Targeted Analysis for Tandem Mass Spectrometry

• US 20140131567A1
• Filed: 06/19/2012
• Published: 05/15/2014
• Est. Priority Date: 06/23/2011
• Status: Active Grant

• Current Assignee: Thermo Fisher Scientific GmbH (Thermo Fisher Scientific Incorporated)
• Original Assignee: Thermo Fisher Scientific GmbH (Thermo Fisher Scientific Incorporated)
• Inventors: Makarov, Alexander
• Granted Patent: US 8,957,369 B2
• Time in Patent Office: Days
• US Class Current: 250/283
• CPC Class Codes: H01J 49/0031 Step by step routines describing the use of the apparatus H01J49/0081 takes precedence
• CPC Class Codes: H01J 49/004 Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
• CPC Class Codes: H01J 49/0063 by applying a resonant excitation voltage
• CPC Class Codes: H01J 49/0081 Tandem in time, i.e. using a single spectrometer
• CPC Class Codes: H01J 49/0422 for gaseous samples interfaces to gas chromatographs G01N30/7206
• CPC Class Codes: H01J 49/061 Ion deflecting means, e.g. ion gates
• CPC Class Codes: H01J 49/40 Time-of-flight spectrometers H01J49/36 takes precedence

Abstract

A tandem mass spectrometer and method are described. Precursor ions are generated in an ion source (10) and an ion injector (21, 23) injects ions towards a downstream ion guide (50, 60) via a single or multi reflection TOF device (30) that separates ions into packets in accordance with their m/z. A single pass ion gate (40) in the path of the precursor ions between the ion injector (21, 23) and the ion guide (50, 60) is controlled so that only a subset of precursor ion packets, containing precursor ions of interest, is allowed onward transmission to the ion guide (50, 60). A high resolution mass spectrometer (70) is provided for analysis of those ions, or their fragments, which have been allowed passage through the ion gate (40). The technique permits multiple m/z ranges to be selected from a wise mass range of precursors, with optional fragmentation of one or more of the chosen ion species.

Claims

1. A method of tandem mass spectrometry, comprising the steps of:

a) generating precursor ions in an ion source;

b) guiding the precursor ions into an ion injector;

c) ejecting the precursor ions from the ion injector towards an ion guide, via an ion gate, so that the precursor ions arrive at the said ion gate only once on their passage to the ion guide, the precursor ions arriving as a temporally separated plurality of ion packets each containing ions of a respective one of a plurality of different ion species;

d) controlling the ion gate so as to sequentially select from the plurality of ion packets arriving at the ion gate, a subset of a plurality of ion packets deriving from a subset of precursor ion species of interest;

e) mixing the selected subset of a plurality of ion packets in the ion guide; and

f) analyzing the resulting ion population derived from the mixed selected subset of ion packets in a high resolution mass analyzer.

2. The method of claim 1, further comprising, after selecting the subset of ion packets by controlling the ion gate, fragmenting at least some of the selected precursor ions.

3. The method of claim 2, wherein the step of fragmenting at least some of the selected precursor ions comprises fragmenting at least some of the different ion species at different times, using different respective fragmentation energies.

4. The method of claim 2, wherein the step of fragmenting at least some of the selected precursor ions comprises fragmenting the ions of each of the different precursor ion species at different times, using different respective optimized energies of fragmentation.

5. The method of claim 2, wherein the step of fragmenting the ions comprises one or more of the techniques selected from the list comprising Electron Transfer Dissociation (ETD);

Infrared Multiphoton Dissociation (IRMPD);

Ozone Induced Dissociation (OzID);

Ultraviolet lamp and Ultraviolet Dissociation.

6. The method of claim 1 wherein the step c) further comprises ejecting the precursor ions into a time of flight mass spectrometer for temporally separating the precursor ions into ion packets prior to arrival at the ion gate.

7. The method of claim 6, wherein the step of ejecting the precursor ions into a time of flight mass spectrometer comprises one or more of ejecting the ions into a single reflection time of flight (TOF) mass analyser, a multi-reflection time of flight (TOF) mass analyser, a multi-sector reflection time of flight (TOF) mass analyser, and an orbital time of flight device.

8. The method of claim 1 wherein the ion guide comprises an ion accumulation means and the step e) comprises storing the selected subset of a plurality of ion packets in the ion accumulation means.

9. The method of claim 1, further comprising accumulating, in the ion guide, and over multiple cycles of the method steps a) to e), a desired number of ions for multiple precursor ion species of interest, the step f) further comprising analyzing in parallel the accumulated selected ions.

10. The method of claim 2, further comprising accumulating, in the ion guide, and over multiple cycles of the method steps (a) to (e), the fragments of a desired number of ions for multiple precursor ion species of interest, the step (f) further comprising analyzing, in parallel, the accumulated fragment ions.

11. The method of claim 10, wherein the step of accumulating over multiple cycles comprises, during the step d) of multiple cycles, controlling the ion gate so as to select ion packets containing different subsets of the plurality of precursor ion species, such that, over N cycles (N is an integer>

1), ions of a first ion species m₁/z₁ are selected for fragmentation in M of those cycles (M is an integer≦

N) whereas ions of a second ion species m₂/z₂ are selected for fragmentation in a different number P of cycles (P is an integer;

P≦

N but P≠

M).

12. The method of claim 11, further comprising selecting a number of cycles N of the method steps (a) to (e) for each m/z, in accordance with the intensity of each such m/z in the spectrum of ions generated by the ion source, such that more intense ions species are accumulated in fewer cycles than less intense ion species.

13. The method of claim 1, wherein the step d) comprises selecting a subset of ion packets deriving from a subset of between 10 and 100 precursor ion species ejected from the ion trap.

14. The method of claim 1, wherein the step d) of controlling the ion gate comprises allowing passage of the selected subset of ion packets through the ion gate and directly into the ion guide.

15. The method of claim 14, further comprising controlling the ion gate so as to divert those ion packets from the ion trap which are not to be further analyzed, so that they do not enter the ion guide.

16. The method of claim 1, further comprising carrying out a preliminary mass analysis of all precursor ions to identify precursor ion species of interest and their relative abundances.

17. The method of claim 1, wherein the step f) of analyzing the resulting ion population comprises ejecting the ions in the ion guide to one of a time of flight (TOF), orbital electrostatic trap or FT-ICR mass analyzer.

18. The method of claim 1, further comprising the steps of carrying out the steps (a) to (f) a plurality of times, in respect of a corresponding plurality of different subsets of ion packets;

and combining the results of the analyses of the plurality of different subsets of ion packets by the high resolution mass analyser so as to form a composite mass spectrum.

19. The method of claim 1, wherein the step (b) of guiding the precursor ions into an ion injector comprises trapping the precursor ions in an ion trap, the step (c) then comprising ejecting the ions from the ion trap towards the ion guide.

20. The method of claim 1, wherein the step (c) of ejecting the precursor ions from the ion injector comprises ejecting the ions orthogonally.

21. A tandem mass spectrometer comprising:

an ion source for generating precursor ions;

an ion injector arranged downstream of the ion source, for ejecting precursor ions received from the ion source towards a downstream ion guide;

a single pass ion gate, arranged in a path of precursor ions ejected from the ion injector towards the downstream ion guide, the precursor ions arriving at the ion gate as a plurality of temporally separated ion packets each containing ions of a respective one of a plurality of different ion species;

an ion gate controller configured to control the single pass ion gate so as to permit passage of only a subset of ion packets containing a respective subset of a plurality of precursor ion species of interest;

wherein the ion guide is configured to receive precursor ions that are permitted to pass through the single pass ion gate;

the tandem mass spectrometer further comprising;

a high resolution mass analyzer arranged to analyze the ions or their fragments.

22. The mass spectrometer of claim 21,

wherein the ion guide comprises or includes one or both of an ion storage device and a fragmentation cell.

23. The mass spectrometer of claim 22, wherein the ion guide comprises or includes a fragmentation cell, arranged to receive the subset of ion packets selected for passage by the single pass ion gate, and to carry out fragmentation of the subset.

24. The mass spectrometer of claim 21, further comprising one or more of a single reflection time of flight (TOF) mass analyser, a multi-reflection time of flight (TOF) mass analyser, a multi-sector reflection time of flight (TOF) mass analyser, and an orbital time of flight device, arranged between the ion injector and the ion gate, for separating ions after ejection from the ion injector on their way to the ion gate.

25. The mass spectrometer of claim 21, wherein the ion injector is an ion trap for trapping ions received from the ion source and ejecting them towards the downstream ion guide.

26. The mass spectrometer of claim 21, wherein the ion injector comprises first and second parallel plates, one of which forms an extraction plate.

27. The mass spectrometer of claim 26, wherein the extraction plate being formed of or including a grid or slit.

28. The mass spectrometer of claim 26, wherein the ion injector is arranged to eject ions in a director substantially orthogonal to the direction of input of precursor ions from the ion source.

29. The mass spectrometer of claim 21, wherein the ion injector is a non-trapping DC or RF only ion guide.