Mass spectrometer

Abstract

In a tandem mass spectrometer, when the measurement mode is switched between a positive ion measurement mode and a negative ion measurement mode, a DC offset voltage applied to a lens electrode to impart collision energy to an ion is temporarily switched to 0V (S1). After being maintained at 0V for a predetermined waiting time (S2), the voltage is changed to a DC offset voltage corresponding to a measurement mode which is used after the switching operation (S3). By such an operation, the voltage difference between the neighboring plate electrodes among the plate electrodes (171, 172, 173) included in the lens electrode can be decreased as compared to the case where the polarity of the DC offset voltage is immediately switched. Consequently, unintended electric discharge between the neighboring electrodes can be prevented.

Claims

1. A mass spectrometer capable of an MS/MS measurement, including a collision cell configured to dissociate an ion by collision induced dissociation, and a plurality of electrodes located at a frontward or rearward position from the collision cell and configured to be supplied with a DC offset voltage for imparting collision energy to an ion entering the collision cell, the mass spectrometer further comprising: a) a plurality of voltage generators configured to apply voltages to the plurality of electrodes, respectively; and b) a voltage controller configured to control the plurality of voltage generators in switching a polarity of the DC offset voltage along with a switching operation between a positive ion measurement mode and a negative ion measurement mode, in such a manner that each of the voltages applied to the plurality of electrodes is temporarily changed to zero from a DC offset voltage used immediately before the switching operation, then maintained at zero for a predetermined waiting time, and subsequently changed to a DC offset voltage to be used after the switching operation.

2. The mass spectrometer according to claim 1, further comprising: a time setter configured to allow a user to set the waiting time.

3. The mass spectrometer according to claim 2, further comprising: a quadrupole mass filter located on a front side of the collision cell and an orthogonal acceleration time-of-flight mass analyzer on a rear side of the collision cell.

4. The mass spectrometer according to claim 1, further comprising: a quadrupole mass filter located on a front side of the collision cell and an orthogonal acceleration time-of-flight mass analyzer on a rear side of the collision cell.

5. The mass spectrometer according to claim 1, wherein the waiting time is set to be longer than a discrepancy in timing of a switching operation of the polarity of the voltages applied to the plurality of electrodes.

6. The mass spectrometer according to claim 5, further comprising: a quadrupole mass filter located on a front side of the collision cell and an orthogonal acceleration time-of-flight mass analyzer on a rear side of the collision cell.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a schematic configuration diagram of a Q-TOF mass spectrometer as one embodiment of the present invention.

(2) FIG. 2 is a configuration diagram of the control system for a portion of the Q-TOF mass spectrometer according to the present embodiment.

(3) FIG. 3 is a flowchart of the voltage-polarity switching procedure for the switching operation between the positive ion measurement mode and the negative ion measurement mode in the Q-TOF mass spectrometer according to the present embodiment.

(4) FIG. 4 is a diagram showing one example of the waveform of the DC offset voltage for the switching operation from the positive ion measurement mode to the negative ion measurement mode in the Q-TOF mass spectrometer according to the present embodiment.

(5) FIG. 5 is a schematic configuration diagram of a section near the ion entrance opening of the collision cell in a conventional tandem mass spectrometer.

DESCRIPTION OF EMBODIMENTS

(6) A quadrupole time-of-flight (“Q-TOF”) mass spectrometer as one embodiment of the present invention is hereinafter described with reference to the attached drawings.

(7) FIG. 1 is a schematic configuration diagram of the Q-TOF mass spectrometer according to the present embodiment.

(8) The Q-TOF mass spectrometer according to the present embodiment has the configuration of a multi-stage differential pumping system including a chamber 1, within which first through third intermediate vacuum chambers 3, 4 and 5 are provided between an ionization chamber 2 maintained at substantially atmospheric pressure and a first analysis chamber 6 maintained at a high degree of vacuum. A second analysis chamber 7 maintained at an even higher degree of vacuum is also provided in a stage subsequent to the first analysis chamber 6.

(9) The ionization chamber 2 is provided with an ESI spray 10 for electrospray ionization (ESI). When a sample liquid containing a target compound is supplied to the ESI spray 10, the liquid is given imbalanced electric charges from the tip of the spray 10 and sprayed in the form of droplets, from which ions originating from the target compound are generated. It should be noted that the ionization method is not limited to this procedure.

(10) The various ions generated in the ionization chamber 2 are sent into the first intermediate vacuum chamber 3 through a heated capillary 11. The ions are subsequently converged by an ion guide 12 and sent into the second intermediate vacuum chamber 4 through a skimmer 13. The ion guide 12 in the present embodiment is a device called the “Q array” formed by a plurality of plate electrodes (see Patent Literature 2 or other related documents), although the type of ion guide 12 is not limited to this example. The ions are further converged by multipole ion guides 14 and 15, as well as sent through the second intermediate vacuum chamber 4 and the third intermediate vacuum chamber 5 into the first analysis chamber 6. The first analysis chamber 6 contains a quadrupole mass filter 16, a lens electrode 17 including a plurality of plate electrodes, and a collision cell 19 containing a quadrupole ion guide 18.

(11) The various ions derived from a sample are introduced into the quadrupole mass filter 16. When an MS/MS measurement is performed, only an ion having a specific mass-to-charge ratio corresponding to the voltage applied to the quadrupole mass filter 16 is allowed to pass through the quadrupole mass filter 16. This ion travels through the lens electrode 17 and is introduced into the collision cell 19 as the precursor ion. The precursor ion collides with the collision gas supplied from an outside source into the collision cell 19, whereby various product ions are generated. The lens electrode 17, which is an electrostatic lens formed by a plurality of plate electrodes 171-173 as shown in FIG. 5, is configured to converge ions by a DC electric field created by DC voltages applied to the plate electrodes 171-173.

(12) The product ions generated by dissociation exit from the collision cell 19 and are introduced into the second analysis chamber 7, being guided by the ion transport optical system 20 which is an electrostatic lens. The second analysis chamber 7 contains an orthogonal accelerator section 31 which is the ion ejection source, a flight space 30 having a reflector 32 and back plate 33, as well as an ion detector 34. The ions introduced into the orthogonal accelerator section 31 in the X-axis direction begin are accelerated in the Z-axis direction at a predetermined timing and begin to fly. The accelerated ions initially fly freely. After being returned by a reflective electric field created by the reflector 32 and back plate 33, the ions once more fly freely and arrive at the ion detector 34. The time of flight from the point in time where an ion departs from the orthogonal accelerator section 31 to the point in time where the ion arrives at the ion detector 34 depends on the mass-to-charge ratio of the ion. A data processing unit 40 receives detection signals from the ion detector 34, creates a time-of-flight spectrum based on the detection signals, and determines a mass spectrum by converting the time of flight into mass-to-charge ratio.

(13) When a measurement is performed in this Q-TOF mass spectrometer, predetermined voltages are respectively applied to the electrodes. To this end, voltage sources for generating voltages to be respectively applied to the electrodes are provided. The ion to be subjected to the measurement may be a positive ion or negative ion. The user selects which of the positive and negative measurement modes should be used for the measurement. Switching the measurement mode between the positive and negative ion measurement modes requires inverting the polarity of the voltages applied to the electrodes. The Q-TOF mass spectrometer according to the present embodiment performs a characteristic control in switching the measurement mode. This point is hereinafter described in detail.

(14) FIG. 2 is a configuration diagram of the control system for the main components of the Q-TOF mass spectrometer according to the present embodiment. FIG. 3 is a flowchart of the voltage-polarity switching procedure for the switching operation between the positive ion measurement mode and the negative ion measurement mode. FIG. 4 is a diagram showing one example of the waveform of the offset voltage for the switching operation from the positive ion measurement mode to the negative ion measurement mode.

(15) In FIG. 2, the analysis controller 50 is responsible for the general control of the entire system. The voltage controller 52 operates under the control of the analysis controller 50 to control the voltage sources for generating voltages to be applied to the relevant sections. The present system includes a considerable number of voltage sources, of which FIG. 2 shows only the first plate electrode voltage source 53, second plate electrode voltage source 54 and third plate electrode voltage source 55 which respectively apply predetermined voltages to the plate electrodes 171-173 included in the lens electrode 17. An input unit 51 for user operation is connected to the analysis controller 50. The input unit 51 includes a switch-waiting time setter 511 configured to allow users to set the switch-waiting time, which is one of the analysis conditions.

(16) In order to converge ions which have passed through the quadrupole mass filter 16 into the ion entrance opening 191a of the collision cell 19 and make the ions efficiently pass through, predetermined ion-converging DC voltages are applied to the three plate electrodes 171-173 in the lens electrode 17, respectively. Furthermore, a DC offset voltage having a voltage value corresponding to the amount of collision energy to be imparted to the ion entering the collision cell 19 (precursor ion) is additionally applied to the three plate electrodes 171-173.

(17) As one example, consider the case where the DC bias voltage applied to the ion guide 18 within the collision cell 19 is 0 V, and the DC offset voltage is ±200V. If the measurement mode is the positive ion measurement mode, the voltage controller 52 controls the first through third plate electrode voltage sources 53-55 so as to apply a DC offset voltage of +200V to each of the plate electrodes 171-173 forming the lens electrode 17. As a result, an electric field is created which imparts a predetermined amount of collision energy to a positive ion passing through the quadrupole mass filter 16 to introduce the ion into the collision cell 19.

(18) When a command to switch the measurement mode from the positive ion measurement mode to the negative ion measurement mode is sent from the analysis controller 50 to the voltage controller 52, the voltage controller 52 initially controls the first through third plate electrode voltage sources 53-55 so that the DC offset voltage applied to the plate electrodes 171-173 forming the lens electrode 17 is temporarily switched from +200V to 0V (Step S1). As a result, the DC offset voltage applied to the plate electrodes 171-173 changes from +200V to 0V, as indicated by the thick line in FIG. 4.

(19) The voltage controller 52 subsequently maintains the previously described state until the waiting time previously set by an internal timer is elapsed (Step S2). The waiting time is a period of time which is previously set by the user through the switch-waiting time setter 511 or specified by default. For example, this value is hereinafter assumed to be 2 msec. After the lapse of the waiting time (“Yes” in Step S2), the voltage controller 52 controls the first through third plate electrode voltage sources 53-55 so that the DC offset voltage applied to the plate electrodes 171-173 is switched to −200V which corresponds to the negative ion measurement mode (Step S3). By such an operation, the DC offset voltage applied to the plate electrodes 171-173 is maintained at 0V for 2 msec and then changes from 0V to −200V, as indicated by the thick line in FIG. 4.

(20) The switching operation from the negative ion measurement mode to the positive ion measurement mode is also performed in a similar manner: The DC offset voltage applied to the plate electrodes 171-173 is temporarily switched from −200V to 0V. After being maintained at 0V for 2 msec, the voltage is switched from 0V to +200V. Thus, in the Q-TOF mass spectrometer according to the present embodiment, when the measurement mode is switched between the positive and negative ion measurement modes, the DC offset voltage is temporarily switched to 0V and maintained at 0V for the previously set waiting time before the voltage is ultimately switched to the DC offset voltage corresponding to the measurement mode to be used after the switching operation.

(21) The voltage controller 52 sends a signal to the first through third plate electrode voltage sources 53-55 to simultaneously switch the voltage. However, a discrepancy may occur in the timing of the change in the voltage actually applied from the voltage sources 53-55 to the plate electrodes 171-173. This timing discrepancy mainly results from such factors as the variation in characteristics of the elements forming the circuits in the voltage sources or the difference in the amount of delay of the signals due to a difference in wiring length. The user should set a waiting time that is longer than the expected timing discrepancy.

(22) The waveform shown by the broken line in FIG. 4 is a waveform in the case where there is approximately 1.5 msec of timing discrepancy. If this timing discrepancy does not exceed the waiting time, there is no possibility that the DC offset voltage applied to one plate electrode is changed to −200V while the DC offset voltage applied to another plate electrode is still at +200V. That is to say, the voltage difference between the neighboring plate electrodes is limited to 200V and cannot be 400V. By restricting the voltage difference which occurs between the neighboring plate electrodes in this manner, the electric discharge between those electrodes can be prevented.

(23) Although the description so far has been concerned with only the voltages applied to the plate electrodes 171-173 forming the lens electrode 17, the same description is similarly applicable in the case of applying a DC offset voltage to the plate electrodes forming the ion guide 12 which is a Q array, for example.

(24) If the collision energy is considerably low, the DC offset voltage also becomes low. If the DC offset voltage is lowered to a certain extent, no electric discharge will occur even if a voltage difference which equals two times the DC offset voltage occurs between the neighboring electrodes. Accordingly, when the DC offset voltage is equal to or less than a predetermined value, the processing as shown in FIG. 3 may be omitted, and the polarity of the DC offset voltage may be immediately switched. This shortens the period of time for the switching operation between the positive and negative ion measurement modes.

(25) The previously described embodiment is concerned with the case of applying the present invention in a Q-TOF mass spectrometer. Understandably, the present invention is also applicable in a triple quadrupole mass spectrometer.

(26) Furthermore, it is evident that the previously described embodiment is a mere example of the present invention, and any change, modification, addition or the like appropriately made within the spirit of the present invention will fall within the scope of claims of the present application.

REFERENCE SIGNS LIST

(27) 1 . . . Chamber 2 . . . Ionization Chamber 3 . . . First Intermediate Vacuum Chamber 4 . . . Second Intermediate Vacuum Chamber 5 . . . Third Intermediate Vacuum Chamber 6 . . . First Analysis Chamber 7 . . . Second Analysis Chamber 10 . . . ESI Spray 11 . . . Heated Capillary 12 . . . Ion Guide 13 . . . Skimmer 14 . . . Ion Guide 16 . . . Quadrupole Mass Filter 17 . . . Lens Electrode 171, 172, 173 . . . Plate Electrode 18 . . . Ion Guide 19 . . . Collision Cell 20 . . . Ion Transport Optical System 30 . . . Flight Space 31 . . . Orthogonal Accelerator Section 32 . . . Reflector 33 . . . Back Plate 34 . . . Ion Detector 40 . . . Data Processing Unit 50 . . . Analysis Controller 51 . . . Input Unit 511 . . . Switch-Waiting Time Setter 52 . . . Voltage Controller 53 . . . First Plate Electrode Voltage Source 5 54 . . . Second Plate Electrode Voltage Source 55 . . . Third Plate Electrode Voltage Source