Time-of-flight mass spectrometer

Abstract

To acquire a mass spectrum for a wide mass range, a normal analysis execution controlling unit controls components to repeatedly perform measurement while changing setting m/z by a predetermined m/z at a time, and a mass spectrum summarizing processing unit summarizes data pieces each obtained by each time of measurement to generate the mass spectrum. Radio-frequency voltage applied to an ion guide and the like is changed based on the setting m/z. The radio-frequency voltage for the setting m/z is determined using a table in which a relationship between a position on an axis between upper and lower limits of the mass range and the radio-frequency voltage is substantially the same regardless of the mass range.

Claims

1. A time-of-flight mass spectrometer including an ion source for ionizing a sample component, a time-of-flight mass spectrometry unit including an ion ejecting unit for ejecting ions generated by the ion source or other ions derived from the generated ions into a flight space, and one or a plurality of ion transport optical elements for transporting the ions while focusing the ions by means of a radio-frequency electric field, the one or plurality of ion transport optical elements being provided between the ion source and the ion ejecting unit, the time-of-flight mass spectrometer comprising: a) a voltage generating unit for applying radio-frequency voltage for forming the radio-frequency electric field to each of the one or plurality of ion transport optical elements; b) a controlling unit for determining, in response to a mass range designated as an observation target, a radio-frequency voltage applied to each of the one or plurality of ion transport optical elements in each of a plurality of times of measurement using different measurement target mass-to-charge ratio ranges for acquiring a mass spectrum entirely covering a mass-to-charge ratio range of the mass range, and for controlling components to perform the plurality of times of measurement while changing the radio-frequency voltage applied to each of the one or plurality of ion transport optical elements by the voltage generating unit, the controlling unit determining the radio-frequency voltage for each of the plurality of times of measurement to maintain a ratio of times of measurement in which radio-frequency voltage is set so that ion passage efficiency in a low mass-to-charge ratio region is relatively high among the plurality of times of measurement to be substantially constant regardless of a width of the mass range; and c) a mass spectrum summarizing processing unit for obtaining a mass spectrum corresponding to the mass range by summarizing mass spectrum data pieces obtained by the plurality of respective times of measurement under control by the controlling unit.

2. The time-of-flight mass spectrometer according to claim 1, wherein the controlling unit determines the radio-frequency voltage based on a table or a formula in which a relationship between a position on an axis between upper and lower limits of the mass range and the radio-frequency voltage is substantially same between different mass ranges.

3. The time-of-flight mass spectrometer according to claim 2, wherein a quadrupole mass filter capable of selectively allowing ions with a certain mass-to-charge ratio to pass through and a collision cell for dissociating the ions are provided between the ion source and the ion ejecting unit, and the quadrupole mass filter operating without selecting the ions and an ion guide provided in the collision cell collectively serve as one of the one or plurality of ion transport optical elements.

4. The time-of-flight mass spectrometer according to claim 1, wherein a quadrupole mass filter capable of selectively allowing ions with a certain mass-to-charge ratio to pass through and a collision cell for dissociating the ions are provided between the ion source and the ion ejecting unit, and the quadrupole mass filter operating without selecting the ions and an ion guide provided in the collision cell collectively serve as one of the one or plurality of ion transport optical elements.

5. The time-of-flight mass spectrometer according to claim 4, wherein one or a plurality of ion guides provided between the ion source and the quadrupole mass filter serve as the one or plurality of ion transport optical elements.

Description

BRIEF DESCRIPTION OF DRAWINGS

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

(2) FIGS. 2A-2B are diagrams illustrating an example of a radio-frequency voltage scanning table used in the Q-TOF mass spectrometer according to the present embodiment.

(3) FIG. 3 is a schematic view illustrating a relationship between setting m/z and a radio-frequency voltage parameter in the Q-TOF mass spectrometer according to the present embodiment.

(4) FIGS. 4A-4B are diagrams illustrating an example of a radio-frequency voltage scanning table used in a conventional Q-TOF mass spectrometer.

(5) FIG. 5 is a schematic view illustrating a relationship between setting m/z and a radio-frequency voltage parameter in the conventional Q-TOF mass spectrometer.

(6) FIG. 6 is a schematic diagram illustrating normalized values of the intensities of measurement target ions with the respective mass-to-charge ratios of m/z 200, m/z 500, and m/z 800 for passing through an ion guide, relative to the setting m/z.

(7) FIGS. 7A-7B illustrate relationship between a mass spectrum obtained by each time of measurement and a summarized mass spectrum, in a case where a mass spectrum is obtained with a mass range of m/z 10 to 600 and a case where a mass spectrum is obtained with a wider mass range of m/z 10 to 2000.

DESCRIPTION OF EMBODIMENTS

(8) A Q-TOF mass spectrometer, which is an embodiment of the present invention will be described with reference to the accompanying drawings.

(9) FIG. 1 is a configuration diagram of a main part of the Q-TOF mass spectrometer of the present embodiment.

(10) The Q-TOF mass spectrometer of the present embodiment has a configuration of a multi-stage differential evacuation system with a chamber 1 containing an ionization chamber 2 at a substantially atmospheric atmosphere and a second analysis chamber 6 with the highest degree of vacuum, as well as a first intermediate vacuum chamber 3, a second intermediate vacuum chamber 4, and a first analysis chamber 5 with their degree of vacuum increasing in this order from the ionization chamber 2 to the second analysis chamber 6.

(11) The ionization chamber 2 is provided with an electrospray ionization (ESI) spray 7 for performing ionization by ESI. When a sample solution including a target compound is supplied to the ESI spray 7, it is nebulized in charged droplets from the distal end of the spray 7. As the charged droplets split and the solvent evaporates, ions derived from the target compound are generated. The ionization is not limited to this, and other types of ionization such as atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) may be employed.

(12) The various ions generated in the ionization chamber 2 are sent to the first intermediate vacuum chamber 3 through a heating capillary 8, focused by an array type ion guide 9 provided in the first intermediate vacuum chamber 3, and are sent to the second intermediate vacuum chamber 4 through a skimmer 10. The ions are further focused by a multipole type ion guide 11 provided in the second intermediate vacuum chamber 4, and are then sent to the first analysis chamber 5. The first analysis chamber 5 contains a quadrupole mass filter 12 and a collision cell 13 incorporating an ion guide 14 of a multipole type.

(13) The various ions derived from the sample are introduced into the quadrupole mass filter 12. When MS/MS analysis is performed, ions having a certain mass-to-charge ratio corresponding to the voltage applied to the quadrupole mass filter 12 pass through the quadrupole mass filter 12. The ions are introduced into the collision cell 13 as precursor ions. The precursor ions are dissociated by coming into contact with the collision gas supplied into the collision cell 13. Thus, various product ions are generated. On the other hand, at the time of normal mass spectrometry (MS.sup.1 analysis) not involving the ion dissociation, the ions derived from the sample component pass through the quadrupole mass filter 12 almost intact (still, the mass-to-charge ratio range enabling the passage is actually limited as described later) to be introduced into the collision cell 13. Then, the ions come into contact with the collision gas supplied into the collision cell 13 so that their energy is reduced (i.e. cooled).

(14) In the collision cell 13, the ions derived from the sample components are transported while being focused. The ions ejected 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. The second analysis chamber 6 contains an orthogonal acceleration unit 17 serving as an ion ejection portion, a flight space 18 provided with a reflector 19, and an ion detector 20. The ions introduced into the orthogonal acceleration unit 17 in the X axis direction along an ion optical axis C are accelerated in the Z axis direction at a predetermined timing to be ejected. The ejected ions fly freely in the flight space 18 as indicated by the two-dot chain line in FIG. 1, reflected by a reflecting electric field formed by the reflector 19 to fly freely again in the flight space 18, and reach the ion detector 20. The time of flight of the ions between the departure from the orthogonal acceleration unit 17 and the arrival at the ion detector 20 depends on the mass-to-charge ratio of the ions.

(15) A data processing unit 30 includes functional blocks of a data collection unit 31 and a mass spectrum summarizing processing unit 32. The data collection unit 31 receives detection signal from the ion detector 20 and digitizes and accumulates the signal. The mass spectrum summarizing processing unit 32 generates a time-of-flight spectrum based on the collected data, and converts the time of flight into a mass-to-charge ratio to generate a mass spectrum. The mass spectrum summarizing processing unit 32 summarizes partial mass spectra each obtained by one of a plurality of times of measurement, as described later, to generate a mass spectrum of a wider mass-to-charge ratio range.

(16) First to fourth voltage generating units 21 to 24 apply predetermined radio-frequency voltage respectively to the array type ion guide 9, the multipole type ion guide 11, the quadrupole mass filter 12, and the ion guide 14. Furthermore, appropriate DC voltages are also applied to components including these electrodes, but the description of a voltage generating unit for generating such voltages is omitted. Furthermore, predetermined DC voltages are applied other components (such as, for example, the heating capillary 8 and the skimmer 10) but the description of the other components is omitted. Thus, in this document, a description is given only on the components for applying the radio-frequency voltage to ion optical elements having the function of transporting ions while focusing them by means of a radio-frequency electric field, related to the characteristic operation of the apparatus of the present embodiment.

(17) The first to the fourth voltage generating units 21 to 24 are each controlled by an analysis controlling unit 40. Functional blocks of the analysis controlling unit 40 include a normal analysis execution controlling unit 41 and a radio-frequency voltage scanning table storage unit 42. An input unit 44 receives an operation by the user, and a main controlling unit 43 is in charge of overall control of a user interface and the apparatus as a whole.

(18) The analysis controlling unit 40, the main controlling unit 43, and the data processing unit 30 are entirely or partially implemented with a personal computer, which is a physical entity, executing dedicated control/processing software installed in the computer.

(19) In the Q-TOF mass spectrometer of the present embodiment, the MS/MS analysis can be performed by dissociating the ions in the collision cell 13. Furthermore, as described above, the MS.sup.1 analysis without the dissociation of the ions in the collision cell 13 can also be performed. The Q-TOF mass spectrometer of the present embodiment performs characteristic control and processing when performing the normal MS.sup.1 analysis. Operations in the characteristic control and processing operations will be described below with reference to FIGS. 2 and 3.

(20) FIGS. 2A-2B are diagrams illustrating an example of a radio-frequency voltage scanning table in FIG. 1. FIG. 3 is a schematic view illustrating a relationship between the setting m/z and a radio-frequency voltage parameter in the Q-TOF mass spectrometer of the present embodiment. In addition, for the purpose of comparison with these FIGS. 2A-2B and FIG. 3, FIGS. 4A-4B and FIG. 5 are provided that respectively illustrate an example of a radio-frequency voltage scanning table used in a conventional Q-TOF mass spectrometer and illustrate a relationship between setting m/z and a radio-frequency voltage parameter in the conventional Q-TOF mass spectrometer.

(21) When the normal analysis is performed, the quadrupole mass filter 12 transports the ions to the subsequent stage while focusing the ions by means of a radio-frequency electric field. Thus, like the ion guides 9, 11 and 14, the quadrupole mass filter 12 substantially serves as an ion guide using a radio-frequency electric field. Therefore, the ions derived from the sample component generated by the ion source pass through the four ion guides (the array type ion guide 9, the multipole type ion guide 11, the quadrupole mass filter 12, and the ion guide 14) to be introduced into the orthogonal acceleration unit 17. Any ion guide that uses a radio-frequency electric field imposes a limit to the mass-to-charge ratio range of the ions passing through. For the sake of simplicity of explanation, the array type ion guide 9 and the multipole type ion guide 11 are collectively regarded as one ion guide A, the quadrupole mass filter 12 is regarded as an ion guide B, and the ion guide 14 is regarded as an ion guide C.

(22) Now, a case will be described where a summarized mass spectrum is acquired for two mass ranges with m/z 10 to 600 and with m/z 10 to 2000. As illustrated in FIGS. 4A-4B, in the radio-frequency voltage scanning table in the conventional apparatus, the radio-frequency parameter (a relative value of the parameter that determines the amplitude of the radio-frequency voltage) does not change depending on the mass range, as long as the setting m/z is the same. Therefore, as illustrated in FIG. 5, the relationship between the setting m/z and the radio-frequency parameter in the mass-to-charge ratio range of m/z 10 to 600 is exactly the same between the mass range m/z 10 to 2000 and the mass range m/z 10 to 600. Furthermore, the radio-frequency parameter is constant in a range m/z 600 to 2000 in the mass range m/z 10 to 2000.

(23) On the other hand, in the radio-frequency voltage scanning table in the Q-TOF mass spectrometer of the present embodiment, as illustrated in FIGS. 2A-2B, the entire mass-to-charge ratio range of each of the mass range m/z 10 to 600 and the mass range m/z 10 to 2000 is divided into six approximately equal sections. The mass-to-charge ratio at the boundaries among the six sections is defined as the setting m/z. The same radio-frequency parameter value is set for the setting m/z at the boundaries of the corresponding sections of different mass ranges. Specifically, for example, the same radio-frequency parameter value is set for the setting m/z 1000 in the mass range m/z 10 to 2000 and the setting m/z 300 in the mass range m/z 10 to 600. Therefore, as illustrated in FIG. 3, in both the mass range m/z 10 to 2000 and the mass range m/z 10 to 600, the relationship between the radio-frequency voltage and a position on an axis between the upper and lower limits of the mass range is substantially the same. In other words, a line graph indicating the relationship between the setting m/z and the radio-frequency parameter in the mass range m/z 10 to 2000 is of a shape obtained by directly extending, in a lateral direction (direction of an axis representing a mass-to-charge ratio), a line graph indicating the relationship between the setting m/z and the radio-frequency parameter in the mass range m/z 10 to 600.

(24) Before the normal mass spectrometry is implemented, the user designates the observation target mass range using the input unit 44. Although there are only two types of mass ranges in FIGS. 2 and 3, more types of mass ranges may be prepared beforehand. The normal analysis execution controlling unit 41 acquires the radio-frequency parameter table corresponding to the designated mass range(s) from the radio-frequency voltage scanning table storage unit 42, and determines the radio-frequency voltage applied to the ion guides A, B, and C based on the acquired table.

(25) Thus, the normal analysis execution controlling unit 41 sets the setting m/z to be increased by a predetermined mass-to-charge ratio (for example, m/z 50 at a time as in the example illustrated in FIGS. 7A-7B) within the mass-to-charge ratio range of the designated mass range, acquires the radio-frequency parameter value corresponding to the setting m/z from the radio-frequency parameter table, and controls the voltage generating units 21 to 24 to apply the radio-frequency voltage based on the acquired radio-frequency parameter value to the ion guides A, B, and C. Note that, as a general practice, the radio-frequency parameter value corresponding to the setting m/z not included in the radio-frequency parameter table may be obtained by a method such as linear interpolation.

(26) Ions derived from sample components are measured while the radio-frequency voltage corresponding to one setting m/z being applied to each of the ion guides A, B, and C, and the data collection unit 31 stores mass spectrum data obtained by the measurement. The normal analysis execution controlling unit 41 repeats the same measurement while changing the setting m/z step by step, that is, while changing the radio-frequency voltage applied to the ion guides A, B, and C. Then, measurement is performed for each of a plurality of settings m/z over the entire mass-to-charge ratio range of the mass range, and then the measurement is terminated.

(27) When the setting m/z is changed by m/z 50 at a time as illustrated in FIGS. 7A-7B, a change in the radio-frequency voltage in the case of the mass range m/z 10 to 2000 in the apparatus according to the present embodiment is moderate compared with a change in the radio-frequency voltage in the case of the mass range m/z 10 to 2000 in the conventional apparatus, as is clear from the comparison between FIG. 3 and FIG. 5. Therefore, with the apparatus according to the present embodiment, a large amount of mass spectrum data under a condition with a substantially high ion detection sensitivity is collected in the low mass-to-charge ratio region, when the mass range is wide. The mass spectrum summarizing processing unit 32 summarizes mass spectrum data pieces corresponding to a plurality of times of measurement obtained for the entire mass range, with the mass spectrum data pieces generally featuring a high ion intensity in the low mass-to-charge ratio region as described above. Thus, monitoring of the peak in the low mass-to-charge ratio region is facilitated with the mass spectrum as a result of the summarizing processing.

(28) As described above, with the Q-TOF mass spectrometer according to the present embodiment, a mass spectrum with sufficiently high sensitivity in the low mass-to-charge ratio region can be obtained even when the mass range is wide. Furthermore, the peak pattern corresponding to the same mass-to-charge ratio range is less likely to be different between cases where the mass range is wide and narrow. This facilitates comparison between mass spectra obtained with different mass ranges.

(29) It should be noted that the numerical values used in the above embodiment, such as the numerical values in the table illustrated in FIGS. 2A-2B and the relationship between the setting m/z and the radio-frequency parameter value, are merely examples.

(30) Further, the above described embodiment is about applying the present invention to the Q-TOF mass spectrometer capable of implementing MS/MS analysis. The present invention can also be applied to mass spectrometers such as an OA-TOFMS capable of implementing normal mass spectrometry only.

(31) The embodiments described above are examples of the present invention, and thus modification, correction, addition, and the like to the embodiments without departing from the gist of the present invention are apparently included in the scope of the claims of the present application.

REFERENCE SIGNS LIST

(32) 1 . . . Chamber 2 . . . Ionization Chamber 3 . . . First Intermediate Vacuum Chamber 4 . . . Second Intermediate Vacuum Chamber 5 . . . First Analysis Chamber 6 . . . Second Analysis Chamber 7 . . . ESI Spray 8 . . . Heating Capillary 9 . . . Array Type Ion Guide 10 . . . Skimmer 11 . . . Multipole Type Ion Guide 12 . . . Quadrupole Mass Filter 13 . . . Collision Cell 14 . . . Ion Guide 15 . . . Ion Passage Port 16 . . . Ion Transport Optical System 17 . . . Orthogonal Acceleration Unit 18 . . . Flight Space 19 . . . Reflector 20 . . . Ion Detector 30 . . . Data Processing Unit 31 . . . Data Collection Unit 32 . . . Mass Spectrum Summarizing Processing Unit 40 . . . Analysis Controlling Unit 41 . . . Normal Analysis Execution Controlling Unit 42 . . . Radio-frequency Voltage Scanning Table Storage Unit 43 . . . Main Controlling Unit 44 . . . Input Unit C . . . Ion Optical Axis