Dual Mode Ionization Device

Abstract

An ion source is disclosed that alternates between ionizing analytes in a sample by electrospray ionization and impact ionization.

Claims

1. An ion source for ionizing analyte in a sample comprising: a sprayer for spraying a liquid sample into a spray region; a voltage supply for supplying an electrical potential difference in the spray region, in a first ionization mode, so as to produce analyte ions by electrospray ionization; an impact surface onto which the sprayer sprays the sample, in a second ionization mode, so as to ionize the analyte by impact ionization; and a switching mechanism configured to alternate the ion source between the first and second ionization modes during a single experimental run.

2. The ion source of claim 1, wherein the voltage supply is arranged and configured to maintain said potential difference between the sprayer and a first downstream electrode in the first ionization mode such that analyte in the sample sprayed from the sprayer is ionized by electrospray ionization; and wherein said ion source is arranged and configured to spray said sample from said sprayer onto the first electrode in said second ionization mode so that the sample is ionized by impact ionization.

3. The ion source of claim 2, wherein the sprayer comprises a bore through which the liquid sample is sprayed, in use; and wherein the voltage supply is arranged and configured to maintain the bore at ground electrical potential, or a first reference electrical potential, during said first and second ionization modes; and to maintain the first electrode at a voltage of a first polarity relative to the ground or reference potential during said first ionization mode.

4. The ion source of claim 3, wherein the voltage supply is arranged and configured to maintain the first electrode at a voltage of a second polarity, opposite to the first polarity, relative to the ground or reference potential during said second ionization mode.

5. The ion source of claim 1, comprising a sample separator upstream of the sprayer and in fluid communication with the sprayer for separating components within the sample such that the sprayer receives and sprays different components of the sample at different times, optionally wherein the sample separator is a liquid chromatography separator.

6. The ion source of claim 1, comprising a translator mechanism arranged and configured to translate the sprayer between a first spraying angle or location in the first mode of operation and a second, different spraying angle or location in the second mode of operation.

7. The ion source of claim 1, comprising a spray guide arranged and configured to direct the spray from the sprayer to pass along a first pathway in the first ionization mode, and to direct the spray from the sprayer to pass along a second, different pathway in the second ionization mode; optionally wherein the spray guide deflects the spray so as to pass along the first pathway in the first ionization mode and/or deflects the spray so as to pass along the second pathway in the second ionization mode.

8. The ion source of claim 1, wherein sprayer comprises: an inner bore through which the liquid sample is sprayed, in the first and/or second ionization modes; a desolvation gas capillary surrounding the inner bore through which a desolvation gas is passed, in the first and/or second ionization modes, for desolvating the sample sprayed by the sprayer; and an electrical heater which, in the first and/or second ionization modes, heats the desolvation gas; wherein the voltage supply is arranged and configured to maintain the bore at ground electrical potential during said first and/or second ionization modes.

9. A mass and/or ion mobility spectrometer comprising: an ion source as claimed in claim 1; and a mass and/or ion mobility analyzer for mass and/or ion mobility analyzing ions produced by the first and second ionization modes.

10. The spectrometer of claim 9, wherein the spectrometer comprises a vacuum region and the impact surface and/or first electrode is arranged as an interface between the spray region and vacuum region; wherein the spectrometer is arranged and configured to maintain, in use, the spray region at a first pressure and the vacuum region at a second pressure lower than the first pressure; optionally wherein said first pressure is substantially atmospheric pressure.

11. The spectrometer of claim 10, wherein the impact surface and/or first electrode comprises an aperture and the spectrometer is arranged and configured, in use, to urge ions generated in the first and/or second ionization modes through the aperture into the vacuum region.

12. A method of ionizing a sample comprising; performing a first ionization mode in which the sample is electrosprayed so as to produce ions by electrospray ionization; performing a second ionization mode in which the sample is ionized by impact ionization; and alternating between the first and second ionization modes during a single experimental run.

13. The method of claim 12, wherein said first ionization mode comprises spraying said sample using a sprayer and maintaining an electrical potential difference between the sprayer and a first downstream electrode such that the sample sprayed from the sprayer is ionized by electrospray ionization; and wherein said second ionization mode comprises spraying said sample using said sprayer onto the first electrode so that the sample is ionized by impact ionization.

14. The method of claim 13, comprising spraying the sample through a bore in the sprayer and maintaining the bore at ground electrical potential, or a first reference electrical potential, during said first and second ionization modes; and comprising maintaining the first electrode at a voltage of a first polarity relative to the ground or reference potential during said first ionization mode.

15. The method of claim 14, comprising maintaining the first electrode at a voltage of a second, opposite polarity relative to the ground or reference potential during said second ionization mode.

16. The method of claim 12, comprising spatially separating different components within the sample upstream of the sprayer, and supplying the separated components to the sprayer such that the sprayer sprays different components of the sample at different times; optionally wherein the components are separated by a liquid chromatography separator.

17. The method of claim 16, wherein the method is alternated between the first and second ionization modes at a rate such that at least one of the components in the sample, or each component in the sample, is ionized in both the first and second ionization modes as it elutes from the separator and sprayer.

18. The method of claim 12, comprising alternating the sprayer between a first spraying angle or location in the first mode of operation and a second, different spraying angle or location in the second mode of operation.

19. The method of claim 12, comprising arranging the spray from the sprayer to pass along a first pathway in the first ionization mode, and the spray from the sprayer to pass along a second, different pathway in the second ionization mode; optionally by deflecting the spray so as to pass along the first pathway in the first ionization mode and/or deflecting the spray so as to pass along the second pathway in the second ionization mode.

20. A method of mass and/or ion mobility spectrometry comprising: ionizing a sample according to the method of claim 12; and mass and/or ion mobility analyzing ions produced in the first and second ionization modes in a mass and/or ion mobility spectrometer.

21. The method of claim 20, wherein a sprayer sprays the sample into a spray region in the first and second ionization modes, wherein the spectrometer comprises a vacuum region, wherein the method comprises maintaining the spray region at a first pressure and the vacuum region at a second pressure lower than the first pressure, and wherein the impact surface and/or first electrode is arranged as an interface between the spray region and vacuum region; optionally wherein said first pressure is substantially atmospheric pressure.

22. The method of claim 21, wherein the impact surface and/or first electrode comprises an aperture and the ions generated in the first and/or second ionization modes are urged through the aperture into the vacuum region.

23. An ion source for ionizing analyte in a sample comprising: a sprayer for spraying a liquid sample into a spray region; a voltage supply for supplying an electrical potential difference in the spray region, in a first ionization mode, so as to produce analyte ions by electrospray ionization; an impact surface onto which the sprayer sprays the sample, in a second ionization mode, so as to ionize the analyte by impact ionization; and further comprising one or more of: (i) a translator mechanism arranged and configured to translate the sprayer between a first spraying angle or location in the first mode of operation and a second, different spraying angle or location in the second mode of operation; and/or (ii) a spray guide arranged and configured to direct the spray from the sprayer to pass along a first pathway in the first ionization mode, and to direct the spray from the sprayer to pass along a second, different pathway in the second ionization mode.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0108] Various embodiments will now be described, by way of example only, and with reference to the accompanying drawings in which:

[0109] FIG. 1 shows a schematic of an embodiment according to the present invention;

[0110] FIG. 2A show an ion spectrum obtained according to an embodiment in an impact spray mode; and FIG. 2B show an ion spectrum obtained according to an embodiment in an electrospray mode.

DETAILED DESCRIPTION

[0111] FIG. 1 illustrates an embodiment of the invention. The instrument comprises a source of a sample to be analyzed 2, a liquid chromatography separator 3, a nebulizer 4 such as a pneumatically assisted nebulizer, a mass spectrometer 6 and an interface 8 for interfacing the nebulizer 4 with the mass spectrometer 6. As shown in FIG. 1, the nebulizer 4 may be grounded at a reference potential. A translator mechanism may be provided for translating the nebulizer between different spraying locations or spraying angles. A spray guide 7 may be provided for altering the pathway along which spray 32 from the nebulizer 4 travels.

[0112] The interface 8 comprises an interface cone 10 that is connected to a power supply 12 for supplying a voltage to the interface cone 10. The interface 8 also comprises an ion guide 14 for guiding ions from the interface cone 10 into the spectrometer 6.

[0113] The spectrometer 6 comprises a first vacuum chamber 16 that is maintained at a first pressure by vacuum pump 18. For example, the vacuum pump 18 may be operated to maintain the first vacuum chamber 16 at a pressure below 50 Torr, e.g., in the range of 1-10 Torr or 1-3 Torr. The spectrometer 6 comprises a second vacuum chamber 20 that is connected to the first vacuum chamber 16 by an orifice, e.g., such as a skimmer cone 22. The second vacuum chamber 20 is maintained at a second pressure by vacuum pump 24 that is lower than the first pressure in the first vacuum chamber 16. For example, the vacuum pump 24 may be operated to maintain the second vacuum chamber 20 at a pressure of 10.sup.−2 to 10.sup.−3 Torr.

[0114] The spectrometer 6 comprises a third vacuum chamber 26 that is connected to the second vacuum chamber 20 by an orifice 28. The third vacuum chamber 26 is maintained at a third pressure by vacuum pump 30 that is lower than the second pressure in the second vacuum chamber 20. For example, the vacuum pump 30 may be operated to maintain the third vacuum chamber 26 at a pressure of ≦10.sup.−5 Torr. An ion guide 32 may be provided in the second vacuum chamber 20 for guiding ions from the first vacuum chamber 16, through the second vacuum chamber 20, and into the third vacuum chamber 26. An analyzer 34, such as a mass and/or ion mobility is provided in the third vacuum chamber 26 for analyzing the ions. The analyzer 34 may be a Time of Flight mass analyzer, a quadrupole mass analyzer, an ion trap mass analyzer, or another type of mass analyzer.

[0115] In operation, sample is supplied from source 2 to liquid chromatography separator 3, which separates the components/compounds in the sample and then supplies the separated components/compounds to a bore in the nebulizer 4, which may be grounded. A gas flow may be arranged to flow passed the tip of the nebulizer 4 so as to nebulize the sample to form droplets 32, i.e. the nebulizer 4 may be a pneumatically-assisted nebulizer 4.

[0116] The instrument may be operated in at least two different modes. In a first mode, the nebulizer 4 is held at electrical ground and power supply 12 applies a negative voltage to interface cone 10. For example, in the range of −2 kV to −5 kV. The stress imposed by the electric field produced by the difference in electrical potential between the output of nebulizer 4 and interface cone 10 may cause the liquid flowing out of nebulizer 4 to break into an electrospray of (highly) positively charged droplets, clusters and ions. The electric field between nebulizer 4 and interface cone 10 therefore converts the liquid sample entering nebulizer 4 into a positively charged spray 32, including positively charged analyte ions from analyte molecules in the liquid stream.

[0117] The first vacuum chamber 16 may be maintained at a pressure lower than the pressure of the region in which the spray 32 is emitted by the nebulizer 4. As such, a gas flows from the region in which the spray 32 is emitted by the nebulizer into the orifice in the interface cone 10 and then into the first vacuum chamber 16. This flow of gas carries the electrosprayed droplets, clusters and ions such that at least some of the droplets, clusters and ions pass through the orifice in interface cone 10 and into first vacuum chamber 16.

[0118] After the ions enter the first vacuum chamber 16 they are directed by electric fields and gas flow within the spectrometer 6 to pass through the skimmer 22 into the second vacuum chamber 20. The ion guide 32 in the second vacuum chamber then guides the ions into the third vacuum chamber 26 such that the ions enter the analyzer 34 and are mass and/or ion mobility analyzed.

[0119] In a second mode of operation, the nebulizer 4 is held at electrical ground and power supply 12 applies a positive voltage to interface cone 10. Analyte molecules in the portion of the spray 32 that directly impacts the interface cone 10 are converted into positive ions by impact ionization. As described in relation to the first mode of operation, the gas flow into the interface cone 10 conveys the ions into the first vacuum chamber 16 and ultimately the ions are guided to the analyzer 35 for analysis.

[0120] The power supply is configured to repeatedly alternate the voltage applied to the interface cone 10 between the positive and negative values such that the instrument repeatedly alternates between the first and second modes during a single experimental run. The instrument is therefore able to ionize analyte molecules by both electrospray and impact spray during a single experimental run. For example, the sample may be separated by chromatography prior to being nebulized in the nebulizer 4, and the voltage applied to the interface cone 10 may be repeatedly alternated between the positive and negative values at a rate such that ions in each chromatographic peak are subjected to both electrospray and impact ionization. For example, the voltage applied to the interface cone 10 may be repeatedly alternated between the positive and negative values at a rate in the range of 100 Hz to 1 KHz.

[0121] The optimal position of the nebulizer 4 relative to the interface cone 10 for electrospray ionization may be different to optimal position of the nebulizer 4 relative to the interface cone 10 for impact ionisation. The instrument may therefore include a translator mechanism 5 that moves the nebulizer 4 to a first position when the instrument is operated in the first mode and a second position when the instrument is operated in the second mode. The nebulizer 4 may therefore repeatedly oscillate between first and second positions in synchronism with the instrument repeatedly alternating between operating in the first and second modes. For example, the nebulizer 4 may oscillate back and forth along an arc between the first and second positions.

[0122] Alternately, rather than moving the nebulizer 4 itself between different positions in the first and second modes of operation, the path of the spray 32 may be diverted in one or both of the first and second modes such that the path of the spray 32 is different in the first and second modes. This may be achieved by using a spray guide 7 to guide the droplets along different pathways in the different modes. For example, the spray guide 7 may comprise a tube moves between different positions in the two modes for guiding the spray along different pathways in the different modes. Alternatively, the spray guide 7 may be a gas curtain or gas flow that is directed in different directions or has different flow rates in the two modes, for guiding the spray along different pathways in the different modes.

[0123] FIG. 2A and FIG. 2B show total ion currents measured as a function of time for the analysis of sulfadimethoxine in the impact spray mode and the grounded electrospray mode, respectively. In both modes, the sample of sulfadimethoxine was nebulized in the nebulizer 4 using a nebulizing gas of pure nitrogen. During the impact spray mode the interface cone 10 was maintained at +1280 V and generated positive ions from the sulfadimethoxine impacting on the interface cone 10. During the electrospray mode the electrospray mode the interface cone 10 was maintained at a negative voltage and generated positive electrospray ions from the sulfadimethoxine. It can be seen by comparing FIGS. 2A and 2B that both ionization modes produce analyte ions for analysis, but that the analyte is ionized more effectively by electrospray ionisation since the total ion current is higher in FIG. 2B. In contrast, other analytes in a sample may be more effectively ionized by the impact spray mode. As such, alternating between the two modes enables a greater range of analytes to be ionised effectively in a single experimental run.

[0124] Although the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.

[0125] For example, in FIG. 1 the axis through the exit orifice of the nebulizer 4 is oriented orthogonally to the axis through the orifice in the interface cone 10. However, it is contemplated that the axis through the exit orifice of the nebulizer 4 may be oriented at other angles with respect to the axis through the orifice in the interface cone 10.