MASS SPECTROMETER

Abstract

When a Q-TOF type mass spectrometer is operated in an MS.sup.1 mode, a controller (40), at the time of measurement, controls voltage generators (31 to 33) such that only a V voltage (radio-frequency voltage for mass separation) and a direct-current bias voltage are applied to main rod electrodes of a quadrupole mass filter (12) without application of a U voltage (direct-current voltage for mass separation). During a measurement preparation period between a plurality of measurements to obtain one mass spectrum, the controller (40) controls a U voltage generator (31) so as to apply the U voltage to the main rod electrodes of the quadrupole mass filter (12). Accordingly, a direct-current electric field is formed between adjacent main rod electrodes around an ion optical axis (C) due to a potential difference, and electric charges accumulated in rod holders (122) holding the main rod electrodes are rapidly removed by an effect of this electric field. As a result, it is possible to eliminate a charge-up that has not been eliminated by a conventional method in which a polarity of a direct-current bias voltage applied to the rod electrodes is merely reversed.

Claims

1. A mass spectrometer having one or more ion transport optical elements each of which includes a plurality of electrodes arranged so as to surround an ion optical axis between an ion source that generates ions derived from a sample component and a detector which detects ions separated according to a mass-to-charge ratio, and transports ions while converging the ions by an effect of a radio-frequency electric field formed by the plurality of electrodes, the mass spectrometer comprising: a) a direct-current voltage generator configured to apply direct-current voltages of different polarities to electrodes adjacent to each other around the ion optical axis included in at least one of the one or more ion transport optical elements; and b) a controller configured to control an operation of the direct-current voltage generator so as to apply a predetermined direct-current voltage to each of the plurality of electrodes included in the at least one of the one or more ion transport optical elements from the direct-current voltage generator during a measurement preparation period during which no measurement is substantially performed between one measurement and a next measurement, and stop application of the direct-current voltage during a measurement period during which a measurement is performed.

2. The mass spectrometer according to claim 1, wherein the one or more ion transport optical elements include a quadrupole mass filter in a driving state in which a mass separation operation is not performed, and the direct-current voltage generator applies a direct-current voltage for ion separation to a plurality of rod electrodes included in the quadrupole mass filter.

3. The mass spectrometer according to claim 2, wherein the quadrupole mass filter is provided in front of a collision cell which dissociates ions, and a time-to-flight type mass separator which separates ions according to a mass-to-charge ratio is provided between the collision cell and the detector, and in a normal mass spectrometry mode in which the time-to-flight type mass spectrometer in a rear stage separates ions while the quadrupole mass filter does not separate ions, the controller is configured to control an operation of the direct-current voltage generator so as to apply a predetermined direct-current voltage to each of the plurality of electrodes included in the quadrupole mass filter during a period during which no measurement is substantially performed, and stop application of the direct-current voltage during a measurement period.

4. The mass spectrometer according to claim 3, wherein in the normal mass spectrometry mode, a measurement is repeated a predetermined number of times, and data obtained by each of the predetermined number of measurements are accumulated to create a mass spectrum in a predetermined mass-to-charge ratio range, and the controller is configured to control an operation of the direct-current voltage generator so as to apply a predetermined direct-current voltage to each of the plurality of electrodes included in the quadrupole mass filter from the direct-current voltage generator during the measurement preparation period between the predetermined number of measurements for obtaining one mass spectrum and the predetermined number of measurements for obtaining another mass spectrums, and stop application of the direct-current voltage during a measurement period.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0022] FIG. 1 is a schematic configuration diagram of a Q-TOF type mass spectrometer, which is an embodiment of the present invention.

[0023] FIG. 2 is a schematic configuration diagram of a quadrupole mass filter and its control system in the Q-TOF type mass spectrometer of the present embodiment.

[0024] FIG. 3 is a cross-sectional view of a quadrupole mass filter in a plane orthogonal to an ion optical axis.

[0025] FIG. 4 is a timing diagram in one analysis cycle.

DESCRIPTION OF EMBODIMENTS

[0026] A Q-TOF type mass spectrometer, which is an embodiment of the present invention, will be described with reference to the accompanying drawings.

[0027] FIG. 1 is a schematic configuration diagram of the Q-TOF type mass spectrometer of the present embodiment, FIG. 2 is a schematic configuration diagram of a quadrupole mass filter and its control system in FIG. 1, and FIG. 3 is a cross-sectional view of the quadrupole mass filter in a plane orthogonal to an ion optical axis.

[0028] The Q-TOF type mass spectrometer of the present embodiment has a configuration of a multi-stage differential evacuation system, and a chamber 1 is provided with an ionization chamber 2 having a substantially atmospheric pressure atmosphere and a second analysis chamber 6 with a highest degree of vacuum, a first intermediate vacuum chamber 3, a second intermediate vacuum chamber 4, and a first analysis chamber 5 in which the degree of vacuum increases in order from the ionization chamber 2 to the second analysis chamber 6.

[0029] The ionization chamber 2 is provided with an electrospray ionization (ESI) spray 7 for performing ionization by an ESI method, and when a liquid sample containing a target compound is supplied to the ESI spray 7, charged droplets are nebulized from a tip of the spray 7, ions derived from the target compound are generated in a process in which the charged droplets are divided and a solvent is evaporated. The ionization method is not limited to this, and other ionization methods such as an atmospheric pressure chemical ionization (APCI) method and an atmospheric pressure photoionization (APPI) method may be used.

[0030] Various ions generated in the ionization chamber 2 are sent to the first intermediate vacuum chamber 3 through a heating capillary 8, converged by an array type ion guide 9 arranged in the first intermediate vacuum chamber 3, and sent to the second intermediate vacuum chamber 4 through a skimmer 10. Further, the ions are converged by a multipole ion guide 11 arranged in the second intermediate vacuum chamber 4 and sent to the first analysis chamber 5. In the first analysis chamber 5, a quadrupole mass filter 12 and a collision cell 13 in which a multipole type ion guide 14 is arranged are provided.

[0031] Various ions derived from a sample are introduced into the quadrupole mass filter 12, and during an MS/MS analysis, ions having a specific mass-to-charge ratio according to a voltage applied to the quadrupole mass filter 12 pass through the quadrupole mass filter 12. These ions are introduced into the collision cell 13 as precursor ions, and the precursor ions are dissociated by contact with collision gas supplied into the collision cell 13 to generate various product ions. On the other hand, during normal mass spectrometry (MS.sup.1 analysis) without ion dissociation, the ions derived from a sample component pass through the quadrupole mass filter 12 almost as they are, are introduced into the collision cell 13, and supplied into the collision cell 13, and contact with the collision gas reduces (that is, cools) energy.

[0032] The ions derived from the sample component (product ions generated by dissociation or undissociated ions) are transported while being converged in the collision cell 13. Then, the ions discharged from the collision cell 13 are introduced into the second analysis chamber 6 through an ion passage port 15 while being guided by an ion transport optical system 16. In the second analysis chamber 6, an orthogonal accelerator 17 which is an ion ejection unit, a flight space 18 in which a reflector 19 is arranged, and an ion detector 20 are provided. The ions introduced into the orthogonal accelerator 17 in an X-axis direction along an ion optical axis C are ejected from the orthogonal accelerator 17 by being accelerated in a Z-axis direction in a pulsed manner at a predetermined timing. As shown by alternate long and two short dashes lines in FIG. 1, the ejected ions fly freely in the flight space 18, then are turned back by a reflected electric field formed by the reflector 19, fly freely in the flight space 18 again, and reach the ion detector 20.

[0033] A flight time from departure of the ions from the orthogonal accelerator 17 to arrival at the ion detector 20 depends on the mass-to-charge ratio of the ions. The ion detector 20 outputs an ion-intensity signal according to the amount of incident ions moment by moment. A data processor 21 receives the ion-intensity signal from the ion detector 20 and accumulates flight time spectrum data obtained by digitizing the signal, and then integrates the flight time spectrum data obtained by each of a plurality of measurements to create a flight time spectrum and converts the flight time into a mass-to-charge ratio to create a mass spectrum. The “measurement” described here refers to a cycle of acquiring an ion-intensity signal over a predetermined flight time range corresponding to one ion ejection.

[0034] As shown in FIG. 2, the quadrupole mass filter 12 includes a main quadrupole mass filter section 12B including four main rod electrodes (reference numerals 12B1 to 12B4 in FIG. 3) that substantially contribute to ion separation, and a pre-quadrupole mass filter section 12A including four short pre-rod electrodes located in front of the four main rod electrodes, respectively. The four main rod electrodes 12B1 to 12B4 are connected to the pre-rod electrodes in front of the four main rod electrodes 12B1 to 12B4, respectively, by a connecting rod 121 made of ceramic (or other non-conductive material). Further, the four main rod electrodes 12B1 to 12B4 are held by two annular rod holders 122 made of ceramic (or other non-conductive material). That is, the rod holders 122 hold the four main rod electrodes 12B1 to 12B4 at predetermined positions around the ion optical axis C with high accuracy, and the connecting rod 121 holds the pre-rod electrodes in front of the main rod electrodes 12B1 to 12B4 with high accuracy.

[0035] A quadrupole voltage generator 30 applies a predetermined voltage to each of the main rod electrodes 12B1 to 12B4 and pre-rod electrodes included in the quadrupole mass filter 12. The quadrupole voltage generator 30 includes a U voltage generator 31, a V voltage generator 32, a direct-current bias voltage generator 33, and first to third voltage addition units 34 to 36. A controller 40 controls operations of the U voltage generator 31, the V voltage generator 32, and the direct-current bias voltage generator 33.

[0036] A U voltage is a direct-current voltage for ion separation according to the mass-to-charge ratio, and the U voltage generator 31 generates a positive/negative direct-current voltage (±U), which is a predetermined voltage value, based on an instruction of the controller 40. A V voltage is a radio-frequency voltage for ion separation according to the mass-to-charge ratio, and the V voltage generator 32 generates radio-frequency voltages (±V cos ωt) of mutually reverse polarities, which are predetermined amplitude values, based on the instruction of the controller 40. The direct-current bias voltage generator 33 generates a predetermined direct-current bias voltage (VB) based on the instruction of the controller 40. Although this direct-current bias voltage does not contribute to the separation of ions, the ions can be accelerated or decelerated through utilization of a direct-current voltage difference from the ion guide 11 in a front stage.

[0037] When ions having a predetermined mass-to-charge ratio is allowed to pass through the quadrupole mass filter 12, the U voltage generator 31, the V voltage generator 32, and the direct-current bias voltage generator 33 each generate a predetermined voltage. The generated voltage added (superimposed) by the voltage addition units 34 and 35, which is a voltage+(U+V cos ωt)+Vb or −(U+V cos ωt+Vb, is applied to the main rod electrodes 12B1 to 12B. On the other hand, a voltage to which the U voltage is not added, which is a voltage+V cos ωt+Vb or −V cos ωt+Vb, is applied to the pre-rod electrode. The voltage value of U voltage and the amplitude value of V voltage are values according to the mass-to-charge ratio of the selected ions.

[0038] A radio-frequency electric field formed by the radio-frequency voltage applied to the pre-rod electrode constituting the pre-quadrupole mass filter section 12A mainly corrects an edge electric field due to the main rod electrodes 12B1 to 12B4, and helps favorable introduction of ions into a space surrounded by the main rod electrodes 12B1 to 12B4. The introduced ions vibrate due to a quadrupole electric field when passing through the space surrounded by the main rod electrodes 12B1 to 12B4, and only ions having a predetermined mass-to-charge ratio stably pass through the space and other ions are diverged on the way. In this way, the ions selected according to the mass-to-charge ratio pass through the quadrupole mass filter 12 and are sent to the rear stage.

[0039] As a matter of course, a predetermined voltage is applied to each component other than the quadrupole mass filter 12 such as the ESI spray 7 and the ion guide 9 in FIG. 1. However, since the component to which the predetermined voltage is applied is not important in the present invention, the description is omitted.

[0040] In the Q-TOF type mass spectrometer of the present embodiment, it is possible to perform an MS/MS analysis by dissociating the ions in the collision cell 13, but as described above, it is also possible to perform an MS.sup.1 analysis in which the ions are not dissociated in the collision cell 13. In the Q-TOF type mass spectrometer of the present embodiment, characteristic control is performed when a normal MS.sup.1 analysis is performed.

[0041] Hereinafter, the characteristic control operation will be described with reference to FIG. 4 in addition to FIGS. 1 to 3. FIG. 4 is a timing diagram during one analysis cycle in an MS.sup.1 mode.

[0042] In the MS.sup.1 mode, as shown in FIG. 4, n measurements (a plurality n of measurements) are repeated during one analysis cycle, and the flight time spectrum data obtained by each of the n measurements is integrated. The mass spectrum is obtained from the flight time spectrum obtained by the integration of the flight time spectrum data. In the MS.sup.1 mode, since ion separation is not performed by the quadrupole mass filter 12, no U voltage is applied to the main rod electrodes 12B1 to 12B4, and the V voltage is set to such a voltage that the ions in a predetermined mass-to-charge ratio range can be transported while being converged. Therefore, during the measurement in the MS.sup.1 analysis mode, a voltage+V cos ωt+Vb or −V cos ωt+Vb is applied to the main rod electrodes 12B1 to 12B. If the measurement conditions in n measurements during one analysis cycle, specifically the mass-to-charge ratio range of ions passing through the quadrupole mass filter 12 and ion guides 9, 11 and 14, are the same, a mass spectrum with high sensitivity can be obtained.

[0043] In addition, the mass-to-charge ratio range of ions that can pass through the ion guides 9, 11, 14 or the quadrupole mass filter 12 driven so as to allow passing of the ions is usually limited. In particular, the mass-to-charge ratio range becomes relatively narrow when passing of ions with a low mass-to-charge ratio is allowed. Therefore, in n measurements during one analysis cycle, the mass-to-charge ratio range of the ions that pass through the quadrupole mass filter 12 and the ion guides 9, 11 and 14 is changed so as to obtain a mass spectrum over a wider mass-to-charge ratio range.

[0044] As described above, no U voltage is applied to the four main rod electrodes 12B1 to 12B4 of the quadrupole mass filter 12 during n measurements during one analysis cycle in the MS.sup.1 analysis mode. On the other hand, a measurement preparation period of a predetermined time is provided between the n measurements in one analysis cycle and the n measurements in the next analysis cycle. Then, the controller 40 operates the U voltage generator 31 only during the predetermined time during the measurement preparation period, and applies a U voltage to each of the four main rod electrodes 12B1 to 12B4. What is important is to apply direct-current voltages of different polarities to the main rod electrodes 12B1 to 12B4 adjacent to each other around the ion optical axis C. Therefore, the voltage value of the U voltage applied at this time may correspond to any of the mass-to-charge ratios of the ions passing through the main quadrupole mass filter section 12B.

[0045] When U voltages of different polarities are applied to the adjacent main rod electrodes 12B1 to 12B4 around the ion optical axis C, a large direct-current electric field is formed between two adjacent main rod electrodes, for example, the main rod electrodes 12B1 and 12B4, or the main rod electrodes 12B1 and 12B2 in FIG. 3. Electric charges accumulated in the portion between the adjacent main rod electrodes 12B1 to 12B4 in the rod holders 122 rapidly move in a direction of one of the main rod electrode 12B1 to 12B4 by an effect of this electric field and disappear. As a result, a charge-up of the rod holders 122 is eliminated. During this charge-up elimination operation, it is preferable to stop applying the V voltage to the main rod electrodes 12B1 to 12B4 so as not to hinder a smooth movement of the accumulated electric charges.

[0046] For the time during which the U voltages are applied during the measurement preparation period, it is desirable to consider and decide in advance time required for the potentials of the main rod electrodes 12B1 to 12B4 to settle to the potentials in the next measurement after the application of the U voltages is stopped. Specifically, for example, when the measurement preparation period is 1 msec, the U voltages are applied to the four main rod electrodes 12B1 to 12B4 only during the first 200 μsec of the measurement preparation period, and when 200 μsec elapses, the voltages may be switched to voltages to be applied to the main rod electrodes 12B1 to 12B4 in the next measurement.

[0047] In the above embodiment, the charge-up elimination operation is performed by applying the U voltage once in one analysis cycle, but it is not always necessary to perform the charge-up elimination operation in each analysis cycle. For example, the charge-up elimination operation may be performed in every predetermined number of analysis cycles.

[0048] Further, in the above embodiment, the electric charges accumulated in the rod holders holding the rod electrodes of the quadrupole mass filter in the Q-TOF type mass spectrometer are removed. The present invention is also effective in removing electric charges accumulated in a structure such as rod holders holding the rod electrodes constituting the ion guides that converge and transport ions by an effect of the radio-frequency electric field. However, since such ion guides generally do not have a circuit corresponding to the above-mentioned U voltage generator 31, it is necessary to specially add such a circuit.

[0049] Further, it is clear that the present invention can be applied not only to the Q-TOF type mass spectrometer but also to a triple quadrupole mass spectrometer and a single type quadrupole mass spectrometer.

[0050] Furthermore, since all of the above embodiments are examples of the present invention, it is clear that points other than those described above are included in the claims of the present application even if they are appropriately modified, added, or corrected within the scope of the present invention.

REFERENCE SIGNS LIST

[0051] 1 . . . Chamber [0052] 2 . . . Ionization Room [0053] 3 . . . First Intermediate Vacuum Chamber [0054] 4 . . . Second Intermediate Vacuum Chamber [0055] 5 . . . First Analysis Room [0056] 6 . . . Second Analysis Room [0057] 7 . . . ESI Spray [0058] 8 . . . Heating Capillary [0059] 9 . . . Array Type Ion Guide [0060] 10 . . . Skimmer [0061] 11 . . . Multipole Ion Guide [0062] 12 . . . Quadrupole Mass Filter [0063] 12A . . . Pre-Quadrupole Mass Filter Section [0064] 12B . . . Main Quadrupole Mass Filter Section [0065] 12B1-12B4 . . . Main Rod Electrode [0066] 121 . . . Connecting Rod [0067] 122 . . . Rod Holder [0068] 13 . . . Collision cell [0069] 14 . . . Ion Guide [0070] 15 . . . Ion Passage Port [0071] 16 . . . Ion Transport Optical System [0072] 17 . . . Orthogonal Accelerator [0073] 18 . . . Flight Space [0074] 19 . . . Reflector [0075] 20 . . . Ion Detector [0076] 21 . . . Data Processor [0077] 30 . . . Quadrupole Voltage Generator [0078] 31 . . . U Voltage Generator [0079] 32 . . . V Voltage Generator [0080] 33 . . . Direct-Current Bias Voltage Generator [0081] 34 . . . Voltage Addition Unit [0082] 40 . . . Controller [0083] C . . . Ion Optical Axis