyte molecules while the factor limiting the dynamic area is the lack of protons.
  • Table 2 shows that the lowest limits of detections were established for the third construction.
  • the droplet area is relatively small and the analytes have to compete with the matrix components for the droplet surface area.
  • the third ESI construction which enables the formation of smaller droplets, creating more droplet surface area, decreases the competition between the analyte and the matrix, resulting in formation of more gas-phase ions of the analyte.

Landscapes

  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Plasma & Fusion (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Claims (16)

  1. Le procédé pour l'électronébulisation d'un échantillon ou d'un solvant contenant l'échantillon de la source d'ionisation dans un spectromètre de masse ; ledit procédé comprenant l'électronébulisation de l'échantillon ou du solvant contenant l'échantillon dans le spectromètre de masse et la création d'un jet de gaz nébulisant extérieur autour dudit échantillon ou autour du solvant comprenant l'échantillon, caractérisé en ce que :
    a. dans le jet d'échantillon ou de solvant, une certaine quantité de gaz nébulisant intérieur est pulvérisée de la sorte que le jet (15) d'échantillon ou de solvant contenant l'échantillon se tienne en position entre le jet intérieur (16) et le jet extérieur (14) du gaz nébulisant et en ce que :
    b. un jet en forme de cône circulaire est formé dudit échantillon ou dudit solvant contenant l'échantillon.
  2. Le procédé selon la revendication 1, caractérisé en ce que le gaz nébulisant extérieur et le gaz nébulisant intérieur sont deux gaz différents.
  3. Le procédé selon la revendication 1, caractérisé en ce que pour l'éléctronébulisation de l'échantillon ou du solvant contenant l'échantillon dans le spectromètre de masse, un système de capillaires est utilisé ; ledit système contient un capillaire extérieur pour le gaz nébulisant, un capillaire intermédiaire pour l'échantillon et au moins un capillaire intérieur pour le gaz nébulisant.
  4. Le procédé selon la revendication 3, caractérisé en ce que le gaz nébulisant intérieur est pulvérisé dans le jet d'échantillon ou du solvant contenant l'échantillon par un certain nombre de capillaires intérieurs.
  5. Le procédé selon la revendication 4, caractérisé en ce que le gaz nébulisant intérieur est pulvérisé dans le jet d'échantillon ou du solvant contenant l'échantillon simultanément et à partir de tous les capillaires intérieurs ou bien à des moments différents et à partir des capillaires différents.
  6. Le dispositif pour l'électronébulisation de l'échantillon ou du solvant contenant l'échantillon de la source d'ionisation (1) dans un spectromètre de masse (2) qui comprend
    - un injecteur (3) muni d'un système de capillaires comprenant un capillaire extérieur (A) et un capillaire intermédiaire (B) qui est placé dans le capillaire extérieur ; lesdits capillaires sont munis d'une sortie par laquelle l'échantillon ou le solvant contenant l'échantillon est pulvérisé dans le spectromètre de masse (2) ;
    - le capillaire extérieur (A), dont l'entrée est liée à la source de gaz nébulisant (4), et l'entrée du capillaire intermédiaire (B) sont liés à la source d'échantillon ou de solvant contenant l'échantillon (5), tandis que :
    - un espace est aménagé entre la paroi intérieure du capillaire extérieur (A) et la paroi extérieure du capillaire intermédiaire (B) ; ledit espace sert à diriger le gaz nébulisant dans le spectromètre de masse ; ledit dispositif est caractérisé en ce que :
    - dans le capillaire intermédiaire (B) se trouve au moins un capillaire intérieur (C) supplémentaire qui est muni d'entrée de gaz nébulisant, ladite entrée étant liée à la source de gaz nébulisant (6), ainsi que de sortie configurée pour la pulvérisation du gaz nébulisant dans le jet d'échantillon ou de solvant contenant l'échantillon (16) ; et en ce que
    - un espace est aménagé entre la paroi intérieure du capillaire intermédiaire (B) et la paroi extérieure du capillaire intérieur (C), ledit espace servant à diriger l'échantillon ou le solvant contenant l'échantillon dans le spectromètre de masse (2).
  7. Le dispositif selon la revendication 6, caractérisé en ce que les sorties de tous les capillaires (A, B, C) sont séparées par des intervalles égaux et se trouvent toutes dans la source d'ionisation.
  8. Le dispositif selon la revendication 6, caractérisé en ce que le capillaire intérieur (C) est placé dans le capillaire intermédiaire (B) de la sorte que la sortie du capillaire intérieur (C) s'étende de la coupe transversale plane du capillaire intermédiaire (B) et se dirige vers le spectromètre de masse.
  9. Le dispositif selon la revendication 6, 7 ou 8, caractérisé en ce que le capillaire intérieur (C) est composé d'un matériau non métallique.
  10. Le dispositif selon la revendication 6, 7 ou 8, caractérisé en ce que le capillaire intérieur (C) est composé d'un matériau métallique ou d'un matériau non métallique recouvert de métal.
  11. Le dispositif selon l'une quelconque des revendications précédentes 6-10, caractérisé en ce que le potentiel du capillaire intérieur (C) est différent du potentiel du capillaire intermédiaire (B) ainsi que du potentiel du spectromètre de masse.
  12. Le dispositif selon l'une quelconque des revendications précédentes 6-10, caractérisé en ce que le potentiel du capillaire intérieur (C) est égal au potentiel du capillaire intermédiaire (B), mais différent du potentiel du spectromètre de masse.
  13. Le dispositif selon la revendication 6, caractérisé en ce qu'un certain nombre de capillaires intérieurs (C) se trouve à l'intérieur du capillaire intermédiaire (B) ; lesdits capillaires forment un paquet de capillaires et sont liés à la source de gaz nébulisant (6) par l'entrée et par la sortie de la source pour pulvériser le gaz nébulisant dans le jet d'échantillon ou de solvant contenant l'échantillon (16).
  14. Le dispositif selon la revendication 13, caractérisé en ce que toutes les sorties de gaz nébulisant de tous les capillaires intérieurs (C) du paquet sont alignées.
  15. Le dispositif selon la revendication 13, caractérisé en ce que toutes les sorties de gaz nébulisant de tous les capillaires intérieurs (C) du paquet sont décalées les unes par rapports aux autres.
  16. Le dispositif selon la revendication 13, caractérisé en ce que l'électronébulisation du gaz nébulisant par des capillaires intérieurs (C) dans le jet d'échantillon et dans le spectromètre de masse peut être continue ou consécutive selon la disposition des capillaires intérieurs.
EP12732867.2A 2011-04-27 2012-04-26 Procédé et dispositif par électronébulisation d'un échantillon ou un solvant contenant l'échantillon Not-in-force EP2710624B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EEP201100030A EE05649B1 (et) 2011-04-27 2011-04-27 Meetod ja seade uuritava aine v?i uuritavat ainet sisaldava kandevedeliku pihustamiseks ionisatsiooniallikast massispektromeetrisse
PCT/IB2012/000920 WO2012146979A1 (fr) 2011-04-27 2012-04-26 Procédé et dispositif pour pulvériser un échantillon ou un solvant contenant l'échantillon depuis une source d'ionisation vers un spectromètre de masse

Publications (2)

Publication Number Publication Date
EP2710624A1 EP2710624A1 (fr) 2014-03-26
EP2710624B1 true EP2710624B1 (fr) 2015-06-17

Family

ID=46465236

Family Applications (1)

Application Number Title Priority Date Filing Date
EP12732867.2A Not-in-force EP2710624B1 (fr) 2011-04-27 2012-04-26 Procédé et dispositif par électronébulisation d'un échantillon ou un solvant contenant l'échantillon

Country Status (3)

Country Link
EP (1) EP2710624B1 (fr)
EE (1) EE05649B1 (fr)
WO (1) WO2012146979A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE112015006840B4 (de) 2015-10-09 2024-06-27 Hitachi High-Tech Corporation Ionenanalysevorrichtung

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5879949A (en) 1995-11-22 1999-03-09 Board Of Supervisors Of Louisiana State University & Agricultural And Mechanical College Apparatus and method for rapid on-line electrochemistry and mass spectrometry
US5868322A (en) * 1996-01-31 1999-02-09 Hewlett-Packard Company Apparatus for forming liquid droplets having a mechanically fixed inner microtube
EP2260503B1 (fr) * 2008-04-04 2018-10-10 Agilent Technologies, Inc. Sources d'ions electrospray pour une ionisation améliorée

Also Published As

Publication number Publication date
EP2710624A1 (fr) 2014-03-26
WO2012146979A1 (fr) 2012-11-01
EE201100030A (et) 2012-12-17
EE05649B1 (et) 2013-04-15

Similar Documents

Publication Publication Date Title
US5828062A (en) Ionization electrospray apparatus for mass spectrometry
Covey et al. Liquid chromatography/mass spectrometry
Abian The coupling of gas and liquid chromatography with mass spectrometry
Gelpí Interfaces for coupled liquid‐phase separation/mass spectrometry techniques. An update on recent developments
US8921777B2 (en) Atmospheric pressure ion source by interacting high velocity spray with a target
Abian et al. Comparison of conventional, narrow‐bore and capillary liquid chromatography/mass spectrometry for electrospray ionization mass spectrometry: practical considerations
US7820966B2 (en) Mass spectrometer
Voyksner Atmospheric Pressure Ionization LC/M
US8637812B2 (en) Sample excitation apparatus and method for spectroscopic analysis
US20070023631A1 (en) Parallel sample handling for high-throughput mass spectrometric analysis
US9378938B2 (en) Reproducibility of impact-based ionization source for low and high organic mobile phase compositions using a mesh target
Bonvin et al. Evaluation of a sheathless nanospray interface based on a porous tip sprayer for CE‐ESI‐MS coupling
US11029291B2 (en) Systems and methods for ionization
Banks Jr et al. [21] Electrospray ionization mass spectrometry
KR102483035B1 (ko) 다중 가스 흐름 이오나이저
US10020177B2 (en) Piezo-electric vibration on an in-source surface ionization structure to aid secondary droplet reduction
JP5219274B2 (ja) 質量分析計
EP2710624B1 (fr) Procédé et dispositif par électronébulisation d'un échantillon ou un solvant contenant l'échantillon
CN102841127B (zh) 一种等压双电离源接口及液相色谱-质谱联用仪
JP4164569B2 (ja) 質量分析等に用いるジェット流放電大気圧イオン化方法
JP2003217503A (ja) 質量分析装置及び質量分析方法
JP2017215317A (ja) エレクトロスプレーを増強する方法
US9437398B2 (en) Continuously moving target for an atmospheric pressure ion source
Bruins LC-MS and LC-MS-MS for Biomedical Analyses
Higton et al. Mass spectrometry: pharmaceutical sciences

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20131126

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAX Request for extension of the european patent (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

INTG Intention to grant announced

Effective date: 20150105

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 732336

Country of ref document: AT

Kind code of ref document: T

Effective date: 20150715

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602012008076

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150917

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 732336

Country of ref document: AT

Kind code of ref document: T

Effective date: 20150617

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

Ref country code: NL

Ref legal event code: MP

Effective date: 20150617

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150918

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150917

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: RO

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20150617

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20151017

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20151019

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602012008076

Country of ref document: DE

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 5

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

26N No opposition filed

Effective date: 20160318

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160430

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20160426

Ref country code: BE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160430

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160430

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 6

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160426

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 7

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20120426

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

Ref country code: MT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20160430

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20180423

Year of fee payment: 7

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20180411

Year of fee payment: 7

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20150617

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20180411

Year of fee payment: 7

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 602012008076

Country of ref document: DE

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20190426

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20190426

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20191101

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20190430