Time-of-flight mass spectrometer

Abstract

Ions ejected substantially simultaneously from a collision cell after being temporarily held inside the collision cell arrive at an orthogonal acceleration unit through an ion transport optical system. When the ions enter the orthogonal acceleration unit, voltages having a predetermined potential difference are applied to an entrance-side electrode and an exit-side auxiliary electrode, and as a result an electric field having a rising potential gradient along an axis is created in the orthogonal acceleration unit. As ions having low an m/z values and entering the orthogonal acceleration unit first is significantly decelerate, the packet of ions spread in the X-axis direction in accordance with the m/z values are compressed in the X-axis direction after entering the orthogonal acceleration unit. Thus, a mass-to-charge ratio range of ions that are accelerated in the orthogonal acceleration unit is broadened, and a mass spectrum of a broad range of mass-to-charge ratios can be obtained.

Claims

1. An orthogonal acceleration time-of-flight mass spectrometer including an orthogonal acceleration unit for accelerating incident ions in a direction orthogonal to an incident axis of the ions, and a separation-detection unit for separating and detecting accelerated ions in accordance with mass-to-charge ratios, comprising: a) an ion holding unit for temporarily holding ions that are a measurement object; b) an ion transport optical system, arranged between the ion holding unit and the orthogonal acceleration unit, for guiding ions that are ejected from the ion holding unit to the orthogonal acceleration unit; c) an ion travel adjusting unit for, at a time when ions enter the orthogonal acceleration unit from the ion transport optical system, creating an electric field having a rising potential gradient for the ions along an incident axis of the ions in a space of the orthogonal acceleration unit in which the ions are accelerated in an orthogonal direction; and d) a voltage application unit for, at a time of ejecting ions from the ion holding unit, applying a voltage to a constituent member included in each of the ion holding unit, the ion transport optical system and the orthogonal acceleration unit, so as to create an accelerating electric field that accelerates ions in a first region between an exit end of the ion holding unit and an entrance end of the ion transport optical system and to create, in a second region between an exit end of the ion transport optical system and an entrance end of the orthogonal acceleration unit, a decelerating electric field that decelerates ions and has a potential difference that is less than a potential difference in the first region.

2. The time-of-flight mass spectrometer according to claim 1, wherein: the ion travel adjusting unit creates the electric field having the rising potential gradient for ions along the incident axis of the ions by means of voltages applied to each of an electrode installed on an ion entrance side and an electrode installed at a frontward position in an ion travel direction along the incident axis in the orthogonal acceleration unit.

3. The time-of-flight mass spectrometer according to claim 1, wherein the ion holding unit is a linear ion trap that is disposed inside a collision cell for dissociating ions.

4. The time-of-flight mass spectrometer according to claim 1, wherein the ion holding unit, and the orthogonal acceleration unit and the separation-detection unit, are disposed in different vacuum chambers that are separated by a partition wall, and the ion transport optical system is disposed so as to straddle both vacuum chambers and sandwich an ion passage opening provided in the partition wall.

5. The time-of-flight mass spectrometer according to claim 2, wherein the ion holding unit is a linear ion trap that is disposed inside a collision cell for dissociating ions.

6. The time-of-flight mass spectrometer according to claim 2, wherein the ion holding unit, and the orthogonal acceleration unit and the separation-detection unit, are disposed in different vacuum chambers that are separated by a partition wall, and the ion transport optical system is disposed so as to straddle both vacuum chambers and sandwich an ion passage opening provided in the partition wall.

7. The time-of-flight mass spectrometer according to claim 3, wherein the ion holding unit, and the orthogonal acceleration unit and the separation-detection unit, are disposed in different vacuum chambers that are separated by a partition wall, and the ion transport optical system is disposed so as to straddle both vacuum chambers and sandwich an ion passage opening provided in the partition wall.

8. The time-of-flight mass spectrometer according to claim 5, wherein the ion holding unit, and the orthogonal acceleration unit and the separation-detection unit, are disposed in different vacuum chambers that are separated by a partition wall, and the ion transport optical system is disposed so as to straddle both vacuum chambers and sandwich an ion passage opening provided in the partition wall.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is an overall configuration diagram of an orthogonal acceleration TOFMS as one embodiment of the present invention.

(2) FIG. 2A, FIG. 2B and FIG. 2C are a detailed configuration diagram of a collision cell and an orthogonal acceleration unit shown in FIG. 1, a schematic potential distribution chart on an axis C, and a view illustrating the behavior of ions in a space between the collision cell and the orthogonal acceleration unit, respectively.

(3) FIG. 3A is a detailed configuration diagram of the orthogonal acceleration unit shown in FIG. 1, FIG. 3B is a schematic potential distribution chart on an axis C, and FIG. 3C and FIG. 3D are explanatory diagrams for describing the behavior of ions.

(4) FIG. 4 is a detailed configuration diagram of an orthogonal acceleration unit of an orthogonal acceleration TOFMS as another embodiment of the present invention.

(5) FIG. 5 is a detailed configuration diagram of an orthogonal acceleration unit of an orthogonal acceleration TOFMS as another embodiment of the present invention.

(6) FIG. 6A, FIG. 6B, and FIG. 6C are a detailed configuration diagram of a collision cell and an orthogonal acceleration unit in a conventional Q-TOFMS, a potential distribution chart on an axis C, and a timing chart of an applied voltage to an exit-side gate electrode and an orthogonal acceleration voltage, respectively.

DESCRIPTION OF EMBODIMENTS

(7) A Q-TOFMS as one embodiment of the present invention is hereinafter described with reference to the attached drawings.

(8) FIG. 1 is an overall configuration diagram of a Q-TOFMS of the present embodiment.

(9) The Q-TOFMS of the present embodiment has a configuration of a multistage differential pumping system, in which, inside a chamber 1, three (first to third) intermediate vacuum chambers 3, 4 and 5 are arranged between an ionization chamber 2 at approximately atmospheric atmosphere and a high vacuum chamber 6 in which the degree of vacuum is highest.

(10) An ESI spray 7 for performing electrospray ionization (ESI) is provided in the ionization chamber 2. When a sample solution containing a target compound is supplied to the ESI spray 7, biased electrical charges are imparted to the tip of the spray 7, and ions originating from the target compound are generated from sprayed droplets. The ionization method is not limited thereto and, for example, when the sample is a liquid, apart from ESI, an atmospheric pressure ionization method such as APCI or PESI can be used, when the sample is in a solid state, the MALDI method or the like can be used, and when the sample is in a gaseous state, the EI method or the like can be used.

(11) The various kinds of ions that are generated are sent to the first intermediate vacuum chamber 3 through a heating capillary 8, are focused by an ion guide 9 and then sent to the second intermediate vacuum chamber 4 through a skimmer 10. Furthermore, the ions are focused by an octopole ion guide 11 and sent to the third intermediate vacuum chamber 5. A quadrupole mass filter 12 and a collision cell 13 inside which a quadrupole-type ion guide 14 functioning as a linear ion trap is provided are disposed inside the third intermediate vacuum chamber 5. Various kinds of ions originating from the sample are introduced to the quadrupole mass filter 12, and only ions having a specific mass-to-charge ratio in accordance with 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 inside the collision cell 13 by contact with a CID gas supplied from outside, and various kinds of product ions are generated.

(12) The ion guide 14 functions as a linear ion trap, and the generated product ions are temporarily held therein. The ions that are being held are released from the collision cell 13 at a predetermined timing, and are introduced into the high vacuum chamber 6 through an ion passage opening 15 while being guided by an ion transport optical system 16. The ion transport optical system 16 is disposed straddling the third intermediate vacuum chamber 5 and the high vacuum chamber 6 in a condition in which the ion transport optical system 16 sandwiches the ion passage opening 15.

(13) An orthogonal acceleration unit 17 that is an ion ejection source, a flight space 20 including a reflector 21 and a back plate 22, and an ion detector 23 are provided inside the high vacuum chamber 6. Ions that are introduced in the X-axis direction into the orthogonal acceleration unit 17 are accelerated in the Z-axis direction at a predetermined timing and thus brought into flight. The ions first fly freely, thereafter turn back due to a reflecting electric field that is formed by the reflector 21 and the back plate 22, and again fly freely to arrive at the ion detector 23. A time of flight from a time point at which the ions depart from the orthogonal acceleration unit 17 until the ions arrive at the ion detector 23 depends on the mass-to-charge ratios of the respective ions. Accordingly, a data processing unit (not shown) which receives detection signals from the ion detector 23 calculates mass-to-charge ratios based on the times of flight of the respective ions, and for example, creates a mass spectrum.

(14) FIG. 2A shows a detailed configuration diagram of a space between the collision cell 13 and the orthogonal acceleration unit 17 shown in FIG. 1, FIG. 2B is a schematic potential distribution chart on an axis (in this case, an ion-optical axis) C, and FIG. 2C is a view illustrating the behavior of ions in the space between the collision cell 13 and the orthogonal acceleration unit 17. FIG. 3A is a detailed configuration diagram of the orthogonal acceleration unit shown in FIG. 1, FIG. 3B is a schematic potential distribution chart on an axis C, and FIG. 3C and FIG. 3D are explanatory diagrams for describing the behavior of ions in the orthogonal acceleration unit 17.

(15) As shown in FIG. 2A, a front end face and a rear end face of the collision cell 13 have an entrance-side gate electrode 131 and an exit-side gate electrode 132, respectively. The entrance-side gate electrode 131 and exit-side gate electrode 132 and the ion guide 14 function substantially as a linear ion trap. The ion transport optical system 16 has a structure in which a number of (in this example, eight) disc-like electrode plates that each have a circular aperture at the center are arranged along the axis C. The orthogonal acceleration unit 17 includes an annular entrance-side electrode 171, a tabular push-out electrode 172, a grid-like pull-out electrode 173, and an annular exit-side auxiliary electrode 174.

(16) Under control of a controlling unit 30, an exit-side gate electrode voltage generating unit 31 applies a predetermined voltage to the exit-side gate electrode 132, an ion transport optical system voltage generating unit 32 applies a predetermined voltage to each electrode plate included in the ion transport optical system 16, respectively, and an orthogonal acceleration unit voltage generating unit 33 applies a predetermined voltage to the entrance-side electrode 171, the push-out electrode 172, the pull-out electrode 173 and the exit-side auxiliary electrode 174, respectively.

(17) Only components that are necessary for describing characteristic operations are illustrated in FIG. 2, and although not illustrated in the drawings, appropriate voltages are also applied to the ion guide 14 and the entrance-side gate electrode 131 and the like.

(18) The alternate long and short dash line U1 shown in FIG. 2B represents a schematic potential distribution when ions are being held in the linear ion trap (inside the collision cell 13). At this time, the exit-side gate electrode voltage generating unit 31 applies a predetermined voltage to the exit-side gate electrode 132 that is higher than a predetermined voltage applied to the ion guide 14. By this means, as shown by the alternate long and short dash line U1 in FIG. 2B, the exit-side gate electrode 132 has a potential E2 that is higher than a potential E1 of the ion guide 14, and as a result ions are mainly held inside the ion guide 14. This situation is the same as in the case of the conventional apparatus that was described above using FIG. 6B.

(19) In this state, by application of a voltage from the orthogonal acceleration unit voltage generating unit 33 to the entrance-side electrode 171, the entrance-side electrode 171 has a potential E.sub.4 that is lower than the potential E.sub.1 of the ion guide 14. Further, by application of a voltage to each electrode plate included in the ion transport optical system 16 from the ion transport optical system voltage generating unit 32, the average potential of the entire ion transport optical system 16 has the same potential as that of the entrance-side electrode 171. Although potentials at the installation locations of the respective electrode plates in the ion transport optical system 16 are not the same, the potential can be regarded as constant when considered on an average basis, and therefore in FIG. 2B the potential distribution is represented by a dashed line.

(20) The solid line U3 illustrated in FIG. 2B represents a schematic potential distribution when ions that had been held in the linear ion trap are released. At this time, the exit-side gate electrode voltage generating unit 31 significantly reduces the voltage applied to the exit-side gate electrode 132. Further, the ion transport optical system voltage generating unit 32 significantly reduces the voltage applied to the respective electrode plates included in the ion transport optical system 16 by an amount that corresponds to the amount by which the voltage applied to the exit-side gate electrode 132 was reduced. However, a potential difference across the respective electrode plates constituting the ion transport optical system 16 is maintained so as to form an electric field exhibiting a lens effect which focuses ions that attempt to pass through the central apertures of the electrode plates. Therefore, although the potentials at the installation locations of the respective electrode plates in the ion transport optical system 16 are not the same, the potential can also be regarded as constant when considered on an average basis, and hence in FIG. 2B the potential distribution is represented by a dashed line.

(21) By this means, the average potential of the overall ion transport optical system 16 becomes a potential E.sub.3 that is far lower than the potential E.sub.4 of the entrance-side electrode 171. A potential barrier at the exit-side gate electrode 132 also disappears. Then, an accelerating electric field that exhibits a potential gradient having a sharp downward slope is formed from an exit-side end of the ion guide 14 toward an entrance-side end face (first-stage electrode plate) of the ion transport optical system 16. The ions that had been held in the internal space of the internal space of the ion guide 14 until immediately prior thereto are accelerated by the accelerating electric field.

(22) The thin alternate long and short dash line U2 shown in FIG. 2B represents a potential distribution during ion release based on the apparatus disclosed in Patent Literature 1. Although in this case also ions that have been held in the ion guide 14 are accelerated by an accelerating electric field, it can be seen that the slope of the potential gradient in the accelerating electric field is gentle, and the acceleration energy imparted to the ions is small. In the Q-TOFMS of the present embodiment, as shown in FIG. 2B, the slope of the potential gradient in the accelerating electric field is made large by making the difference large between the potential at the exit-side end of the ion guide 14 and the potential at the entrance-side end face of the ion transport optical system 16, and a large amount of acceleration energy is thus imparted to the respective ions that pass through the electric field. Since the amount of acceleration energy received by the respective ions is the same irrespective of the mass-to-charge ratios, each ion has a velocity depending on the mass-to-charge ratio of the ion.

(23) When the amount of acceleration energy is large, the velocity of each ion increases by a corresponding amount, and the lamer that the velocity is overall, the more difficult it is for a time difference due to a velocity difference to arise when ions travel by a unit distance. In other words, the larger that the velocity is overall, the less likely it is for a distance difference to arise between ions with a small mass-to-charge ratio that have a comparatively high velocity and ions with a large mass-to-charge ratio that have a comparatively low velocity. Therefore, ions having different mass-to-charge ratios pass through the ion transport optical system 16 without large position differences depending on the mass-to-charge ratios, that is, without broadly spreading in the ion travel direction. As described above, in the ion transport optical system 16, by adjusting a voltage applied to each electrode plate, a lens effect for ions is produced. Therefore, ions efficiently pass though the ion transport optical system 16 without significantly spreading in the radial direction of the axis C.

(24) The ion guide 14 has an internal space that is long in the axis C direction. If the positions of ions vary significantly in the axial direction when the ions are being held in the internal space of the ion guide 14, when the ions are released from the ion guide 14, spreading of ions is liable to occur in the axial direction due to differences in the time taken for the ions to arrive at the accelerating electric field. Therefore, when holding ions in the internal space of the ion guide 14 (or at least immediately prior to releasing the ions), it is preferable that the ions are gathered at a position close to the exit-side end of the ion guide 14. To achieve such a state, a potential gradient in the axial direction can be formed utilizing the configuration disclosed in Patent Literature 3.

(25) As a result of the average potential of the entire ion transport optical system 16 being the potential E.sub.3 that is lower than the potential E.sub.4 of the entrance-side electrode 171, a decelerating electric field exhibiting a potential gradient with a sharp upward slope is formed between the exit-side end face (electrode plate at the final stage) of the ion transport optical system 16 and the entrance-side electrode 171. Accordingly, ions that pass through the ion transport optical system 16 enter the decelerating electric field and the energy of the ions decreases. In other words, according to the Q-TOFMS of the present embodiment, ions are accelerated in the accelerating electric field created between the exit-side end of the ion guide 14 and the entrance-side end face of the ion transport optical system 16, and thereafter the ions are decelerated in a decelerating electric field created between the exit-side end face of the ion transport optical system 16 and the entrance-side electrode 171. However, because the potential difference (E.sub.4E.sub.3) in the decelerating electric field is smaller than the potential difference (E.sub.1E.sub.3) in the accelerating electric field, ions that are decelerated in the decelerating electric field are introduced to the orthogonal acceleration unit 17 at an appropriate velocity. Although the spread of the ions in the ion travel direction is broadened due to deceleration, the ions enter the orthogonal acceleration unit 17 immediately after deceleration, and thus spreading of the ions in the X-axis direction in accordance with the mass-to-charge ratios of the ions is suppressed.

(26) The orthogonal acceleration unit voltage generating unit 33 applies to the exit-side auxiliary electrode 174 a voltage Vb that is a little higher than a voltage Va that is applied to the entrance-side electrode 171 during a period until a predetermined delay time elapses from a time point at which the ions are released from the ion guide 14 upon lowering the voltage applied to the exit-side gate electrode 132 and the ion transport optical system 16 in a pulse form. At this time, a voltage need not be applied to the push-out electrode 172, or an appropriate voltage within the voltages Va and Vb may be applied to the push-out electrode 172. As a result, in the space between the entrance-side electrode 171 and the exit-side auxiliary electrode 174, a DC electric field having an upward potential gradient for the ions is created along the axis C as shown in FIG. 3B.

(27) The ions that have passed through the entrance-side electrode 171 ascend and travel the upward gradient, which gently decelerates the ions. For the ions that have relatively small mass-to-charge ratios that enter first, the earlier that the ions enter, the greater the degree of deceleration is, while on the other hand the ions that have relatively large mass-to-charge ratios which enter with a delay are not decelerated very much. As a result, after the ions enter the orthogonal acceleration unit 17 while spreading in the X-axis direction (direction of the axis C) as illustrated in FIG. 3C, the packet of ion is compressed in the X-axis direction as illustrated in FIG. 3D. In other words, after entering the orthogonal acceleration unit 17, the spread of ions in the X-axis direction due to the mass-to-charge ratios is further reduced.

(28) The orthogonal acceleration unit voltage generating unit 33 applies a predetermined acceleration voltage to each of the push-out electrode 172 and the pull-out electrode 173 at a timing after a predetermined delay time from a time point at which the ions are released from the ion guide 14 upon lowering the voltage applied to the exit-side gate electrode 132 and the ion transport optical system 16 in a pulse form. As a result, the ions that had been proceeding through the orthogonal acceleration unit 17 in the X-axis direction are accelerated in the Z-axis direction. At this time, ions existing in a predetermined length (a length P of the accelerating region in FIG. 2A) in the X-axis direction are accelerated. Because spreading of the ions in the X-axis direction due to the mass-to-charge ratios is suppressed as described above, it is possible to accelerate the ions at a time when ions of a broad range of mass-to-charge ratios are present in the aforementioned length P by appropriately setting the delay time. That is, ions having a broad range of mass-to-charge ratios can be sent into the flight space 20 without wasting ions, and a mass spectrum across a broad range of mass-to-charge ratios can be obtained.

(29) Further, although each ion before deceleration has a large amount of energy, the energy of each ion significantly decreases through the decelerating electric field. If ions with a large amount of energy are introduced into the orthogonal acceleration unit 17, when the ions are accelerated in the Z-axis direction the ions will fly out while keeping a large velocity component in the X-axis direction, and hence the trajectory of the ions will significantly deviate from the Z-axis direction. In this regard, in the Q-TOFMS of the present embodiment, because ions enter the orthogonal acceleration unit 17 in a state in which the energy of each ion is sufficiently decreased, deviation of the trajectory of the ions from the Z-axis direction can be suppressed. As a result, changes in the flight distance are small, and the accuracy of the mass-to-charge ratios that are calculated based on the times of flight can be increased.

(30) As described above, in the Q-TOFMS of the present embodiment, a mass spectrum (product ions spectrum) of a broad range of mass-to-charge ratios can be obtained with high sensitivity and high accuracy by a single measurement.

(31) When the degree of spreading of ions in the ion travel direction depending on mass-to-charge ratios in introducing the ions into the orthogonal acceleration unit 17 is changed, the mass-to-charge ratio range of mass spectrum data obtained by a single measurement changes. The aforementioned degree of spreading of ions is mainly determined by the magnitude of acceleration energy imparted to the ions in the accelerating electric field (that is, the potential difference in the accelerating electric field), the length in the axis C direction of the ion transport optical system 16, the length P of the accelerating region in the orthogonal acceleration unit 17, and a difference between the applied voltage Va to the entrance-side electrode 171 and the applied voltage Vb to the exit-side auxiliary electrode 174 when ions enter the orthogonal acceleration unit 17 or the like. Therefore, a configuration may be adopted in which the relation between these factors is determined in advance and, for example, control such as adjusting the magnitude of the acceleration energy or the degree of deceleration in the orthogonal acceleration unit 17 in response to the desired mass-to-charge ratio range is performed.

(32) A configuration other than the foregoing configuration can also be adopted to create an electric field having a rising potential gradient as described above when ions enter the orthogonal acceleration unit 17. FIG. 4 and FIG. 5 are views that illustrate such modifications.

(33) FIG. 4 and FIG. 5 show modified configurations of the push-out electrodes for acceleration. In the example illustrated in FIG. 4, a push-out electrode 175 consists of a resistive element or is made by forming a resistive layer on the surface of a conductive material, and an electric field as described above is created by a difference between voltages applied to both ends thereof. When accelerating ions in the orthogonal direction, the same voltage may be applied to both ends of the push-out electrode 175. Meanwhile, in the example illustrated in FIG. 5, a push-out electrode 176 is forming by dividing an electrode into a plurality of electrodes and disposing the electrodes with predetermined intervals therebetween in the axis C direction. An electric field is created as described above by applying respectively different voltages (stepped voltages) to each of the divided electrodes. When accelerating ions in the orthogonal direction, the same voltage may be applied to all of the divided electrodes constituting the push-out electrode 176.

(34) Although in the foregoing embodiment the present invention is applied to a Q-TOFMS that uses an orthogonal acceleration TOFMS, the present invention can also be applied to a linear TOFMS or a reflectron TOFMS that adopts a three-dimensional quadrupole ion trap as an ion ejection source. In such a case, the orthogonal acceleration unit 17 in the configuration of the foregoing embodiment may be replaced with a three-dimensional quadrupole ion trap. In other words, a configuration may be adopted in which ions that pass through the ion transport optical system 16 and travel through the decelerating electric field are introduced from an entrance of the three-dimensional quadrupole ion trap inside the pertinent ion trap. In this case, although it is necessary to limit a time period in which ions that travel through the entrance are introduced inside the three-dimensional quadrupole ion trap to a specific range, by using the configuration of the above embodiment it is possible to introduce ions of a broader range of mass-to-charge ratios into the ion trap. As a result, a mass-to-charge ratio range of a mass spectrum obtained by subjecting ions captured in the ion trap to mass spectrometry can be widened.

(35) The previous embodiment is one example of the present invention, and any change, modification or addition appropriately made within the spirit of the present invention will naturally fall within the scope of claims of the present application.

REFERENCE SIGNS LIST

(36) 1 . . . Chamber 2 . . . Ionization Chamber 3, 4, 5 . . . Intermediate Vacuum Chamber 6 . . . High Vacuum Chamber 7 . . . ESI Spray 8 . . . Heating Capillary 9 . . . Ion Guide 10 . . . Skimmer 11 . . . Ion Guide 12 . . . Quadrupole Mass Filter 13 . . . Collision Cell 131 . . . Entrance-Side Gate Electrode 132 . . . Exit-Side Gate Electrode 14 . . . Ion Guide 15 . . . Ion Passage Opening 16 . . . Ion Transport Optical System 17 . . . Orthogonal Acceleration Unit 171 . . . Entrance-Side Electrode 172, 175, 176 . . . Push-Out Electrode 173 . . . Pull-Out Electrode 174 . . . Exit-side Auxiliary Electrode 20 . . . Flight Space 21 . . . Reflector 22 . . . Back Plate 23 . . . Ion Detector 30 . . . Controlling Unit 31 . . . Exit-Side Gate Electrode Voltage Generating Unit 32 . . . Ion Transport Optical System Voltage Generating Unit 33 . . . Orthogonal Acceleration Unit Voltage Generating Unit C . . . Axis