Parallel mass analysis

Abstract

A system and method of mass spectrometry is provided. Ions from an ion source are stored in a first ion storage device and in a second ion storage device. Ions are ejected from the first ion storage device to a first mass analysis device during a first ejection time period, for analysis during a first analysis time period. Ions are ejected from the second ion storage device to a second mass analysis device during a second ejection time period. The ion storage devices are connected in series such that an ion transport aperture of the first ion storage device is in communication with an ion transport aperture of the second ion storage device. The first analysis time period and the second ejection time period at least partly overlap.

Claims

1. A mass spectrometer, comprising: an ion source, arranged to generate ions; an ion storage device, arranged to receive ions from the ion source and configured to sequentially release first and second samples of ions, the first and second samples of ions respectively having a first and a second range of mass-to-charge ratios, the first and second range of mass-to-charge ratios being different from one another; a first mass analyser, arranged to receive the first sample of ions from the ion storage device and to analyse the first sample of ions during a first time period; and a second mass analyser, arranged to receive the second sample of ions and to analyse the second sample of ions during a second time period; the first and second mass analysers each being selected from a group consisting of: an orbital trap mass analyser, a Fourier Transform-ion cyclotron resonance (FTICR) mass analyser, a multi-reflection time-of-flight mass analyser, and a multi-sector time of flight mass analyser; and wherein the first and second time periods at least partly overlap.

2. The mass spectrometer of claim 1, wherein the ion storage device is configured to mass-selectively eject ions of the first range of mass-to-charge ratios so as to provide the first sample of ions and ions of the second range of mass-to-charge ratios so as to provide the second sample of ions.

3. The mass spectrometer of claim 1, further comprising a mass selection device, located upstream from the ion storage device and configured selectively to transfer ions of the first range of mass-to-charge ratios and ions of the second range of mass-to-charge ratios to the ion storage device.

4. The mass spectrometer of claim 1, further comprising: a fragmentation device, arranged to receive ions generated by the ion source and to generate fragment ions; and wherein the second mass analyser is configured to receive the fragment ions as the second sample of ions.

5. The mass spectrometer of claim 1, wherein the first mass analyser is configured to analyse the first sample of ions so as to provide a preview scan, the mass spectrometer further comprising: a controller, configured to control the second mass analyser to terminate analysis of the second sample of ions on the basis of the preview scan.

6. The mass spectrometer of claim 1, wherein the ion storage device is a first ion storage device, the mass spectrometer further comprising: a second ion storage device, configured to store received ions; and wherein the first ion storage device is configured selectively to eject stored ions to the second ion storage device and wherein the second ion storage device is configured to eject stored ions to the second mass analyser so as to provide the second sample of ions.

7. The mass spectrometer of claim 6, wherein the second ion storage device is a curved trap.

8. The mass spectrometer of claim 1, wherein the first mass analyser and the second mass analyser are of different types.

9. The mass spectrometer of claim 1, wherein the first mass analyser and the second mass analyser are of the same type.

10. The mass spectrometer of claim 1, wherein the first and second mass analysers are integrated into a single construction.

11. The mass spectrometer of claim 1, further comprising a controller configured to adjust the operation of the second mass analyser based on results obtained from the first mass analyser.

12. The mass spectrometer of claim 1, wherein the ion storage device has first and second outlets, the first and second outlets being spaced apart from one another, and wherein the ion storage device releases the first sample of ions only through the first outlet and releases the second sample of ions only through the second outlet.

13. The mass spectrometer of claim 1, wherein the first and second mass analysers are operated at different resolutions.

14. The mass spectrometer of claim 1, wherein the signals produced by the first and second mass analysers are combined to generate a composite spectrum.

15. The mass spectrometer of claim 1, wherein the first and second mass analysers share at least one of an injector, a cooler, or an inlet.

16. A method of mass spectrometry, comprising: generating ions using an ion source; analysing ions generated using the ion source having a first range of mass-to-charge ratios in a first mass analyser during a first time period; analysing ions generated using the ion source having a second range of mass-to-charge ratios in a second mass analyser during a second time period; the first and second mass analysers each being selected from a group consisting of: an orbital trap mass analyser, a Fourier Transform-ion cyclotron resonance (FTICR) mass analyser, a multi-reflection time-of-flight mass analyser, and a multi-sector time of flight mass analyser; and wherein the first and second time periods at least partly overlap.

17. The method of claim 16, further comprising storing the ions generated by the ion source prior to analysis.

18. The method of claim 16, further comprising fragmenting ions generated by the ion source prior to analysis.

19. The method of claim 18, further comprising a step of mass selecting ions prior to fragmentation.

20. The method of claim 16, wherein the first and second mass analyser are of different types.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The invention may be put into practice in various ways, one of which will now be described by way of example only and with reference to the accompanying drawings in which:

(2) FIG. 1 shows a first embodiment of a mass spectrometer according to the present invention.

(3) FIG. 2 shows a part of the mass spectrometer of FIG. 1 with an improved pumping and trapping arrangement.

(4) FIG. 3 shows the part of the mass spectrometer shown in FIG. 2, with a further improved pumping and trapping arrangement.

SPECIFIC DESCRIPTION OF A PREFERRED EMBODIMENT

(5) Referring first to FIG. 1, a mass spectrometer according to the present invention is shown. The mass spectrometer comprises: an ion source 10; a preliminary ion storage device 15; a first ion storage device 20; a first mass analysis device 30; a second ion storage device 40; a second mass analysis device 50; a third ion storage device 60; and a third mass analysis device 70. Each of the mass analysis devices is an Orbitrap mass analyser, as described in U.S. Pat. No. 5,886,346. The preliminary ion storage device 15 is an ion trap.

(6) Ions are generated in the ion source 10 and are ejected from the source into preliminary ion storage 15 and from there into first ion storage device 20. The first ion storage device 20 is arranged to store ions to be analysed by the first mass analysis device 30 in a first storage time period. Ion storage device 20 maintains an appropriate pressure and temperature, such that the stored ions will be suitable for analysis by the first mass analysis device 30. The first ion storage device 20 then injects the stored ions into the first mass analysis device 30 during a first ejection time period.

(7) The second ion storage device 40 then stores ions for analysis by the second mass analysis device 50 during a second storage time period. These ions preferably flow through the first ion storage device 20 without being stored therein, although they may initially be stored by the first ion storage device 20. The first mass analysis device 30 performs some analysis of the injected ions during a first analysis time period.

(8) The second ion storage device 40 receives the ejected ions from the exit aperture of the first ion storage device 20. As described, it stores ions to be analysed by the second mass analysis device 50 and maintains an appropriate pressure and temperature, such that the stored ions will be suitable for analysis by the second mass analysis device 50. It then injects the stored ions into the second mass analysis device 50 during a second ejection time period. The second ejection time period at least partly overlaps with the first analysis time period. Hence, whilst the first mass analysis device 30 is performing an analysis, the second mass analysis device 50 is being filled with ions. This allows the mass spectrometer to be operated with increased efficiency. The second storage time period may also overlap with the first analysis time period.

(9) The third ion storage device 60 receives ions for the third mass analysis device 70. The second mass analysis device 50 performs some analysis of the injected ions during a second analysis time period.

(10) The third ion storage device 60 receives the transmitted ions from the exit aperture of the second ion storage device 40 and stores these ions. Again, these preferably flow through the first storage device 20 and second storage device 40 without being stored, although they may be stored by the first storage device 20 and/or second storage device 40 initially. It maintains an appropriate pressure and temperature, such that the stored ions will be suitable for analysis by the third mass analysis device 70. It then injects the stored ions into the third mass analysis device 70 during a third ejection time period. The third mass analysis device 70 performs some analysis of the injected ions during a third analysis time period.

(11) The configuration shown in FIG. 1 may be used in another, preferred mode. Ions are prepared in the ion trap 15, where they may also be detected, for example to determine the intensity of the incoming stream of ions from the source.

(12) In a most straightforward embodiment the ions are distributed to the different detectors one after the other in turn, as described above. The best number of detectors is in this case determined by the time and overhead for ion accumulation compared with the total detection time.

(13) In a more sophisticated implementation after a full mass scan, precursor ions determined from the preceding scan can be selected in the ion trap 15 and product ions can be formed in the ion trap 15 or a subsequent ion modification device, preferably downstream of the ion trap. These product ions are then detected in the next free mass analysis device.

(14) Either a pre-scan from the ion trap 15 can be used for data dependent information or a complete dataset from one of the detectors, or a preview dataset from one of the detectors.

(15) In an alternative mode of operation, the second storage device 40 may first be filled and the second mass analysis device 50 may first be operated. Whilst the second mass analysis device 50 is performing an analysis, the first ion storage device 20 may then be filled, such that the first storage time period and second mass analysis time period at least partly overlap. Alternatively, the third storage device 60 may initially be filled and the second storage time period and third mass analysis time period may at least partly overlap.

(16) A further improvement may be made by using a single ion storage device. The single ion storage device may be implemented in different ways. Referring to FIG. 2, a part of the mass spectrometer of FIG. 1 is shown. In FIG. 2, the mass spectrometer has a single ion storage device 100 and four mass analysis devices 110, 120, 130, 140.

(17) The ion storage device 100 is gas-filled and is capable of extracting ions in different directions. The ion storage device 100 is powered by a switchable RF power supply, for example a power supply similar to that described in WO-A-05124821.

(18) Advantageously, by using a single ion storage device with multiple mass analysers, a significant cost saving is gained, when compared with the embodiment shown in FIG. 1. Ion storage device 100 maintains an appropriate pressure and temperature, such that the stored ions will be suitable for analysis by each of mass analysis devices 110, 120, 130 and 140. The ion storage device 100 injects ions into each mass analysis device, one at a time. Once sufficient ions have been injected into a mass analysis device, for example mass analysis device 110, this mass analysis device begins to analyse the injected ions. Continuing this example, whilst mass analysis device 110 is performing an analysis, ion storage device 100 injects ions into mass analysis device 120. This procedure is continued for each mass analysis device.

(19) Acquisition of a high-resolution spectrum in each mass analysis device typically requires 200-1000 ms, while ion capture in the ion storage device could occur typically in 5-10 ms (although 100 ms for low-intensity ion beams is possible). Also, ion injection into each mass analysis device takes less than or equal to 1 ms. Therefore, there is sufficient time for ion storage device 100 to inject ions into one mass analysis device whilst at least one other mass analysis device is performing an analysis on previously injected ions. This procedure significantly increases the efficiency of the mass spectrometer.

(20) However, injecting ions from a single ion storage device into multiple mass analysis devices using this arrangement may increase the gas carryover. Hence, in order to ensure that the gas carryover is minimised, the pumping requirements for the mass analysis devices must be increased. Moreover, each mass analysis device requires its own ion optics arrangement for focusing the ion beam on its entrance.

(21) Referring to FIG. 3, a modified version of the part of the mass spectrometer shown in FIG. 2 is shown which addresses these issues. The mass spectrometer comprises ion storage device 200, ion optics 210 and mass analysis devices 110, 120, 130 and 140.

(22) Ion storage device 100 shown in FIG. 2 comprises a plurality of slots, one for each mass analysis device. In contrast, ion storage device 200 comprises only a single slot 205. Ions are ejected in a beam from ion storage device 200 through slot 205. Ion optics 210 are provided for deflecting the ejected ions into a UHV part of the mass spectrometer 220.

(23) The UHV part of the mass spectrometer comprises four mass analysis devices 110, 120, 130 and 140. Ion optics 210 directs the ion beam ejected from ion storage device 200 to one mass analysis device at a time. Additionally, the parameters of the ion optics 210 can be changed to allow a change of ion beam focus, such that the ion beam may be focused onto each mass analysis device. Such change of focal length could be achieved if ion optics 210 and/or ion storage device 200 follow non-concentric arcs.

(24) Further efficiency gains, through the use of an ion storage device together with multiple, parallel mass analysis devices are possible. Depending on the type of analyzer and construction the analysers may share power supplies, heating or cooling, pumping and so on. For example the Orbitrap mass analysis devices in the mass spectrometer may be powered by the same ultra-stable central electrode power supply. This results in a more compact arrangement. Nevertheless, ramping/pulsing and pre-amplification electronics should be individual for each Orbitrap. Even if pulsing of the central electrode on one Orbitrap results in voltage sagging on other Orbitraps during the detection, the duration of this perturbation is only <1-2 ms which is negligible comparing with the total duration of analysis. In this case, peak broadening would occur only at a level close to the baseline and so would not affect the appearance of mass spectra. Moreover, the mass analysis devices may share one or more of a common inlet, common cooler and common injector.

(25) The detection system for each mass analysis device may also benefit from economy of scale, for example by using parallel processing. Alternatively, frequency mixing could be employed, for example by shifting the mass spectrum from one Orbitrap into the range 1 to 2 Mhz, from a second Orbitrap into the range 2 to 3 MHz, a third Orbitrap into the range 3 to 4 MHz, and so on. The combined signal from the plurality of mass analysis devices may then be digitised by a single high-speed analogue to digital converter (e.g. 16-bit, 20 MHz).

(26) Whilst specific embodiments have been described herein, the skilled person may contemplate various modifications and substitutions. For example, the skilled person will understand that any other pulsed mass analysis device may be used instead of Orbitraps, for example FT ICR, RF ion traps, multi-reflection or multi-sector time-of-flight analysers and other types of electrostatic traps. Moreover, the plurality of mass analysis devices may comprise more than one different type of mass analysis device. This arrangement may allow the advantages of different mass analysis devices to be combined, when these mass analysis devices are used in parallel.

(27) The skilled person will also appreciate that irrespective of the type of mass analysis device used, when an ion storage device is used as described herein, components may be shared between the plurality of mass analysis devices. For example, electronic, mechanical, vacuum infrastructure may be shared. In many cases, multiple mass analysis devices may be integrated into one construction. Then, ions may be ejected from the ion storage devices into different parts of this integrated construction. For example, in the case of FT ICR this could be a multiple-segment ICR cell with several independent cells along the same axis inside the magnetic field. For multi-reflection systems, this could be injection of ions onto trajectories propagating at different angles so that they finish on different detectors.

(28) The skilled person will appreciate that any combination of the above embodiments may also be possible. For example, a mass spectrometer may comprise two consecutive ion storage devices, each pulsing ions into two opposite directions, each direction having a deflector to switch the beam between two mass analysis devices. Such arrangement would potentially allow parallel operation of 8 mass analysis devices. Although the gas leak from the ion storage device section of the instrument increases four-fold, the better pumping conductivity of all the elements of the associated ion optics would only require approximately doubling the pumping requirement. Additionally, both ion storage devices may be powered by the same RF supply.

(29) Additionally the skilled person may recognise the advantages in the plurality of mass analysis devices being of different types. For example, the different types may include orbital traps, multi-reflection traps, time of flight detectors, FT/MS detectors, ion traps and similar.

(30) Alternative ways to schedule the operation of a plurality of mass analysis devices according to the present invention may include the following. The mass analysis devices may be operated in sequence, according to a round robin approach, to produce a full mass spectrum. The mass analysis devices may instead be operated in sequence, but with automatic gain control, to produce a full mass spectrum.

(31) In a possible alternative embodiment, different mass analysis devices can be allocated different roles. One example of this is where the types of mass analysers are chosen according to the mass range and mass resolution they can achieve. In an MS-MS experiment for example, the first stage of mass selection for a particular experiment might only be possible using a mass analyser that can operate to select ions of a particularly high mass. However the daughter ions of interest for the second stage of mass analysis will be lower in mass and might be much lower in mass, but might require a higher mass resolution to separate them from neighbouring mass peaks for correct identification. Having one mass analyser that is capable of high mass ion selection and a second capable of high mass resolution at lower mass ranges is an example of a use for the present invention where different mass analysers are allocated different roles.

(32) In addition or alternatively, flexible analysis time periods can be scheduled, in accordance with the present invention. For example, the mass analysis devices can be operated sequentially, according to a round robin approach. Automatic gain control can also be implemented, such that initial measurements can be used to control measurements taken at a later time in either the same or a different mass analyser. Alternatively, as soon as a mass analysis device is inactive, it can be provided ions for a further mass analysis. Hence, the operation of mass analysis devices need not be scheduled in a strict order. This allows freedom of scheduling, but requires a more sophisticated system controller.

(33) The sequence of operation for the mass analysis devices can be optimised by use of preview scans from the detectors. If data from a detector in preview scan shows that the ion packets are not useful, the scan can be discarded and the detector can be made available earlier for a further ion packet to perform further analysis.

(34) This flexible scheduling can be combined with allocated roles for different mass analysers. For instance, a mass spectrometry system with four mass analysers can be considered. Full mass spectrometry can be carried out in analyser 1 and 3, data dependent MS based on preview information in traps 2 and 4 and AGC prescans in an ion trap. Alternatively, full mass spectrometry can be carried out in traps 1 and 3, data dependent mass spectrometry based on preview information in traps 2 and 4 and MS.sup.3 in an ion trap. Alternatively, full mass spectrometry can be carried out in trap 1, MS.sup.2 in trap 2 and MS.sup.3 in traps 3 and 4.

(35) Also possible are: fixed but different roles, for example certain traps being operated at higher resolution.