EP2691974B1 - Verfahren zur dielektrisch behinderten elektosprayionisierung von flüssigen proben und zur nachfolgenden massenspektrometrischen analyse der erzeugten probenionen - Google Patents
Verfahren zur dielektrisch behinderten elektosprayionisierung von flüssigen proben und zur nachfolgenden massenspektrometrischen analyse der erzeugten probenionen Download PDFInfo
- Publication number
- EP2691974B1 EP2691974B1 EP12717215.3A EP12717215A EP2691974B1 EP 2691974 B1 EP2691974 B1 EP 2691974B1 EP 12717215 A EP12717215 A EP 12717215A EP 2691974 B1 EP2691974 B1 EP 2691974B1
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- EP
- European Patent Office
- Prior art keywords
- mass spectrometer
- electrospray ionization
- wave voltage
- square
- sample ions
- 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.)
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- 238000000132 electrospray ionisation Methods 0.000 title claims description 46
- 150000002500 ions Chemical class 0.000 title claims description 42
- 239000007788 liquid Substances 0.000 title claims description 22
- 238000000034 method Methods 0.000 title claims description 21
- 230000004888 barrier function Effects 0.000 title claims description 7
- 238000004949 mass spectrometry Methods 0.000 title claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 239000003989 dielectric material Substances 0.000 claims description 4
- 238000010586 diagram Methods 0.000 description 23
- 230000036962 time dependent Effects 0.000 description 14
- 230000005684 electric field Effects 0.000 description 11
- 239000012491 analyte Substances 0.000 description 6
- 238000006062 fragmentation reaction Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
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- 239000007921 spray Substances 0.000 description 3
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- 238000006073 displacement reaction Methods 0.000 description 2
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- 230000000630 rising effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000001360 synchronised effect Effects 0.000 description 2
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- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
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- 238000001704 evaporation Methods 0.000 description 1
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- 238000004880 explosion Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
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- 238000005040 ion trap Methods 0.000 description 1
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- 238000001228 spectrum Methods 0.000 description 1
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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
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/0027—Methods for using particle spectrometers
- H01J49/0031—Step by step routines describing the use of the apparatus
-
- 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
- the invention relates to a method for the dielectrically impeded electrospray ionization of liquid samples and for the subsequent mass spectrometric analysis of the sample ions produced, in which the respective liquid sample is passed into a capillary-shaped feed channel, the surrounding wall of which is made of a dielectric material and is spaced on the outside from the free end has an electrode, an inlet of a mass spectrometer forming a counter electrode being arranged at a distance from the free end of the feed channel, forming an ion formation free space, through which the ions formed enter an openable and closable trap of the mass spectrometer, between the electrode and the inlet to generate the sample ions, a square wave voltage is applied and the trap of the mass spectrometer is alternately opened and closed, and the sample ions passing through the trap of the mass spectrometer in the mass spectrometer to be analyzed.
- electrospray describes the dispersion of a liquid in a large number of small charged droplets with the help of an electric field.
- the ions are transferred into the gas phase at atmospheric pressure, whereby this process is divided into four steps: In a first step, small charged electrolyte droplets are formed. In a second step, there is a continuous loss of solvent of these droplets by evaporation, the charge density on the droplet surface increasing. In a third step there is a repeated spontaneous disintegration of the droplets into micro droplets (Coulomb explosions). Finally, in a fourth step, the analyte molecules are desolvated upon transfer to the mass spectrometer.
- the electrospray ionization process begins with a continuous supply of the dissolved analyte to the tip of a capillary-shaped supply channel.
- electrical contact is made via the direct connection of an electrical conductor to the analyte solution.
- the applied electrical field between the free end of the capillary feed channel and the inlet of the mass spectrometer also penetrates the analyte solution.
- the positive ions are drawn to the surface of the liquid. Accordingly, the negative ions are pushed in the opposite direction until the electric field within the liquid is canceled by the redistribution of negative and positive ions or these ions are neutralized by electron exchange. This suppresses possible forms other than soft ionization, such as ionization by removing an electron from the analyte molecule, which would require very high electric fields.
- the positive ions accumulated on the liquid surface are drawn further towards the cathode.
- the surface of the droplets is enriched with positive charges that no longer have negative counterions, so that a positive net charge results.
- the electrophoretic separation of the ions is responsible for the charges in the droplets.
- the positive ions (as well as the negative ions after polarity reversal of the field) that are observed in the spectrum are always the ions that are already present in the (electrolyte) solution. Additional ions and also fragment ions of the analyte to be detected only become apparent when the voltage is very high observed when electrical discharges occur at the capillary tip (corona discharges).
- the electrode is brought into direct contact with the liquid or sample to be analyzed.
- the service life of this device is greatly limited, since the electrode inevitably corrodes so strongly after a certain period of use that it is no longer usable.
- the maximum voltage that can be applied is limited in these known devices, since otherwise undesirable corona discharges occur.
- a device and a method for the dielectric barrier electrospray ionization of liquid samples have become known.
- the respective liquid sample is passed into a capillary-shaped feed channel, the surrounding wall of which on the outside, spaced from the free end, has an electrode separated from the wall by a separating layer made of a dielectric material, one at a distance from the free end of the feed channel, forming an ion formation space , a counter electrode forming plate is arranged.
- Electrospray ionization is thus carried out by contactless application of a voltage, since the electrode of the feed channel has no direct contact with the sample liquid, by dielectric coupling of the electric field.
- the electric field is transmitted through a dielectric displacement of the charges through the channel walls without the functional mechanism being impaired. Since there is no direct contact between the electrodes and the sample liquid, corrosion of the Electrodes completely avoided, so that the life of the device is significantly increased. Furthermore, much higher voltages can be applied and higher currents can be induced with such a process control without a corona discharge igniting.
- Such an electrospray ionization enables mass spectrometric measurements, both in positive as well as in negative mode of the mass spectrometer, without having to change the polarity of the applied potential, and it reduces the risk of undesired discharges, which are induced by high electrical currents.
- a dielectric impeded electrospray ionization considerably higher ionization currents can be achieved than conventional electrospray ionization and thus reach measurement signals which, without the risk of fragmentation, are of the order of magnitude of 1 ⁇ A, whereas in the case of electrospray ionization which is not dielectrically impeded, a constant electrospray current of approximately 50 nA is achievable, fragmentation occurs at higher currents.
- the object of the invention is therefore to develop a method described above in such a way that only the positive or negative sample ions enter the mass spectrometer while maintaining the advantages of applying a square-wave voltage.
- the method according to the invention thus uses a square wave voltage for electrospray ionization which is not symmetrical, ie in which the clock ratio between alternating positive and negative potentials is not identical, but differs therefrom. Depending on the frequency of the voltages, this makes it possible to set the electrospray ionization in such a way that only positive or only negative sample ions enter the mass spectrometer.
- the high voltage used is in the order of 2 to 6 kV. It is provided that an asymmetrical square-wave voltage is applied between the electrode and the inlet, in which the clock ratio is selected such that only positive or negative sample ions are formed.
- the clock ratio of the square-wave voltage can preferably be set to 80:20, for example.
- the time and therefore the number of undesired (eg negative) sample ions formed is not sufficient to form a negative electrospray.
- only a positive electrospray is created and therefore a signal with only one polarity. This signal is about a factor 2 larger than in the generic method, which uses a symmetrical square wave voltage.
- FIG. 1 an electrospray ionization device 10 is shown in general form, which initially has a capillary-shaped feed channel 1, the tubular wall of which is denoted by 2 in this example.
- the feed channel 1 is arranged in such a way that its axis of symmetry 3 coincides with the axis of symmetry 3 'of an inlet 4 of a mass spectrometer (not shown further).
- the wall 2 is e.g. made of glass, i.e. from a dielectric material.
- a sample to be analyzed is introduced into the feed channel at the rear end 4 of the feed channel 1 and exits at the front free end 5.
- A, for example, tubular electrode 6 is arranged at a significant distance from the front free end 5 through the dielectric separating layer (wall 2) from the feed channel 1.
- This electrode 6 is connected to a high-voltage source, not shown, just like the inlet 4 of the mass spectrometer, which is designed as a counter electrode.
- a sample to be subsequently analyzed in the mass spectrometer is introduced into the feed channel 1 in liquid form, there is no contact between the liquid sample within the feed channel 1 and the electrode 6. If a high voltage is applied between the electrode 6 and the counter electrode formed by the inlet 4 and the liquid sample flows through the feed channel 1, the resulting electric field is transmitted through a dielectric displacement of the charges through the channel walls (dielectric wall 2). An electrospray 8 is generated without the electrode 6 coming into contact with the liquid. The ion spray generated hits the inlet 4 of the mass spectrometer, the ions then pass through the inlet 4 into an openable and closable trap of the mass spectrometer, not shown, and are analyzed in the mass spectrometer after they have passed the opened trap.
- the type of voltage applied to the electrodes is essential for the method according to the invention. Basically it is from “ Anal. Bioanal.Chem. (2010), pages 1767 to 1772 "known to use a normal, ie symmetrical square wave voltage. A voltage curve of a square wave voltage is in Fig. 2 shown. The resulting current profile can be seen to have alternating positive and negative current ranges, ie alternating positive and negative ions are generated.
- Fig. 3 shows an enlarged and quantitative representation of a positive current signal with dielectrically impeded electrospray ionization with square wave voltage compared to a current signal with non-dielectrically impeded conventional electrospray ionization.
- a constant electrospray current of preferably 50 nA is produced in a conventional electrospray ionization with a constant DC voltage.
- This current signal is in Fig. 3 hatched in descending order.
- undesirable fragmentations would occur at such high current intensities.
- an asymmetrical square-wave voltage is applied between the electrode 6 and the inlet 4 of the mass spectrometer, in which the clock ratio of the positive and negative polarities is different.
- asymmetrical square wave voltage is applied, in which the clock ratio of the square wave voltage is preferably 80:20.
- the clock ratio of the square wave voltage is preferably 80:20.
- Such a square-wave voltage curve is in the middle diagram Fig. 6 shown. This results in a current curve, which is shown in the diagram below Fig. 6 can be seen.
- This procedure is particularly suitable for high-frequency square-wave voltages with a frequency in the order of 200 Hz.
- an asymmetrical square-wave voltage with a frequency in the Hertz range is used, it is provided according to a second embodiment, not according to the invention, that an asymmetrical square-wave voltage is applied between the electrode 6 and the inlet 4 of the mass spectrometer, at which the frequency of the positive or negative polarities of the Opening frequency corresponds to the trap of the mass spectrometer.
- This procedure is the Fig. 7 refer to. It can be seen that the time-dependent course of the opening time of the mass spectrometer (upper diagram of the Fig. 7 ) the time-dependent course of the square-wave voltage signal (middle diagram of the Fig. 7 ) corresponds.
- the start of the positive electrospray is synchronized with the opening of the ion trap of the mass spectrometer, i.e. the dielectric electrospray is triggered on the frequency of the opening of the trap of the mass spectrometer.
- FIG. 8 shows a plurality in the embodiment Fig. 8 five electrospray ionization devices 10 arranged in a star or semicircular shape in relation to the inlet of the mass spectrometer indicated by 4 such that the ion spray S formed in each case hits the inlet 4.
- a square-wave voltage is applied between the electrode of the respective electrospray ionization device 10 and the inlet 4 of the mass spectrometer, the pulse ratio of the positive (or negative) polarities is adapted to the opening frequency of the trap of the mass spectrometer in such a way that the ion spray coming from the various electrospray ionization devices 10 is successive enters the trap of the mass spectrometer through the inlet.
- the corresponding voltage curve is in Fig. 9 shown.
- the top diagram of the Fig. 9 shows the time-dependent course of the opening time of the trap of the mass spectrometer.
- the square-wave voltage profiles of the five supply channels are shown with U 1 to U 5 .
- the square-wave voltage U 1 of the first electrospray ionization device 10 is triggered on the frequency of the trap opening of the mass spectrometer in such a way that the square-wave voltage signal is synchronized in time with the first opening interval of the trap and then in turn on the sixth, eleventh, etc.
- the voltage signal U 2 of the second electrospray ionization device 10 set so that the positive square wave voltage signal is in synchronism with the second opening interval of the trap and subsequently with the seventh, twelfth, etc. The same applies correspondingly to the subsequent voltage signals U 3 of the third electrospray ionization device 10, U 4 of the fourth electrospray ionization device 10 and U 5 of the fifth electrospray ionization device 10.
- electrosprays can be operated quasi-simultaneously, that is, depending on the opening of the trap of the mass spectrometer.
- the first rising edge is used to start the first electrospray ionization device 10
- the second for the second electrospray ionization device 10 and after the fifth again the first electrospray ionization device 10, analytes from different feed lines can be measured from different electrospray ionization devices 10 in succession with only one mass spectrometer.
- electrospray ionizers 10 of this type Fig. 8 can be integrated on a microchip, for example. All feed channels of the chip should be of the same length in order to avoid delaying the separated analytes on the one hand and hydrodynamic differences between the channels on the other. Such hydrodynamic differences could interfere with the separation.
- each electrospray ionization device 10 can be arranged in a star shape in a semicircle around the inlet 4 of the mass spectrometer.
- the radius of this arrangement should preferably correspond to the distance between the free end of a feed channel 1 and the inlet 4 of the mass spectrometer.
- each electrospray ionization device 10 is equipped with its own electrode, which is applied to the chip. With the help of high-voltage transistors, each electrode can be driven one after the other and a positive electrospray can be generated with a rising edge and a negative electrospray with every falling edge. It is switched so quickly that the hydrodynamic properties of the river are not disturbed. In this way, the analytes sprayed from the different feed channels can be measured by mass spectrometry and averaged over several cycles.
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- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Plasma & Fusion (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Electron Tubes For Measurement (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102011015517A DE102011015517B3 (de) | 2011-03-30 | 2011-03-30 | Verfahren zur dielektrisch behinderten Elektrosprayionisierung von flüssigen Proben und zur nachfolgenden massenspektrometrischen Analyse der erzeugten Probenionen |
PCT/EP2012/055279 WO2012130781A1 (de) | 2011-03-30 | 2012-03-26 | Verfahren zur dielektrisch behinderten elektosprayionisierung von flüssigen proben und zur nachfolgenden massenspektrometrischen analyse der erzeugten probenionen |
Publications (2)
Publication Number | Publication Date |
---|---|
EP2691974A1 EP2691974A1 (de) | 2014-02-05 |
EP2691974B1 true EP2691974B1 (de) | 2020-04-22 |
Family
ID=46017798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP12717215.3A Active EP2691974B1 (de) | 2011-03-30 | 2012-03-26 | Verfahren zur dielektrisch behinderten elektosprayionisierung von flüssigen proben und zur nachfolgenden massenspektrometrischen analyse der erzeugten probenionen |
Country Status (6)
Country | Link |
---|---|
US (1) | US20140001352A1 (ja) |
EP (1) | EP2691974B1 (ja) |
JP (1) | JP5814458B2 (ja) |
DE (1) | DE102011015517B3 (ja) |
ES (1) | ES2792462T3 (ja) |
WO (1) | WO2012130781A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6182572B2 (ja) * | 2015-07-09 | 2017-08-16 | 京セラ株式会社 | 携帯機器、制御方法及び制御プログラム |
CN107390102B (zh) * | 2017-09-04 | 2023-08-01 | 云南电网有限责任公司电力科学研究院 | 一种高场表面陷阱评估系统 |
JP7095579B2 (ja) * | 2018-12-05 | 2022-07-05 | 株式会社島津製作所 | 質量分析装置 |
EP3963622A4 (en) * | 2019-04-29 | 2023-05-31 | Ohio State Innovation Foundation | METHOD AND APPARATUS FOR MASS SPECTROMETRY |
CN111308000A (zh) * | 2020-03-24 | 2020-06-19 | 宁波大学 | 基于电喷雾的质谱分析系统 |
CN113325063B (zh) * | 2021-05-19 | 2024-05-03 | 宁波大学 | 胶体金免疫层析试纸检测结果的验证装置及方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5382793A (en) * | 1992-03-06 | 1995-01-17 | Hewlett-Packard Company | Laser desorption ionization mass monitor (LDIM) |
DE19947496C2 (de) | 1999-10-01 | 2003-05-22 | Agilent Technologies Inc | Mikrofluidischer Mikrochip |
US6967324B2 (en) * | 2000-02-17 | 2005-11-22 | Agilent Technologies, Inc. | Micro matrix ion generator for analyzers |
DE102005061381B4 (de) * | 2005-12-22 | 2017-10-05 | Leibniz - Institut Für Analytische Wissenschaften - Isas - E.V. | Vorrichtung zur Elektrosprayionisierung einer flüssigen Probe |
US8003937B2 (en) * | 2008-09-25 | 2011-08-23 | Ut-Battelle | Electrospray ion source with reduced analyte electrochemistry |
-
2011
- 2011-03-30 DE DE102011015517A patent/DE102011015517B3/de active Active
-
2012
- 2012-03-26 ES ES12717215T patent/ES2792462T3/es active Active
- 2012-03-26 EP EP12717215.3A patent/EP2691974B1/de active Active
- 2012-03-26 JP JP2014501558A patent/JP5814458B2/ja not_active Expired - Fee Related
- 2012-03-26 US US14/006,408 patent/US20140001352A1/en not_active Abandoned
- 2012-03-26 WO PCT/EP2012/055279 patent/WO2012130781A1/de active Application Filing
Non-Patent Citations (1)
Title |
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Also Published As
Publication number | Publication date |
---|---|
DE102011015517B3 (de) | 2012-06-28 |
US20140001352A1 (en) | 2014-01-02 |
EP2691974A1 (de) | 2014-02-05 |
JP2014512000A (ja) | 2014-05-19 |
WO2012130781A1 (de) | 2012-10-04 |
ES2792462T3 (es) | 2020-11-11 |
JP5814458B2 (ja) | 2015-11-17 |
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