Mass spectrometer with reduced potential drop

Abstract

A method of mass spectrometry is disclosed comprising providing a first device and a second device disposed downstream of the first device. The method further comprises introducing a potential difference between the exit of the first device and the entrance of the second device and reducing the total potential drop across the first and second devices by applying a reverse axial electric field to the first device and/or the second device. Ions are driven through the first device and/or the second device against the reverse axial electric field.

Claims

1. A method of mass spectrometry comprising: providing a first device and a second device disposed downstream of said first device; introducing a potential difference between the exit of said first device and the entrance of said second device, wherein ions are accelerated through the potential difference into a fragmentation or reaction device such that the potential difference at least in part determines a collision energy of ions entering the fragmentation or reaction device; reducing the total potential drop across the first and second devices by applying a reverse axial electric field to said first device and/or said second device; and driving ions through said first device and/or said second device against said reverse axial electric field.

2. A method as claimed in claim 1, wherein the potential drop between the entrance of said first device and the exit of said second device is less than said potential difference between the exit of said first device and the entrance of said second device.

3. A method as claimed in claim 1, comprising adjusting said reverse axial field to adjust said potential difference.

4. A method as claimed in claim 1, wherein said second device comprises said fragmentation or reaction device.

5. A method as claimed in claim 1, further comprising controlling the collision energy of ions entering said fragmentation or reaction device by adjusting said reverse axial electric field.

6. A method as claimed in claim 1, further comprising providing a continuous beam of ions to said first device and said second device.

7. A method as claimed in claim 1, wherein driving ions through said first device and/or said second device against said reverse axial electric field comprises: (i) applying one or more transient DC voltages or potentials or one or more DC voltage or potential waveforms to a plurality of axial segments constituting said first and/or second device; and/or (ii) applying one or more AC or RF voltages or potentials or one or more AC or RF voltage or potential waveforms to a plurality of axial segments constituting said first and/or second device; and/or (iii) driving ions through said first device and/or said second device against said reverse axial electric field using a gas flow.

8. A method as claimed in claim 1, further comprising driving ions through said first device and/or said second device against said reverse axial electric field without ion mobility separation.

9. A method of mass spectrometry comprising: reducing the potential drop between the entrance of a first device and the exit of a second device disposed downstream of the first device by applying a reverse axial electric field to said first device and/or said second device; and driving ions through said first device and/or said second device against said reverse axial electric field, wherein either: (i) the reverse axial electric field is applied to the second device and the method further comprises introducing a forward axial electric field across the first device so that ions are caused to separate according to their ion mobility in the first device; or (ii) wherein said reverse axial electric field is applied to the first device and the method further comprises introducing a forward axial electric field across the second device so that ions are caused to separate according to their ion mobility in the second device.

10. A method as claimed in claim 9, further comprising providing a continuous beam of ions to said first device and said second device.

11. A method of mass spectrometry as claimed in claim 9, wherein driving ions through said first device and/or said second device against said reverse axial electric field comprises: (i) applying one or more transient DC voltages or potentials or one or more DC voltage or potential waveforms to a plurality of axial segments constituting said second device; and/or (ii) applying one or more AC or RF voltages or potentials or one or more AC or RF voltage or potential waveforms to a plurality of axial segments constituting said second device.

12. A method as claimed in claim 9, further comprising driving ions through said first device and/or said second device against said reverse axial electric field using a gas flow.

13. A mass spectrometer comprising: a first device and a second device disposed downstream of the first device, wherein either: (i) a potential difference is applied between the exit of said first device and the entrance of said second device, wherein ions are accelerated through the potential difference into a fragmentation or reaction device such that the potential difference at least in part determines a collision energy of ions entering the fragmentation or reaction device and the mass spectrometer further comprises a device arranged and adapted to reduce the potential drop between the entrance of the first device and the exit of the second device by applying a reverse axial electric field to said first device and/or said second device; or (ii) a forward axial electric field is applied across either the first device or second device so that ions are caused to separate according to their ion mobility in that device, and a reverse axial electric field is applied to the other of the first device and second device in order to reduce the potential drop between the entrance of the first device and the exit of the second device; and the mass spectrometer further comprising: a device arranged and adapted to drive ions through said first device and/or said second device against said reverse axial electric field.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Various embodiments together with other arrangements given for illustrative purposes only will now be described, by way of example only, and with reference to the accompanying drawings in which:

(2) FIG. 1 shows a mass spectrometer being operated in a non-fragmentation mode according to a conventional approach;

(3) FIG. 2 shows a mass spectrometer being operated in a fragmentation mode according to a conventional approach;

(4) FIG. 3 shows a mass spectrometer being operated in a fragmentation mode according to an embodiment;

(5) FIG. 4 shows a mass spectrometer being operated in a fragmentation mode according to another embodiment; and

(6) FIG. 5 shows a typical arrangement of components within a mass spectrometer.

DETAILED DESCRIPTION

(7) Various conventional modes of operation will first be described.

(8) FIG. 1 shows a conventional mass spectrometer being operated in a non-fragmentation mode. The position along the instrument of various devices (going downstream from left to right) and the electric potential at that position (represented by the vertical axis) are illustrated. The dotted line represents the electrical breakdown limit. The mass spectrometer comprises a first upstream device 1, a second upstream device 2, a gas-filled collision cell 3 and a downstream device 4.

(9) In FIG. 1 the potentials are arranged to efficiently transmit ions along the device with minimal fragmentation. A slight potential drop is introduced between adjacent components. However, ions are passed from the second upstream device 2 into the collision cell 3 with insufficient energy to cause fragmentation. Without such focusing voltages, ions may effectively slow to a halt within the mass spectrometer.

(10) It can be seen from FIG. 1 that the total potential drop along the length of the instrument is relatively small and that all of the components are held at relatively low absolute potentials below the limit of electrical breakdown as represented by the dotted line.

(11) A conventional mass spectrometer being operated in a conventional fragmentation mode will now be described with reference to FIG. 2. FIG. 2 illustrates the mass spectrometer as shown in FIG. 1 but arranged to perform collision-induced dissociation (CID) of ions.

(12) To induce fragmentation, a potential difference is introduced between the upstream devices 1,2 and the collision cell 3 by raising the absolute potential applied to the first upstream device 1 and the second upstream device 2. Ions in the second upstream device 2 will be accelerated through the potential difference between the exit of the second upstream device 2 and the entrance of the collision cell 3 into the collision cell 3. The collision energy is primarily determined by this potential difference and the degree of fragmentation can thus be controlled by adjusting the potential difference between the collision cell 3 and the upstream devices.

(13) It is important to note that all of the devices upstream of the collision cell 3 must be raised at least by an amount corresponding to the collision energy to ensure that parent or precursor ions are efficiently transmitted to the collision cell 3 i.e. that the ions are transmitted from the first upstream device 1 to the second upstream device 2.

(14) Since the upstream devices 1,2 are required to track or float the collision energy, the total potential drop along the length of the instrument as shown in FIG. 2 is relatively large. It can be seen from FIG. 2 that the upstream devices 1,2 are now held at relatively high absolute potentials above the electrical breakdown limit.

(15) This cumulative effect may be compounded for instruments having additional upstream devices or additional upstream potential drops.

(16) A first example illustrating some of the advantages of the techniques of the various embodiments will now be described with reference to FIG. 3.

(17) FIG. 3 shows a similar instrument to that described above being operated in a fragmentation mode according to an embodiment and with like reference signs representing like components.

(18) The collision energy is determined by the potential difference between the exit of the second upstream device 2 and the entrance of the collision cell 3. However, in this embodiment the potential difference is introduced, at least in part, by applying a reverse axial DC electric field to the collision cell 3. The reverse axial electric field provides an increasing axial potential in the downstream direction so that the potential at the exit of the collision cell 3 is raised relative to the potential at the entrance. The potential drop defining the collision energy is therefore localised to region around the entrance of the collision cell 3.

(19) To transmit ions from the collision cell 3 to a downstream device 4 it is necessary to drive ions against the reverse axial electric field. The collision cell 3 may generally comprise a plurality of electrodes and is segmented in the axial direction so that independent transient DC potentials or voltage waveforms can be applied to each segment. The transient DC potentials or voltage waveforms applied to each segment generate a travelling wave 5 which moves in the axial direction and urges or propels ions up or against the potential gradient of the reverse axial electric field.

(20) Other means for driving ions against the reverse axial electric field include AC or RF pseudo-potential drives or gas flows.

(21) By using a reverse axial field in combination with a travelling wave 5, the requirement for the first upstream device 1, second upstream device 2 and downstream device 4 to track the collision energy is advantageously avoided. Thus, these devices can potentially remain static i.e. at essentially the same potentials as during the non-fragmentation mode depicted in FIG. 1. It can be seen that introducing a reverse axial electric field in this manner enables the total potential drop along the length of the instrument and hence the absolute potential of the upstream devices to be reduced.

(22) Another example illustrating some of the advantages of the techniques of the various embodiments will be described with reference to FIG. 4.

(23) In FIG. 4, a reverse axial DC electric field is applied to the second upstream device 2 and the collision cell 3 is held static. Ions may be driven against the reverse axial electric field in a similar manner to that described above, for instance using travelling DC voltage waves 5. Again, a potential difference is introduced between the exit of the second upstream device 2 and the entrance of the collision cell 3 without requiring the other devices to track the collision energy. Thus, similarly to the embodiment shown in FIG. 3, the total potential drop and absolute potentials are reduced relative to the conventional mass spectrometer as shown in FIG. 2.

(24) In the embodiments shown and described with reference to FIG. 3 and FIG. 4, the collision energy is controlled at least in part by adjusting the reverse axial electric field applied to the collision cell 3 or the second upstream device 2. However, other embodiments may employ a combination of any of the approaches described above. For instance, a reverse axial electric field may be applied to both the second upstream device 2 and the collision cell 3 to provide larger collision energies. Similarly, the potentials of the other upstream and downstream devices may be adjusted in addition to or in combination with the reverse axial electric field. This may be done in order to avoid introducing an overly steep reverse axial electric field gradient and/or to further increase the collision energy. In these embodiments the total potential drop along the instrument and/or absolute potentials of the upstream components are still reduced relative to the conventional mass spectrometer shown in FIG. 2.

(25) In the embodiments described above the upstream devices may be any typical mass spectrometer components including one or more ambient or sub-ambient ionisation sources, ion guides, RF confined intermediate pressure regions, fragmentation or reaction devices, ion mobility devices, ion focusing optics, mass to charge ratio filters such as quadrupole mass filters and mass to charge ratio separators such as ion traps or Time of Flight mass analysers. Similarly, the downstream devices may include one or more RF confined intermediate pressure regions, fragmentation or reaction devices, ion mobility devices, ion focusing optics, mass to charge ratio filters such as quadrupole mass filters and mass to charge ratio separators such as ion traps or Time of Flight mass analysers. Although a collision cell is illustrated, it is emphasised that the various embodiments may apply equally to other devices which introduce or require a potential drop.

(26) FIG. 5 shows a typical arrangement of mass spectrometer components to which the embodiments described above may apply. In this configuration, a continuous beam of ions is generated in an ion source and the beam of ions is then passed to a quadrupole device (second upstream device 2), a gas cell (collision cell 3) and an orthogonal acceleration Time of Flight mass analyser (downstream device 4).

(27) The number and order of these components is not intended to be limiting. Multiple devices may be combined and/or operated together within a single instrument to reduce the overall potential drop along an instrument. With reference to the embodiment shown in FIG. 3, the reverse axial electric field need not be provided directly adjacent to the local potential drop defining the collision energy. For example, the collision cell 3 may have no reverse axial electric field and a reverse axial electric field may be applied to a further non-illustrated component downstream of the collision cell 3.

(28) The principles of the various embodiments described above apply equally to other configurations of mass spectrometer including a potential drop. For instance, there may be a relatively large potential drop along the length of the drift tube of an ion mobility separation device. In a similar manner to the embodiments described above, the total potential drop along the instrument can be reduced by introducing a reverse axial DC field to a component upstream or downstream of the ion mobility separation device.

(29) Naturally, it is also possible to compensate for a reverse field gradient using one or more potential difference in an analogous or equivalent fashion. Indeed, it will be appreciated that the potential drop and the reverse field generally compensate each other to reduce the total potential drop.

(30) Although the present invention has been described with reference to particular examples and 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.