Mass spectrometer Number:6,762,404 from the United States Patent and Trademark Office (PTO) owispatent A mass spectrometer includes a fragmentation cell having a plurality of ring or plate-like electrodes with apertures through which ions are transmitted. An axial DC gradient is preferably maintained along at least a portion of the length of the fragmentation cell in order to improve the transit time of ions through the device.<H spectrometer, Mass, Mass, spectromet, 6762404.html, Patent, pto, 6762404

Title: Mass spectrometer

Abstract: A mass spectrometer includes a fragmentation cell having a plurality of ring or plate-like electrodes with apertures through which ions are transmitted. An axial DC gradient is preferably maintained along at least a portion of the length of the fragmentation cell in order to improve the transit time of ions through the device.

Patent Number: 6,762,404 Issued on 07/13/2004 to Bateman, et al.

Inventors: Bateman; Robert Harold (Knutsford, GB), Giles; Kevin (Altrincham, GB), Pringle; Steve (Darwen, GB)
Assignee: Micromass UK Limited (Manchester, GB)

Appl. No.: 10/178,347

Filed: June 25, 2002

Foreign Application Priority Data


Jun 25, 2001 [GB]			0115429
Aug 17, 2001 [GB]			0120096
Aug 17, 2001 [GB]			0120122
Mar 15, 2002 [GB]			0206164

Current U.S. Class: 250/281 ; 250/282; 250/287

Current International Class: H01J 49/16 (20060101); H01J 49/10 (20060101)

Field of Search: 250/281,287,282,292

References Cited [Referenced By]

U.S. Patent Documents


5206506	April 1993	Kirchner
5572035	November 1996	Franzen
5811800	September 1998	Franzen et al.
5818055	October 1998	Franzen
5847386	December 1998	Thomson et al.
5905258	May 1999	Clemmer et al.
6087658	July 2000	Kawato
6107628	August 2000	Smith et al.
6417511	July 2002	Russ, IV et al.
6489610	December 2002	Barofsky et al.
6545268	April 2003	Verentchikov et al.
6559444	May 2003	Franzen
2002/0063207	May 2002	Bateman et al.
2002/0063209	May 2002	Bateman et al.
2002/0063210	May 2002	Bateman et al.
2002/0079443	June 2002	Krutchinsky et al.
2002/0113207	August 2002	Lee et al.
2002/0148959	October 2002	Weiss et al.

Foreign Patent Documents


2281405	Mar., 2000	CA
1271138	Jan., 2003	EP
2315364	Jan., 1998	GB
2375653	Nov., 2002	GB
11-307040	Nov., 1999	JP
2000-113852	Apr., 2000	JP
2000-123780	Apr., 2000	JP
WO 97/49111	Dec., 1997	WO
WO 02/43105	May., 2002	WO

Other References

Fuhrer et al. "Mobility Spectrometer", pub. No.: US 2002/0032929 A1, Oct. 25, 2001.* .
Wang et al. "Apparatus and Methods for Analyzing Samples in a Dual Ion Trap Mass Spectrometer", publication No.: US 2002/0121594 A1, Sep. 5, 2002.* .
Franzen et al., "Electrical Ion Guides" ASMS Book of Abstracts, pp. 1170, 1996. .
Shaffer et al., "A Novel Ion Funnel for Ion Focusing at Elevated Pressures", ASMS Book of Abstracts, pp. 375, 1997. .
Gerlich, "Rf Ion Guides", Encyclopedia of Mass Spectrometry, vol. 5, Chemistry and Physics of Gas Phase Ions, pp. 1-34, 2003. .
Luca et al., "On the Combination of a Linear Field Free Trap With a Time-of-Flight Mass Spectrometer", Review of Scientific Instruments, vol. 72, No. 7, pp. 2900-2908, 2001. .
Shaffer et al., "A Novel Ion Funnel for Focusing Ions at Elevated Pressure Using Electrospray Ionization Mass Spectrometry", Rapid Communications in Mass Spectrometry, vol. 11, pp. 1813-1817, 1997. .
Teloy et al., "Integral Cross Sections For Ion-Molecule Reactions. I. The Guided Beam Technique", Chemical Physics, pp. 417-427, 1974. .
Guan et al., "Stacked-Ring Electrostatic Ion Guide", Journal American Society for Mass Spectometry, vol. 7, pp. 101-106, 1996. .
Gerlich et al., "Ion Trap Studies of Association Processes in Collisions of CH.sub.3 .sup.+ and CD.sub.3.sup.+ With n-H.sub.2, p-H.sub.2, D.sub.2, and He at 80 K", The Astrophysical Journal, vol. 347, pp. 849-854, 1989. .
Kim et al., "Design and Implementation of a New Electrodynamic Ion Funnel", Analytical Chemistry, vol. 72, No. 10, pp 2247-2255, 2000. .
Tolmachev et al., "Charge Capacity Limitations of Radio Frequency Ion Guides in Their Use for Improved Ion Accumulation and Trapping in Mass Spectrometry", Analytical Chemistry, vol. 72, No. 5, pp. 970-978, 2000. .
Shaffer et al., "Characterization of an Improved Electrodynamic Ion Funnel Interface for Electrospray Ionization Mass Spectrometry", Analytical Chemistry, vol. 71, No. 15, pp. 2957-2964, 1999. .
Shaffer et al., "An Ion Funnel Interface for Improved Ion Focusing and Sensitivity Using Electrospray Ionization Mass Spectrometry", Analytical Chemistry, vol. 70, No. 19, pp. 4111-4119, 1998. .
Giles et al., "Evaluation of a Stacked-Ring Radio Frequency Ion Transmission Device at Intermediate Pressures", ASMS, 2001. .
Gerlich, "Inhomogeneous RF Fields: A Versatile Tool for the Study of Processes with Slow Ions", Advances in Chemical Physics Series, vol. 82, pp. 1-176, 1992..

Primary Examiner: Wells; Nikita
Assistant Examiner: Hashmi; Zia R.
Attorney, Agent or Firm: Diederiks & Whielaw, PLC

Parent Case Text

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application Serial No. 60/364,597 filed Mar. 18, 2002.

Claims

What is claimed is:

1. A mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of said electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient is maintained in use along at least a portion of the length of said fragmentation cell.

2. A mass spectrometer as claimed in claim 1, wherein said fragmentation cell comprises a plurality of segments, each segment comprising a plurality of electrodes having apertures through which ions are transmitted and wherein all the electrodes in a segment are maintained at substantially the same DC potential and wherein adjacent electrodes in a segment are supplied with different phases of an AC or RF voltage.

3. A mass spectrometer as claimed in claim 1, wherein ions are arranged to be trapped within said fragmentation cell in a mode of operation.

4. A mass spectrometer as claimed in claim 1, wherein said fragmentation cell consists of: (i) 10-20 electrodes; (ii) 20-30 electrodes; (iii) 30-40 electrodes; (iv) 40-50 electrodes; (v) 50-60 electrodes; (vi) 60-70 electrodes; (vii) 70-80 electrodes; (viii) 80-90 electrodes; (ix) 90-100 electrodes; (x) 100-110 electrodes; (xi) 110-120 electrodes; (xii) 120-130 electrodes; (xiii) 130-140 electrodes; (xiv) 140-150 electrodes; and (xv) >150 electrodes.

5. A mass spectrometer as claimed in claim 1, wherein the diameter of the apertures of at least 50% of the electrodes forming said fragmentation cell is selected from the group consisting of: (i) .ltoreq.10 mm; (ii) .ltoreq.9 mm; (iii) .ltoreq.8 mm; (iv) .ltoreq.7 mm; (v) .ltoreq.6 mm; (vi) .ltoreq.5 mm; (vii) .ltoreq.4 mm; (viii) .ltoreq.3 mm; (ix) .ltoreq.2 mm; and (x) .ltoreq.1 mm.

6. A mass spectrometer as claimed in claim 1, wherein said fragmentation cell is maintained, in use, at a pressure selected from the group consisting of: (i) >1.0.times.10.sup.-3 mbar; (ii) >5.0.times.10.sup.-3 mbar; (iii) >1.0.times.10.sup.-2 mbar; (iv) 10.sup.-3 -10.sup.-2 mbar; and (v) 10.sup.-4 -10.sup.-1 mbar.

7. A mass spectrometer as claimed in claim 1, wherein at least 50%, 60%, 70%, 80%, 90% or 95% of the electrodes forming the fragmentation cell have apertures which are substantially the same size or area.

8. A mass spectrometer as claimed in claim 1, wherein the thickness of at least 50% of the electrodes forming said fragmentation cell is selected from the group consisting of: (i) .ltoreq.3 mm; (ii) .ltoreq.2.5 mm; (iii) .ltoreq.2.0 mm; (iv) .ltoreq.1.5 mm; (v) .ltoreq.1.0 mm; and (vi) .ltoreq.0.5 mm.

9. A mass spectrometer as claimed in claim 1, further comprising an ion source selected from the group consisting of: (i) Electrospray ("ESI") ion source; (ii) Atmospheric Pressure Chemical Ionisation ("APCI") ion source; (iii) Atmospheric Pressure Photo Ionisation ("APPI") ion source; (iv) Matrix Assisted Laser Desorption Ionisation ("MALDI") ion source; (v) Laser Desorption Ionisation ion source; (vi) Inductively Coupled Plasma ("ICP") ion source; (vii) Electron Impact ("EI) ion source; and (viii) Chemical Ionisation ion source.

10. A mass spectrometer as claimed in claim 1, wherein at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of said electrodes are connected to both a DC and an AC or RF voltage supply.

11. A mass spectrometer as claimed in claim 1, wherein said fragmentation cell comprising a housing having an upstream opening for allowing ions to enter said fragmentation cell and a downstream opening for allowing ions to exit said fragmentation cell.

12. A mass spectrometer as claimed in claim 1, wherein said fragmentation cell has a length selected from the group consisting of: (i) <5 cm; (ii) 5-10 cm; (iii) 10-15 cm; (iv) 15-20 cm; (v) 20-25 cm; (vi) 25-30 cm; and (vii) >30 cm.

13. Amass spectrometer as claimed in claim 1, wherein the axial DC voltage difference maintained along a portion of said fragmentation cell is selected from the group consisting of: (i) 0.1-0.5 V; (ii) 0.5-1.0 V; (iii) 1.0-1.5 V; (iv) 1.5-2.0 V; (v) 2.0-2.5 V; (vi) 2.5-3.0 V; (vii) 3.0-3.5 V; (viii) 3.5-4.0 V; (ix) 4.0-4.5 V; (x) 4.5-5.0 V; (xi) 5.0-5.5 V; (xii) 5.5-6.0 V; (xiii) 6.0-6.5 V; (xiv) 6.5-7.0 V; (xv) 7.0-7.5 V; (xvi) 7.5-8.0 V; (xvii) 8.0-8.5 V; (xviii) 8.5-9.0 V; (xix) 9.0-9.5 V; (xx) 9.5-10.0 V; and (xxi) >10V.

14. A mass spectrometer as claimed in claim 1, wherein an axial DC voltage gradient is maintained along at least a portion of said fragmentation cell selected from the group consisting of: (i) 0.01-0.05 V/cm; (ii) 0.05-0.10 V/cm; (iii) 0.10-0.15 V/cm; (iv) 0.15-0.20 V/cm; (v) 0.20-0.25 V/cm; (vi) 0.25-0.30 V/cm; (vii) 0.30-0.35 V/cm; (viii) 0.35-0.40 V/cm; (ix) 0.40-0.45 V/cm; (x) 0.45-0.50 V/cm; (xi) 0.50-0.60 V/cm; (xii) 0.60-0.70 V/cm; (xiii) 0.70-0.80 V/cm; (xiv) 0.80-0.90 V/cm; (xv) 0.90-1.0 V/cm; (xvi) 1.0-1.5 V/cm; (xvii) 1.5-2.0 V/cm; (xviii) 2.0-2.5 V/cm; (xix) 2.5-3.0 V/cm; and (xx) >3.0 V/cm.

15. A mass spectrometer comprising: an ion source; one or more ion guides; a first quadrupole mass filter; a fragmentation cell for fragmenting ions, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of said electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient is maintained in use along at least a portion of the length of said fragmentation cell; a second quadrupole mass filter; and a detector.

16. A mass spectrometer comprising: an ion source; one or more ion guides; a quadrupole mass filter; a fragmentation cell for fragmenting ions, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of said electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient is maintained in use along at least a portion of the length of said fragmentation cell; and a time of flight mass analyser.

17. A mass spectrometer as claimed in claim 16, wherein said fragmentation cell comprises a plurality of segments, each segment comprising a plurality of electrodes having apertures through which ions are transmitted and wherein all the electrodes in a segment are maintained at substantially the same DC potential and wherein adjacent electrodes are supplied with different phases of an AC or RF voltage.

18. A mass spectrometer as claimed in claim 16, wherein said one or more ion guides comprise one or more AC or RF only ion tunnel ion guides.

19. A mass spectrometer as claimed in claim 16, wherein said one or more ion guides comprise one or more hexapole ion guides.

20. A mass spectrometer comprising: a first mass filter/analyser; a fragmentation cell for fragmenting ions, said fragmentation cell being arranged downstream of said first mass filter/analyser and comprising at least 20 electrodes having apertures through which ions are transmitted in use, wherein at least 75% of said electrodes are connected to both a DC and an AC or RF voltage supply and wherein a non-zero axial DC voltage gradient is maintained in use along at least 75% of the length of said fragmentation cell; and a second mass filter/analyser arranged downstream of said fragmentation cell.

21. A mass spectrometer as claimed in claim 20, wherein said first mass filter/analyser comprises a quadruople mass filter/analyser and said second mass filter comprises a quadrupole mass filter/analyser or a time of flight mass analyser.

22. A mass spectrometer comprising: a fragmentation cell comprising .gtoreq.10 ring or plate electrodes having substantially similar internal apertures between 2-10 mm in diameter arranged in a housing having a collision gas inlet port, wherein a collision gas is introduced in use into said fragmentation cell at a pressure of 10.sup.-4 -10.sup.-1 mbar and wherein a DC potential gradient is maintained, in use, along the length of the fragmentation cell.

23. A mass spectrometer as claimed in claim 22, further comprising an ion source and ion optics upstream of said fragmentation cell, wherein said ion source and/or said ion optics are maintained at potentials such that at least some of the ions entering said fragmentation cell have, in use, an energy .gtoreq.10 eV for a singly charged ion such that they are caused to fragment.

24. A mass spectrometer comprising: an ion source; a fragmentation cell for fragmenting ions, said fragmentation cell comprising at least ten plate-like electrodes arranged substantially perpendicular to the longitudinal axis of said fragmentation cell, each said electrode having an aperture therein through which ions are transmitted in use, said fragmentation cell being supplied in use with a collision gas at a pressure .gtoreq.10.sup.-3 mbar, wherein adjacent electrodes are connected to different phases of an AC or RF voltage supply and a DC potential gradient .gtoreq.0.01 V/cm is maintained over at least 20% of the length of said fragmentation cell; and ion optics arranged between the ion source and the fragmentation cell; wherein in a mode of operation the ion source, ion optics and fragmentation cell are maintained at potentials such that singly charged ions are caused to have an energy .gtoreq.10 eV upon entering said fragmentation cell so that at least some of said ions fragment into daughter ions.

25. A mass spectrometer comprising: a fragmentation cell comprising at least three segments, each segment comprising at least four electrodes having substantially similar sized apertures through which ions are transmitted in use; wherein in a mode of operation: electrodes in a first segment are maintained at substantially the same first DC potential but adjacent electrodes are supplied with different phases of an AC or RE voltage supply; electrodes in a second segment are maintained at substantially the same second DC potential but adjacent electrodes are supplied with different phases of an AC or RF voltage supply; electrodes in a third segment are maintained at substantially the same third DC potential but adjacent electrodes are supplied with different phases of an AC or RF voltage supply; wherein said first, second and third DC potentials are all different.

26. A mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of said electrodes are connected to an AC or RF voltage supply.

27. A mass spectrometer as claimed in claim 26, wherein at least some of said electrodes are also connected to a DC voltage supply and wherein an axial DC voltage gradient is maintained in use along at least a portion of the length of said fragmentation cell.

28. A mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein in a mode of operation at least a portion of the fragmentation cell is maintained at a DC potential so as to prevent ions from exiting the fragmentation cell.

29. A mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein the transit time of ions through the fragmentation cell is selected from the group comprising: (i) .ltoreq.0.5 ms; (ii) .ltoreq.1.0 ms; (iii) .ltoreq.5 ms; (iv) .ltoreq.10 ms; (v) .ltoreq.20 ms; (vi) 0.01-0.5 ms; (vii) 0.5-1 ms; (viii) 1-5 ms; (ix) 5-10 ms; and (x) 10-20 ms.

30. A mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation trapping DC voltages are supplied to some of said electrodes so that ions are confined in two or more axial DC potential wells.

31. A mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation a V-shaped, sinusoidal, curved, stepped or linear axial DC potential profile is maintained along at least a portion of said fragmentation cell.

32. A mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation an upstream portion of the fragmentation cell continues to receive ions into the fragmentation cell whilst a downstream portion of the fragmentation cell separated from the upstream portion by a potential barrier stores and periodically releases ions.

33. A mass spectrometer as claimed in claim 32, wherein said upstream portion of the fragmentation cell has a length which is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the total length of the fragmentation cell.

34. A mass spectrometer as claimed in claim 32, wherein said downstream portion of the fragmentation cell has a length which is less than or equal to 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the total length of the fragmentation cell.

35. A mass spectrometer as claimed in claim 32, wherein the downstream portion of the fragmentation cell is shorter than the upstream portion of the fragmentation cell.

36. A mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation an AC or RF voltage is applied to at least some of said electrodes and the peak amplitude of said AC or RF voltage is varied.

37. A mass spectrometer as claimed in claim 36, wherein the peak amplitude of said AC or RF voltage is increased in time.

38. A mass spectrometer as claimed in claim 36, wherein when ions having a mass to charge ratio <500, <400, <300, <200, <100, or <50 are admitted into said fragmentation cell the peak amplitude of said AC or RF voltage is .ltoreq.200 .sub.Vpp, 150 V.sub.Pp, 100 V.sub.Pp, or 60 V.sub.Pp.

39. A mass spectrometer as claimed in claim 36, wherein when ions having a mass to charge ratio >500, >600, >700, >800, >900, or >1000 are admitted into said fragmentation cell the peak amplitude of said AC or RF voltage is .gtoreq.100 V.sub.Pp, .gtoreq.150 V.sub.Pp, .gtoreq.200 V.sub.Pp, .gtoreq.250 V.sub.Pp, or .gtoreq.300 V.sub.Pp.

40. A method of mass spectrometry, comprising: fragmenting ions in a fragmentation cell, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of said electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient is maintained in use along at least a portion of the length of said fragmentation cell.

Description

BACKGROUND OF THE INVENTION

The present invention relates to mass spectrometers.

In many tandem mass spectrometers ions are fragmented in a collision or fragmentation cell. A known fragmentation cell comprises a multipole (e.g. a quadrupole or hexapole) rod set wherein adjacent rods are connected to opposite phases of an RF voltage supply. The quadrupole or hexapole collision cell is housed in a cylindrical housing which is open at an upstream end and at a downstream end to allow ions to enter and exit the collision cell. The housing includes a gas inlet port through which a collision or buffer gas, typically nitrogen or argon, is introduced into the collision cell. The collision cell is maintained at a pressure of 10.sup.-3 -10.sup.-2 mbar.

Ions entering the collision cell are arranged to be sufficiently energetic so that when they collide with the collision or buffer gas at least some of the ions will fragment into daughter or fragment ions by means of Collisional Induced Dissociation/Decomposition ("CID"). Ions in the collision cell will also become thermalised after they have undergone a few collisions i.e. their kinetic energy will be considerably reduced, and this leads to greater radial confinement of the ions in the presence of the RF electric field. In order to ensure that ions are sufficiently energetic so as to fragment when entering the collision cell, the collision cell is typically maintained at a DC potential which is offset from that of the ion source by approximately -30V DC or more (for positive ions). Once ions have fragmented and have been thermalised within the collision cell, their low kinetic energy is such that they will tend to remain within the collision cell. In practice, ions are observed to exit the collision cell after a relatively long period of time, and this is believed to be due to the effects of diffusion and the repulsive effect of further ions being admitted into the collision cell.

Accordingly, one of the problems associated with the known collision cell is that ions tend to have a relatively long residence time within the collision cell. This is problematic for certain types of mass spectrometry methods since it is necessary to wait until ions have exited the collision cell before further ions are admitted into it. For example, in MS/MS (i.e. fragmentation) modes of operation if a quadrupole mass filter Q1 (MS1) upstream of a collision cell Q2 is scanned rapidly compared to the typical empty time (.about.30 ms) of ions to exit the collision cell Q2, then the peaks in the resulting parent ion scanning mass spectrum will suffer from peak tailing towards higher mass and thus the resulting mass spectrum will suffer from relatively poor resolution. An example of this is shown in FIG. 16(a).

Similarly, in Multiple Reaction Monitoring (MRM) experiments the upstream quadrupole mass filter Q1 (MS1) is switched rapidly to cyclically transmit a number of parent ions (e.g. P1, P2 . . . Pn) in a multiplexed manner, and the long empty times of ions to exit the collision cell Q2 may result in cross-talk between the various channels.

Long empty times of ions to exit the collision cell Q2 is also problematic when the mass spectrometer is being used in on-line chromatography applications since each peak only elutes over a short period of time and the mass spectrometer will have to acquire data very rapidly if a full parent (precursor) ion spectrum is desired.

It is therefore desired to provide an improved collision or fragmentation cell for use in a mass spectrometer which does not suffer from some or all of the problems discussed above.

SUMMARY OF THE INVENTION

According to a first aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell.

The preferred collision or fragmentation cell differs from a conventional multipole collision cell in that instead of comprising four or six elongated rod electrodes, the fragmentation cell comprises a number (e.g. typically >100) of ring, annular or plate like electrodes having apertures, preferably circular, through which ions are transmitted. Furthermore, an axial DC voltage gradient is preferably maintained across at least a portion of the length of the fragmentation cell, preferably the whole length of the fragmentation cell.

The fragmentation cell according to the preferred embodiment is capable of being emptied of and filled with ions much faster than a conventional collision cell. Mass spectra obtained using the preferred fragmentation cell exhibit improved resolution and greater sensitivity.

The fragmentation cell may comprise 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150, or >150 electrodes. The fragmentation cell may have a length <5 cm, 5-10 cm, 10-15 cm, 15-20 cm, 20-25 cm, 25-30 cm, or >30 cm. Preferably, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the electrodes are connected to both a DC and an AC or RF voltage supply. According to a one embodiment, an axial DC voltage difference of approximately 3V may be maintained along the whole length of the fragmentation cell (i.e. for positive ions, electrodes at the downstream end of the fragmentation cell are maintained at a DC voltage approximately 3V below electrodes at the upstream end of the fragmentation cell). In other embodiments the axial DC voltage difference maintained along at least a portion, preferably the whole length, of the fragmentation cell is 0.1-0.5 V, 0.5-1.0 V, 1.0-1.5 V, 1.5-2.0 V, 2.0-2.5 V, 2.5-3.0 V, 3.0-3.5 V, 3.5-4.0 V, 4.0-4.5 V, 4.5-5.0 V, 5.0-5.5 V, 5.5-6.0 V, 6.0-6.5 V, 6.5-7.0 V, 7.0-7.5 V, 7.5-8.0 V, 8.0-8.5 V, 8.5-9.0 V, 9.0-9.5 V, 9.5-10.0 V or >10V.

In terms of V/cm, the axial DC voltage gradient maintained along at least a portion of the fragmentation cell, and preferably along the whole length of the collision cell, may be 0.01-0.05 V/cm, 0.05-0.10 V/cm, 0.10-0.15 V/cm, 0.15-0.20 V/cm, 0.20-0.25 V/cm, 0.25-0.30 V/cm, 0.30-0.35 V/cm, 0.35-0.40 V/cm, 0.40-0.45 V/cm, 0.45-0.50 V/cm, 0.50-0.60 V/cm, 0.60-0.70 V/cm, 0.70-0.80 V/cm, 0.80-0.90 V/cm, 0.90-1.0 V/cm, 1.0-1.5 V/cm, 1.5-2.0 V/cm, 2.0-2.5 V/cm, 2.5-3.0 V/cm or >3.0 V/cm.

The voltage gradient may be a linear voltage gradient, or the voltage gradient may have a stepped or curved stepped profile similar to that shown in FIG. 4. The term "voltage gradient" should be construed broadly to cover embodiments wherein the DC voltage offset of electrodes along the length of the fragmentation cell relative to the DC potential of the ion source varies at different points along the length of the fragmentation cell. This term should not, however, be construed to include arrangements wherein all the electrodes forming the fragmentation cell are maintained at substantially the same DC potential.

According to the preferred embodiment, the electrodes forming the fragmentation cell are supplied with an AC or RF voltage which can be considered to be superimposed upon the DC potential supplied to the electrodes. Preferably, adjacent electrodes are connected to opposite phases of an AC or RF supply but according to other less preferred embodiments adjacent electrodes may be connected to different phases of the AC or RF supply i.e. voltage supplies having more than two phases are contemplated. Furthermore, although according to the preferred embodiment the AC or RF voltage supplied to the electrodes has a sinusoidal waveform (with a frequency 0.1-3.0 MHz, preferably 1.75 MHz), non-sinusoidal waveforms including square waves may be supplied to the electrodes.

According to a particularly preferred embodiment, the fragmentation cell may comprise a plurality of segments. In one embodiment fifteen segments are provided. Each segment comprises a plurality of electrodes, with preferably either eight or ten electrodes per segment. Each electrode has an aperture through which ions are transmitted. The diameter of the apertures of at least 50% of the electrodes forming the fragmentation cell is preferably .ltoreq.10 mm, .ltoreq.9 mm, .ltoreq.8 mm, .ltoreq.7 mm, .ltoreq.6 mm, .ltoreq.5 mm, .ltoreq.4 mm, .ltoreq.3 mm, .ltoreq.2 mm, or .ltoreq.1 mm. The thickness of at least 50% of the electrodes forming the fragmentation cell is preferably .ltoreq.3 mm, .ltoreq.2.5 mm, .ltoreq.2.0 mm, .ltoreq.1.5 mm, .ltoreq.1.0 mm, or .ltoreq.0.5 mm. Preferably, at least 50%, 60%, 70%, 80%, 90% or 95% of the electrodes forming the fragmentation cell have apertures which are substantially the same size or area. All the electrodes in a particular segment are preferably maintained at substantially the same DC potential, but adjacent electrodes in a segment are preferably supplied with different or opposite phases of an AC or RF voltage.

In an embodiment, ions may be trapped within the fragmentation cell in a mode of operation. Embodiments are contemplated wherein ions may be trapped in a downstream portion of the fragmentation cell whilst ions may be continually admitted into an upstream portion of the fragmentation cell. V-shaped axial DC potential profiles may be used to accelerate and trap ions within the collision cell.

The fragmentation cell is preferably maintained, in use, at a pressure >1.0.times.10.sup.-3 mbar, >5.0.times.10.sup.-3 mbar, >1.0.times.10.sup.-2 mbar 10.sup.-3 -10.sup.-2 mbar, or 10.sup.-4 -10.sup.-1 mbar.

The mass spectrometer preferably comprises a continuous ion source, further preferably an atmospheric pressure ion source, although other ion sources are contemplated. Electrospray ("ESI"), Atmospheric Pressure Chemical Ionisation ("APCI"), Atmospheric Pressure Photo Ionisation ("APPI"), Matrix Assisted Laser Desorption Ionisation ("MALDI"), non-matrix assisted Laser Desorption Ionisation, Inductively Coupled Plasma ("ICP"), Electron Impact ("EI") and Chemical Ionisation ("CI") ion sources may be provided.

The fragmentation cell preferably comprises a housing having an upstream opening for allowing ions to enter the fragmentation cell and a downstream opening for allowing ions to exit the fragmentation cell.

According to a second aspect of the present invention, there is provided a mass spectrometer comprising: an ion source; one or more ion guides; a first quadrupole mass filter; a fragmentation cell for fragmenting ions, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell; a second quadrupole mass filter; and a detector.

According to a third aspect of the present invention, there is provided a mass spectrometer comprising: an ion source; one or more ion guides; a quadrupole mass filter; a fragmentation cell for fragmenting ions, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell; and a time of flight mass analyser.

Preferably, the fragmentation cell comprises a plurality of segments, each segment comprising a plurality of electrodes having apertures through which ions are transmitted and wherein all the electrodes in a segment are maintained at substantially the same DC potential and wherein adjacent electrodes are supplied with different phases of an AC or RF voltage.

The one or more ion guides may comprise one or more AC or RF only ion tunnel ion guides (wherein at least 90% of the electrodes have apertures which are substantially the same size) and/or one or more hexapole ion guides.

According to a fourth aspect of the present invention, there is provided a mass spectrometer comprising: a first mass filter/analyser; a fragmentation cell for fragmenting ions, the fragmentation cell being arranged downstream of the first mass filter/analyser and comprising at least 20 electrodes having apertures through which ions are transmitted in use, wherein at least 75% of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein a non-zero axial DC voltage gradient or difference is maintained in use along at least 75% of the length of the fragmentation cell; and a second mass filter/analyser arranged downstream of the fragmentation cell.

Preferably, the first mass filter/analyser comprises a quadruople mass filter/analyser and the second mass filter comprises a quadrupole mass filter/analyser or a time of flight mass analyser.

According to a fifth aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell comprising .gtoreq.10 ring or plate electrodes having substantially similar internal apertures between 2-10 mm in diameter arranged in a housing having a buffer gas inlet port, wherein a buffer gas is introduced in use into the fragmentation cell at a pressure of 10.sup.-4 -10.sup.-1 mbar and wherein a DC potential gradient or difference is maintained, in use, along the length of the fragmentation cell.

Preferably, the mass spectrometer further comprises an ion source and ion optics upstream of the fragmentation cell, wherein the ion source and/or the ion optics are maintained at potentials such that at least some of the ions entering the fragmentation cell have, in use, an energy .gtoreq.10 eV for a singly charged ion such that they are caused to fragment.

According to a sixth aspect of the present invention, there is provided a mass spectrometer comprising: an ion source; a fragmentation cell for fragmenting ions, the fragmentation cell comprising at least ten plate-like electrodes arranged substantially perpendicular to the longitudinal axis of the fragmentation cell, each electrode having an aperture therein through which ions are transmitted in use, the fragmentation cell being supplied in use with a collision gas at a pressure .gtoreq.10.sup.-3 mbar, wherein adjacent electrodes are connected to different phases of an AC or RF voltage supply and a DC potential gradient .gtoreq.0.01 V/cm is maintained over at least 20% of the length of the fragmentation cell; and ion optics arranged between the ion source and the fragmentation cell; wherein in a mode of operation the ion source, ion optics and fragmentation cell are maintained at potentials such that singly charged ions are caused to have an energy .gtoreq.10 eV upon entering the fragmentation cell so that at least some of the ions fragment into daughter ions.

According to a seventh aspect of the present invention, there is provided a mass spectrometer comprising: a collision or fragmentation cell comprising at least three segments, each segment comprising at least four electrodes having substantially similar sized apertures through which ions are transmitted in use; wherein in a mode of operation: electrodes in a first segment are maintained at substantially the same first DC potential but adjacent electrodes are supplied with different phases of an AC or RF voltage supply; electrodes in a second segment are maintained at substantially the same second DC potential but adjacent electrodes are supplied with different phases of an AC or RF voltage supply; electrodes in a third segment are maintained at substantially the same third DC potential but adjacent electrodes are supplied with different phases of an AC or RF voltage supply; wherein the first, second and third DC potentials are all different.

According to an eighth aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to an AC or RF voltage supply.

Preferably, at least some of the electrodes are also connected to a DC voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell.

According to a ninth aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein in a mode of operation at least a portion of the fragmentation cell is maintained at a DC potential so as to prevent ions from exiting the fragmentation cell.

According to a tenth aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein the empty time taken for ions to exit the fragmentation cell is selected from the group comprising: (i) .ltoreq.0.5 ms; (ii) .ltoreq.1.0 ms; (iii) .ltoreq.5 ms; (iv) .ltoreq.10 ms; (v) .ltoreq.20 ms; (vi) 0.01-0.5 ms; (vii) 0.5-1 ms; (viii) 1-5 ms; (ix) 5-10 ms; and (x) 10-20 ms.

According to an eleventh aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation trapping DC voltages are supplied to some of the electrodes so that ions are confined in two or more axial DC potential wells.

According to a twelfth aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation a V-shaped, sinusoidal, curved, stepped or linear axial DC potential profile is maintained along at least a portion, preferably at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the length of the fragmentation cell.

According to a thirteenth aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation an upstream portion of the fragmentation cell continues to receive ions into the fragmentation cell whilst a downstream portion of the fragmentation cell separated from the upstream portion by a potential barrier stores and periodically releases ions.

Preferably, the upstream portion of the fragmentation cell has a length which is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the total length of the fragmentation cell. Preferably, the downstream portion of the fragmentation cell has a length which is less than or equal to 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the total length of the fragmentation cell. Further preferably, the downstream portion of the fragmentation cell is shorter than the upstream portion of the fragmentation cell.

According to a fourteenth aspect of the present invention, there is provided a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation an AC or RF voltage is applied to at least some of said electrodes and the peak amplitude of said AC or RF voltage is varied.

Preferably, the peak amplitude of the AC or RF voltage is increased in time.

Preferably, when ions having a mass to charge ratio <500, <400, <300, <200, <100, or <50 are admitted into the fragmentation cell the peak amplitude of the AC or RF voltage is .gtoreq.200 V.sub.Pp, .gtoreq.150 V.sub.Pp, .gtoreq.100 V.sub.Pp, or .gtoreq.60 V.sub.Pp.

Preferably, when ions having a mass to charge ratio >500, >600, >700, >800, >900, or >1000 are admitted into the fragmentation cell the peak amplitude of the AC or RF voltage is .gtoreq.100 V.sub.Pp, .gtoreq.150 V.sub.Pp, .gtoreq.200 V.sub.Pp, .gtoreq.250 V.sub.Pp, or .gtoreq.300 V.sub.Pp.

According to a fifteenth aspect of the present invention, there is provided a method of mass spectrometry, comprising: fragmenting ions in a fragmentation cell, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell.

BRIEF DESCRIPTION OF THE DRAWINGS

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

FIG. 1(a) shows a preferred ion tunnel fragmentation cell;

FIG. 1(b) shows another ion tunnel fragmentation cell which is additionally capable of confining ions within the fragmentation cell;

FIG. 2 shows another ion tunnel fragmentation cell wherein the DC voltage supply to each ion tunnel segment is individually controllable;

FIG. 3(a) shows a front view of an ion tunnel segment;

FIG. 3(b) shows a side view of an upper ion tunnel section;

FIG. 3(c) shows a plan view of an ion tunnel segment;

FIG. 4 shows an axial DC potential profile as a function of distance at a central portion of an ion tunnel fragmentation cell;

FIG. 5 shows a potential energy surface across a number of ion tunnel segments at a central portion of an ion tunnel fragmentation cell;

FIG. 6 shows a portion of an axial DC potential profile for a fragmentation cell being operated in an trapping mode without an accelerating axial DC potential gradient being applied along the length of the fragmentation cell;

FIG. 7(a) shows an axial DC potential profile for a fragmentation cell operated in a "fill" mode of operation;

FIG. 7(b) shows a corresponding "closed" mode of operation;

FIG. 7(c) shows a corresponding "empty" mode of operation;

FIG. 8 shows the effect of various applied axial DC voltage gradients on the intensity of daughter ions observed in a parent ion scan;

FIG. 9 shows the effect of acquisition time on signal intensity;

FIG. 10 shows how the transmission of ions varies as a function of mass to charge ratio and the amplitude of the RF voltage in the absence of collision gas in the fragmentation cell;

FIG. 11 shows how the transmission of ions varies as a function of mass to charge ratio and the amplitude of the RF voltage with collision gas present in the fragmentation cell but with the fragmentation cell being operated in a non-fragmenting mode;

FIG. 12(a) shows how the transmission of ions having a mass to charge ratio of 117 varies as a function of applied axial DC voltage gradient and the amplitude of the RF voltage;

FIG. 12(b) shows corresponding transmission characteristics for ions having a mass charge ratios of 609;

FIG. 12(c) shows corresponding transmission characteristics for ions having a mass charge ratios of 1081;

FIG. 12(d) shows corresponding transmission characteristics for ions having a mass charge ratios of 2034;

FIG. 13 shows how the transmission of daughter ions having a mass to charge ratio of 173 (resulting from the fragmentation of parent ions having a mass to charge ratio of 2872) varies as a function of the amplitude of the RF voltage when axial DC voltage gradients of 0V and 3V are applied;

FIG. 14 shows how the empty time of the ion tunnel fragmentation cell varies as a function of applied DC voltage gradient;

FIG. 15(a) shows a neutral loss spectra of S-desmethyl metabolite formed during microsomal incubation of Rabeprazole for a conventional hexapole collision cell;

FIG. 15(b) shows a neutral loss spectra of S-desmethyl metabolite formed during microsomal incubation of Rabeprazole for a fragmentation cell according to the preferred embodiment;

FIG. 16(a) shows a parent ion spectra of Sulphone metabolite formed during microsomal incubation of Rabeprazole for a conventional hexapole collision cell;

FIG. 16(b) shows a parent ion spectra of Sulphone metabolite formed during microsomal incubation of Rabeprazole for a fragmentation cell according to the preferred embodiment;

FIG. 17(a) shows extracted ion chromatograms of Sulphone metabolite formed during microsomal incubation of Rabeprazole for a conventional hexapole collision cell; and

FIG. 17(b) shows extracted ion chromatograms of Sulphone metabolite formed during microsomal incubation of Rabeprazole for a fragmentation cell according to the preferred embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A preferred ion tunnel collision or fragmentation cell will now be described in relation to FIGS. 1 and 2. The ion tunnel fragmentation cell 1 comprises a reasonably gas tight housing having a relatively small entrance aperture 2 and a relatively small exit aperture 3. The entrance and exit apertures 2,3 are preferably 2.2 mm diameter substantially circular apertures. The plates forming the entrance and/or exit apertures 2,3 may be connected to independent programmable DC voltage supplies (not shown).

Between the plate forming the entrance aperture 2 and the plate forming the exit aperture 3 are arranged a number of electrically isolated ion tunnel segments 4a,4b,4c. In one embodiment fifteen segments 4a,4b,4c are provided. Each ion tunnel segment 4a;4b;4c comprises two interleaved and electrically isolated sections i.e. an upper and lower section. The ion tunnel segment 4a closest to the entrance aperture 2 preferably comprises ten electrodes (with five electrodes in each section) and the remaining ion tunnel segments 4b,4c preferably each comprise eight electrodes (with four electrodes in each section). All the electrodes are preferably substantially similar in that they have a central substantially circular aperture (preferably 5 mm in diameter) through which ions are transmitted. The entrance and exit apertures 2,3 are preferably smaller (e.g. 2.2 mm in diameter) than the apertures in the electrodes, and this helps to reduce the amount of collision gas leaking out of the fragmentation cell 1 into the vacuum chamber containing the fragmentation cell 1 which is preferably maintained at a lower pressure e.g. 10.sup.-4 mbar or less.

All the ion tunnel segments 4a,4b,4c are preferably connected to the same AC or RF voltage supply, but different segments 4a;4b;4c may be provided with different DC voltages. The two sections forming an ion tunnel segment 4a;4b;4c are connected to different, preferably opposite, phases of the AC or RF voltage supply.

A single ion tunnel section is shown in greater detail in FIGS. 3(a)-(c). The ion tunnel section has four (or five) electrodes 5, each electrode 5 having a 5 mm diameter central aperture 6. The four (or five) electrodes 5 depend or extend from a common bar or spine 7 and are preferably truncated at the opposite end to the bar 7 as shown in FIG. 3(a). Each electrode 5 is typically 0.5 mm thick. Two ion tunnel sections are interlocked or interleaved to provide a total of eight (or ten) electrodes 5 in an ion tunnel segment 4a;4b;4c with a 1 mm inter-electrode spacing once the two sections have been interleaved. All the eight (or ten) electrodes 5 in an ion tunnel segment 4a;4b;4c comprised of two separate sections are preferably maintained at substantially the same DC voltage. Adjacent electrodes in an ion tunnel segment 4a;4b;4c comprised of two interleaved sections are connected to different, preferably opposite, phases of an AC or RF voltage supply i.e. one section of an ion tunnel segment 4a;4b;4c is connected to one phase (RF+) and the other section of the ion tunnel segment 4a;4b;4c is connected to another phase (RF-).

Each ion tunnel segment 4a;4b;4c is mounted on a machined PEEK support that acts as the support for the entire assembly. Individual ion tunnel sections are located and fixed to the PEEK support by means of a dowel and a screw. The screw is also used to provide the electrical connection to the ion tunnel section. The PEEK supports are held in the correct orientation by two stainless steel plates attached to the PEEK supports using screws and located correctly using dowels. These plates are electrically isolated and have a voltage applied to them.

Collision gas is supplied to the fragmentation cell 1 via a 4.5 mm ID tube. Another tube may be connected to a vacuum gauge allowing the pressure in the fragmentation cell 1 to be monitored.

The electrical connections shown in FIG. 1(a) are such that a substantially regular stepped axial accelerating DC electric field is provided along the length of the fragmentation cell 1 using two programmable DC power supplies DC1 and DC2 and a resistor potential divider network of 1 M.OMEGA. resistors. An AC or RF voltage supply provides phase (RF+) and anti-phase (RF-) voltages at a frequency of preferably 1.75 MHz and is coupled to the ion tunnel sections 4a,4b,4c via capacitors which are preferably identical in value (100 pF). According to other embodiments the frequency may be in the range of 0.1-3.0 MHz. Four 10 .mu.H inductors are provided in the DC supply rails to reduce any RF feedback onto the DC supplies. A regular stepped axial DC voltage gradient is provided if all the resistors are of the same value. Similarly, the same AC or RF voltage is supplied to all the electrodes if all the capacitors are the same value. FIG. 4 shows how, in one embodiment, the axial DC potential varies across a 10 cm central portion of the ion tunnel fragmentation cell 1. The inter-segment voltage step in this particular embodiment is -1V. However, according to more preferred embodiments lower voltage steps of e.g. approximately -0.2V may be used. FIG. 5 shows a potential energy surface across several ion tunnel segments 4b at a central portion of the ion tunnel fragmentation cell 1. As can be seen, the potential energy profile is such that ions will cascade from one ion tunnel segment to the next.

FIG. 1(b) shows another embodiment wherein the ion tunnel fragmentation cell 1 also traps, accumulates or otherwise confines ions within the fragmentation cell 1. In this embodiment, the DC voltage applied to the final ion tunnel segment 4c (i.e. that closest and adjacent to the exit aperture 3) is independently controllable and can in one mode of operation be maintained at a relatively high DC blocking or trapping potential (DC3) which is more positive for positively charged ions (and vice versa for negatively charged ions) than the preceding ion tunnel segment(s) 4b. Other embodiments are also contemplated wherein other ion tunnel segments 4a,4b may alternatively and/or additionally be maintained at a relatively high trapping potential. When the final ion tunnel segment 4c is being used to trap ions within the fragmentation cell 1, an AC or RF voltage may or may not be applied to the final ion tunnel segment 4c.

The DC voltage supplied to the plates forming the entrance and exit apertures 2,3 is also preferably independently controllable and preferably no AC or RF voltage is supplied to these plates. Embodiments are also contemplated wherein a relatively high DC trapping potential may be applied to the plates forming entrance and/or exit aperture 2,3 in addition to or instead of a trapping potential being supplied to one or more ion tunnel segments such as at least the final ion tunnel segment 4c.

In order to release ions from confinement within the fragmentation cell 1, the DC trapping potential applied to e.g. the final ion tunnel segment 4c or to the plate forming the exit aperture 3 is preferably momentarily dropped or varied, preferably in a pulsed manner. In one embodiment the DC voltage may be dropped to approximately the same DC voltage as is being applied to neighbouring ion tunnel segment(s) 4b. Embodiments are also contemplated wherein the voltage may be dropped below that of neighbouring ion tunnel segment(s) so as to help accelerate ions out of the fragmentation cell 1. In another embodiment a V-shaped trapping potential may be applied which is then changed to a linear profile having a negative gradient in order to cause ions to be accelerated out of the fragmentation cell 1. The voltage on the plate forming the exit aperture 3 can also be set to a DC potential such as to cause ions to be accelerated out of the fragmentation cell 1.

Other less preferred embodiments are contemplated wherein no axial DC voltage difference or gradient is applied or maintained along the length of the fragmentation cell 1. FIG. 6, for example, shows how the DC potential may vary along a portion of the length of the fragmentation cell 1 when no axial DC field is applied and the fragmentation cell 1 is acting in a trapping or accumulation mode. In this figure, 0 mm corresponds to the midpoint of the gap between the fourteenth 4b and fifteenth (and final) 4c ion tunnel segments. In this particular example, the blocking potential was set to +5V (for positive ions) and was applied to the last (fifteenth) ion tunnel segment 4c only. The preceding fourteen ion tunnel segments 4a,4b had a potential of -1V applied thereto. The plate forming the entrance aperture 2 was maintained at 0V DC and the plate forming the exit aperture 3 was maintained at -1V.

More complex modes of operation are contemplated wherein two or more trapping potentials may be used to isolate one or more section(s) of the ion tunnel fragmentation cell 1. For example, FIG. 7(a) shows a portion of the axial DC potential profile for a fragmentation cell 1 according to one embodiment operated in a "fill" mode of operation, FIG. 7(b) shows a corresponding "closed" mode of operation, and FIG. 7(c) shows a corresponding "empty" mode of operation. By sequencing the potentials, the fragmentation cell 1 may be opened, closed and then emptied in a short defined pulse. In the example shown in the figures, 0 mm corresponds to the midpoint of the gap between the tenth and eleventh ion tunnel segments 4b. The first nine segments 4a,4b are held at -1V, the tenth and fifteenth segments 4b act as potential barriers and ions are trapped within the eleventh, twelfth, thirteenth and fourteenth segments 4b. The trap segments are held at a higher DC potential (+5V) than the other segments 4b. When closed the potential barriers are