WO2019211886A1

WO2019211886A1 - Time-of-flight mass spectrometer

Info

Publication number: WO2019211886A1
Application number: PCT/JP2018/017386
Authority: WO
Inventors: 朝是大城
Original assignee: 株式会社島津製作所
Priority date: 2018-05-01
Filing date: 2018-05-01
Publication date: 2019-11-07
Also published as: JP6881679B2; JPWO2019211886A1

Abstract

According to the present invention, during MS/MS analysis, a collision energy (CE) greater than that for ordinary MS analysis is imparted to ions which are then introduced into a collision cell (13) where the ions are dissociated. Then, mass analysis is conducted by introducing the resultant product ions into an orthogonal accelerator (17) of an OA-TOFMS. The ions subject to mass analysis are temporarily accumulated in the interior space of an ion guide (14) by means of a potential barrier formed as a result of applying voltage to an exit-side gate electrode (132), while a control unit (30) controls a voltage generation unit (33) such that the potential barrier becomes increasingly higher with increase in CE. Even in the case when the CE is high, ions do not get past the potential barrier and are ensured to be accumulated in the interior space of the ion guide (14). Meanwhile, in the case when the CE is low, ions accumulate in clusters on the exit side of the ion guide (14), thereby resulting in an enhanced ion compression effect. With this configuration, it is possible to achieve an improved duty cycle and an enhanced ion detection sensitivity.

Description

Time-of-flight mass spectrometer

The present invention relates to a time-of-flight mass spectrometer (hereinafter referred to as “TOFMS” where appropriate), and more specifically, a quadrupole-flight for performing mass analysis by introducing ions dissociated by a collision cell into an orthogonal acceleration type TOFMS. The present invention relates to TOFMS such as a time-type mass spectrometer.

One method of TOFMS is a method of orthogonal acceleration (also called “vertical acceleration” or “orthogonal extraction”) in which ions are accelerated and sent into flight space in a direction substantially orthogonal to the traveling direction of the ion flow derived from the sample component. TOFMS (hereinafter referred to as “OA-TOFMS” where appropriate) is known. For example, in Patent Document 1 and Non-Patent Document 1, a quadrupole mass filter is disposed before the collision cell that dissociates ions by collision-induced dissociation, while an OA-TOFMS is disposed after the collision cell. A time-of-flight mass spectrometer (hereinafter referred to as “Q-TOFMS” as appropriate) is disclosed.

In the orthogonal acceleration part of OA-TOFMS, an acceleration voltage (“push-pull voltage” in Patent Document 1) for accelerating ions in a pulse manner is applied to the acceleration electrode at a predetermined timing. Only ions passing through the orthogonal acceleration part are accelerated toward the flight space, and other ions, that is, ions passing through the orthogonal acceleration part before or after applying the acceleration voltage are wasted. The utilization efficiency of ions in OA-TOFMS is generally called a duty cycle and is defined by the following equation (see Patent Document 2).
Duty Cycle [%] = {(Amount of ions actually used for measurement) / (Amount of ions reaching the orthogonal acceleration portion)} × 100

As can be seen from the above formula, when the ion flow is continuously introduced into the orthogonal acceleration section, the duty cycle becomes low. Therefore, in order to improve the duty cycle, in the conventional general Q-TOFMS, ions to be measured are temporarily accumulated in the collision cell, and the accumulated ions are discharged from the collision cell and compressed. A configuration is adopted in which the flow is intermittently sent to the orthogonal acceleration unit, and the ions are accelerated in the orthogonal acceleration unit in accordance with the timing at which the ion flow is supplied.

For example, in the Q-TOFMS described in Patent Document 3, the distance from the ion optical axis (center axis) gradually increases as the ions travel through the plurality of rod electrodes constituting the ion guide disposed in the collision cell. An axial potential distribution (strictly speaking, it is a pseudopotential distribution, but in this specification, the real potential derived from the pseudopotential and the DC voltage is referred to as “potential” for the sake of convenience). Is inclined downward in the ion traveling direction. Then, a potential barrier is formed in the space between the outlet end of the ion guide and the outlet side gate electrode by the direct current potential difference between the outlet side gate electrode provided at the outlet side opening of the collision cell, and the downward slope Ion can be accumulated in the space surrounded by the ion guide by the potential distribution and the potential barrier.

Furthermore, in the Q-TOFMS described in Document 3, the magnitude of the force that pushes back the ions to overcome the potential barrier is changed by changing the height of the potential barrier according to the mass-to-charge ratio of the ion to be measured. Thus, the dependence of the mass-to-charge ratio on the travel time for ions ejected from the collision cell to reach the orthogonal acceleration portion is reduced. This achieves a high duty cycle for ions having various mass to charge ratios.

US Pat. No. 6,285,027 JP 2010-170848 A International Publication No. 2016/042632 Pamphlet U.S. Pat. No. 7,456,388

However, according to the experimental study by the present inventors, even if the height of the potential barrier is adjusted according to the mass-to-charge ratio of the ion to be measured as described above, the duty cycle may not be improved. is there.

For example, in Q-TOFMS, MS / MS (= MS ² ) analysis can be performed for mass analysis of ions dissociated by collision-induced dissociation in the collision cell, but normal mass that does not dissociate ions in the collision cell. It is also possible to carry out an analysis (MS ¹ analysis). When the mass-to-charge ratio of the ions to be measured is approximately the same when performing MS / MS analysis and when performing MS ¹ analysis, the duty cycle can be set even if the potential barrier height for ion accumulation is the same. There is a clear difference. Therefore, for example, if the parameters are adjusted so that the duty cycle at the time of MS / MS analysis is as good as possible, the duty cycle at the time of MS ¹ analysis is lowered, and the detection sensitivity of ions is lowered accordingly.

The present invention has been made to solve the above-mentioned problems, and its object is to improve the duty cycle when performing either MS / MS analysis or MS ¹ analysis in a TOFMS such as Q-TOFMS. It is to provide a TOFMS capable of improving the sensitivity of the mass spectrum.

When performing MS / MS analysis in Q-TOFMS, a certain amount of energy (collision energy) is applied to the ions in order to dissociate the ions by contact with a predetermined gas (collision gas) in the collision cell. Must be introduced into the collision cell. On the other hand, when performing MS ¹ analysis in Q-TOFMS, ion dissociation is performed on ions introduced into the collision cell so that dissociation does not occur even if a predetermined gas is present in the collision cell. Small energy is given compared with the time of operation. As a result of experimental studies, the inventors have found that the height of the potential barrier for improving the duty cycle varies depending on the energy applied to the ions when introduced into the collision cell, that is, the collision energy. I found. And based on such knowledge, it came to complete this invention.

That is, the present invention made in order to solve the above-described problems includes a collision cell for bringing ions incident with a predetermined energy into contact with a predetermined gas, and ions discharged from the collision cell. A time-of-flight mass spectrometer comprising: an accelerating unit that accelerates in a direction different from the incident axis; and a separation detecting unit that separates and detects ions accelerated by the accelerating unit according to a mass-to-charge ratio. ,
a) An ion guide that is arranged inside the collision cell to focus ions near the ion optical axis by a high-frequency electric field in order to temporarily hold ions to be measured, and an exit end outside the ion guide. An ion holding unit including an exit-side gate electrode that is disposed and forms a part of the collision cell or is separate from the collision cell;
b) a voltage application unit for applying a DC voltage to the outlet side gate electrode;
c) When holding the ions to be measured in the internal space of the ion guide, a DC voltage during holding is set so that the potential at the outlet gate electrode is higher than at the outlet end of the ion guide. In addition to applying to the electrode, when discharging ions from the ion guide, a DC voltage at the time of discharge is applied to the outlet-side gate electrode so that the potential at the outlet-side gate electrode is lower than the outlet end of the ion guide. Preferably, the control unit controls the voltage application unit, and when the ion is introduced from the previous stage of the collision cell to the inside of the collision cell according to the magnitude of energy applied to the ion. A control unit for changing the DC voltage;
It is characterized by having.

In the present invention, the larger the energy applied to the ions introduced into the collision cell, that is, the collision energy, the more the ion to be measured is formed between the exit end of the ion guide and the exit-side gate electrode. The holding DC voltage is set so as to increase the potential barrier. Usually, the collision energy during MS / MS analysis is less than that during MS ¹ analysis (strictly speaking, it is not “collision energy” because ions are not dissociated during MS ¹ analysis, but for the sake of convenience in this specification, MS / MS analysis is performed. time, hereinafter) is high both collision energy when MS ¹ analysis, the potential barrier is higher than that in the MS ¹ analysis during MS / MS analysis.

When ions are introduced into the collision cell with a relatively small collision energy, the potential barrier formed between the exit end of the ion guide and the exit-side gate electrode is relatively low. Are not pushed back and tend to accumulate intensively near the exit in the ion guide. Therefore, when a direct current voltage at the time of emission is applied to the exit-side gate electrode and the potential barrier disappears, ions to be measured reach the acceleration part without being dispersed much. Thereby, the duty cycle can be improved. The acceleration unit is typically an orthogonal acceleration unit that accelerates ions in a direction orthogonal to the incident axis.

On the other hand, when ions are introduced into the collision cell with a relatively large collision energy, the potential barrier formed between the exit end of the ion guide and the exit-side gate electrode is relatively high. Ions introduced into the collision cell come into contact with the collision gas and dissociate to generate various product ions, which also have a relatively large energy. If the potential barrier formed between the exit end of the ion guide and the exit-side gate electrode is low, product ions having large energy may leak over the potential barrier. Therefore, product ions having large energy do not get over the potential barrier and are reliably accumulated. Thereby, loss of ions to be measured can be suppressed, and the duty cycle can be improved.

However, if the height of the potential barrier is changed, the force to push back the ions changes, so that there is a difference in the site where many ions exist in the internal space of the ion guide. Specifically, when the potential barrier is high, many ions are likely to exist in a portion closer to the entrance end in the internal space of the ion guide. Therefore, depending on the height of the potential barrier, there is a difference in the time (ion movement time) from when the potential barrier disappears until ions are emitted from the ion guide and reach the acceleration portion.

Therefore, in the present invention, preferably, the control unit changes the holding DC voltage from the time when the discharge DC voltage is applied to the outlet gate electrode until the acceleration is accelerated by the acceleration unit. It is preferable that the delay time be changed.

Specifically, even if the mass-to-charge ratio of ions to be measured is about the same, the delay time may be increased when the potential barrier is high compared to when the potential barrier is low. An appropriate delay time may be obtained in advance experimentally or by simulation. Thereby, the duty cycle can be further improved and ions can be detected with high sensitivity.

In the present invention, the MS / MS analysis mode for mass analysis of dissociated ions and the MS analysis mode for mass analysis of ions not to be dissociated can be selectively executed.
In the MS / MS analysis mode, energy is applied to the ions so that the ions introduced into the collision cell are dissociated when they come into contact with a predetermined gas. In the MS analysis mode, ions introduced into the collision cell are It is preferable that a lower energy than that at the time of dissociation is applied to the ions so that the dissociation does not occur when the gas contacts with a predetermined gas and cooling is performed.

In the present invention, in order to form a downwardly inclined potential distribution for transporting ions in the axial direction inside the ion guide, as disclosed in Patent Document 3, a plurality of rod electrodes constituting the ion guide. Is arranged not to be parallel to the ion optical axis but to be inclined with respect to the ion optical axis, the distance between the ion optical axis and the inner peripheral surface of the rod electrode in the plane orthogonal to the ion optical axis is directed in the ion traveling direction. It is good to gradually increase according to. Another method disclosed in Patent Document 4 may be used.

According to the present invention, the duty cycle can be improved regardless of whether the MS / MS analysis or the MS ¹ analysis is performed, and thereby the sensitivity of the mass spectrum can be improved. Also, when performing MS / MS analysis, the collision energy may be changed, for example, depending on the type of target compound or to change the mode of cleavage even for the same compound. The cycle can be brought close to the best so that a good mass spectrum can be obtained.

The block diagram of the principal part of Q-TOFMS which is one Example of this invention. The detailed block diagram (a) between the quadrupole mass filter and orthogonal acceleration part in Q-TOFMS of a present Example, and the figure (b) which shows schematic potential distribution of an axial direction. Explanatory drawing of the ion behavior in the ion guide internal space in Q-TOFMS of a present Example. The timing diagram of the applied voltage to the exit side gate electrode and the applied voltage of orthogonal acceleration in Q-TOFMS of a present Example. The figure which shows the actual measurement result of the relationship between the push-back voltage, delay time, and signal strength under different collision energy.

Hereinafter, Q-TOFMS which is an embodiment of the present invention will be described with reference to the accompanying drawings.

FIG. 1 is a configuration diagram of the main part of the Q-TOFMS of this embodiment. The Q-TOFMS of the present embodiment has a multi-stage differential exhaust system configuration, and in the chamber 1, an ionization chamber 2, a first intermediate vacuum chamber 3, and a second intermediate vacuum chamber, which are substantially at atmospheric pressure atmosphere. 4, a first analysis chamber 5 and a second analysis chamber 6 having the highest degree of vacuum are disposed.

The ionization chamber 2 is provided with an ESI spray 7 for performing electrospray ionization (ESI). When a liquid sample containing the target compound is supplied to the ESI spray 7, charged droplets are sprayed from the tip of the spray 7. In the process where the droplet breaks and the solvent evaporates, ions derived from the target compound are generated. The ionization method is not limited to this. For example, when the sample is a liquid, atmospheric pressure chemical ionization (APCI) method, atmospheric pressure photoionization (APPI) method, probe electrospray ionization (other than ESI) ( An atmospheric pressure ionization method such as PESI method can be used, and a MALDI method can be used when the sample is in a solid state, and an electron ionization (EI) method when the sample is in a gaseous state, A chemical ionization (CI) method or the like can be used.

Various ions generated in the ionization chamber 2 are sent to the first intermediate vacuum chamber 3 through the heating capillary 8, converged by the array type ion guide 9, and sent to the second intermediate vacuum chamber 4 through the skimmer 10. Further, the ions are converged by the multipole ion guide 11 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 quadrupole ion guide 14 that functions as a linear ion trap is provided are installed. Various ions derived from the sample are introduced into the quadrupole mass filter 12, and at the time of MS / MS analysis, a specific mass-to-charge ratio (or mass-to-charge ratio range) corresponding to the voltage applied to the quadrupole mass filter 12 is obtained. The ions that 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 the collision gas supplied from the outside into the collision cell 13 to generate various product ions.

The ion guide 14 functions as a linear ion trap, and product ions generated by dissociation are temporarily accumulated in the internal space of the ion guide 14. The temporarily accumulated ions are discharged from the collision cell 13 at a predetermined timing, and introduced into the second analysis chamber 6 through the ion passage port 15 while being guided by the ion transport optical system 16. The ion transport optical system 16 is disposed across the first analysis chamber 5 and the second analysis chamber 6 with the ion passage port 15 interposed therebetween.

In the second analysis chamber 6, an orthogonal acceleration unit 17 that is an ion emission source, a flight space 18 in which a reflector 19 is disposed, and an ion detector 20 are provided, and are orthogonal along the ion optical axis C. The ions introduced into the acceleration unit 17 in the X-axis direction are accelerated in the Z-axis direction at a predetermined timing to start flying. In the flight space 18, the ions first freely fly in the space where there is no electric field, and then are turned back by the reflected electric field formed by the reflector 19, and then freely fly in the space without the electric field and reach the ion detector 20 again. . The flight time from when the ions leave the orthogonal acceleration unit 17 until they reach the ion detector 20 depends on the mass-to-charge ratio of the ions. Therefore, a data processing unit (not shown) creates a time-of-flight spectrum indicating the relationship between the flight time and the ion intensity based on the detection signal from the ion detector 20, and converts the flight time to the mass-to-charge ratio based on the known calibration information. A mass spectrum is created by conversion.

2A is a detailed configuration diagram of components from the quadrupole mass filter 12 to the orthogonal acceleration unit 17 in FIG. 1, and FIG. 2B is a schematic potential distribution diagram in the axial direction. In FIG. 2B, the potential U ₁ in the ion guide 14 is not a potential distribution on the ion optical axis C, but a pseudo potential received when the ion beam outside the ion optical axis C is transported toward the exit side. It is a gradient, and the potential distribution other than the ion guide 14 substantially indicates the potential distribution on the ion optical axis C.

The quadrupole mass filter 12 includes four rod electrodes arranged in parallel to the ion optical axis C. However, here, only two rod electrodes located on the XZ plane including the ion optical axis C are depicted (the same applies to the following quadrupole ion guide 14). The quadrupole ion guide 14 is composed of four rod electrodes. These four rod electrodes are not parallel to the ion optical axis C as shown in FIG. In a), they are arranged so that the distance from the ion optical axis C gradually increases toward the right). The rear end surface of the collision cell 13 serves as an exit-side gate electrode 132, and the exit-side gate electrode 132 and the quadrupole ion guide 14 substantially function as a linear ion trap. The ion transport optical system 16 has a configuration in which a plurality of (in this example, five) disk-shaped electrode plates having a circular opening at the center are arranged along the ion optical axis C. The orthogonal acceleration unit 17 includes an entrance electrode 171, an extrusion electrode 172, and a grid-shaped extraction electrode 173.

Under the control of the control unit 30, the quadrupole mass filter voltage generation unit 31 applies a predetermined voltage to each rod electrode of the quadrupole mass filter 12. When an ion having a specific mass-to-charge ratio is selected by the quadrupole mass filter 12, this voltage is a voltage obtained by superimposing a high-frequency voltage on a DC voltage, and the DC voltage and the amplitude of the high-frequency voltage are the mass charges to be selected. Depending on the ratio. Further, a DC bias voltage is further added to a voltage obtained by synthesizing the DC voltage and the high frequency voltage. The ion guide voltage generator 32 applies a predetermined voltage to each rod electrode of the quadrupole ion guide 14. This voltage is obtained by adding a DC bias voltage to a high-frequency voltage for ion focusing. The outlet side gate electrode voltage generator 33 applies a predetermined DC voltage to the outlet side gate electrode 132. The ion transport optical system voltage generator 34 applies a predetermined DC voltage to each electrode plate included in the ion transport optical system 16. The orthogonal acceleration unit voltage generator 35 applies predetermined voltages to the inlet electrode 171, the extrusion electrode 172, and the extraction electrode 173, respectively.

Here, the energy applied to the ions introduced into the collision cell 13, that is, the collision energy, is the bias voltage applied to the rod electrode of the quadrupole mass filter 12 and the rod electrode of the quadrupole ion guide 14. It is determined by the voltage difference from the bias voltage applied to the. When performing MS / MS analysis in the Q-TOFMS of this embodiment, it is necessary to dissociate ions by collision-induced dissociation in the collision cell 13 as described above. And apply to the collision cell 13. On the other hand, when performing MS ¹ analysis in the Q-TOFMS of the present embodiment, in order to prevent ions from dissociating in the collision cell 13, a smaller collision energy is applied to the ions than during MS / MS analysis. To the collision cell 13. In MS ¹ analysis, ion dissociation is not performed in the collision cell 13, but in order to reduce the energy of ions introduced into the collision cell 13 and make it easy to be captured, an inert gas is used as a cooling gas in the collision cell 13. To introduce.

In the Q-TOFMS of this embodiment, ions introduced into the collision cell 13 or product ions generated by dissociating the introduced ions by collision-induced dissociation are introduced into the internal space of the quadrupole ion guide 14. Once accumulated, the accumulated ions are discharged from the collision cell 13 and introduced into the orthogonal acceleration unit 17 through the ion transport optical system 16 for mass analysis. The operation at that time will be described with reference to FIGS. 3 and 4 in addition to FIG. FIG. 3 is an explanatory diagram of ion behavior in the internal space of the quadrupole ion guide 14, and FIG. 4 is a timing diagram of the applied voltage to the exit-side gate electrode 132 and the applied voltage for orthogonal acceleration. Note that, here, the case where the ion to be measured is a positive ion is illustrated, but when the ion to be measured is a negative ion, it is obvious that the polarity of the voltage may be reversed between positive and negative.

When accumulating ions in the internal space of the quadrupole ion guide 14, the ion guide voltage generator 32 applies voltages obtained by adding a high frequency voltage and a DC voltage to the four rod electrodes constituting the ion guide 14. Apply. This high-frequency voltage is for forming a quadrupole high-frequency electric field that focuses ions near the ion optical axis C. On the other hand, the DC voltage is mainly for forming a potential distribution along the ion optical axis C and for applying collision energy to the ions as described above. Further, when ions are accumulated, the outlet-side gate electrode voltage generator 33 applies a predetermined DC voltage higher than that at the outlet end of the quadrupole ion guide 14 to the outlet-side gate electrode 132.

A solid line U ₅ shown in FIG. 2B is a schematic potential distribution on the ion optical axis C in the space between the exit end of the quadrupole mass filter 12 and the entrance end of the quadrupole ion guide 14. . A solid line U ₁ is an approximate potential distribution in the axial direction in the internal space when ions are accumulated in the internal space of the quadrupole ion guide 14. As described above, the ions introduced into the collision cell 13 are given collision energy by the downward gradient potential distribution indicated by the solid line U ₅ . In addition, since the rod electrode of the quadrupole ion guide 14 has the characteristic arrangement as described above, the potential distribution on the axis in the internal space of the ion guide 14 gradually decreases from the entrance end to the exit end. The shape is inclined downward.

On the other hand, as indicated by a one-dot chain line U ₂ in FIG. 2B, the potential at the position of the exit-side gate electrode 132 is higher than the potential at the exit end of the quadrupole ion guide 14. A potential barrier is formed in the space between the outlet end 14 (the position of the point P ₁ in FIG. 2B) and the outlet-side gate electrode 132 (the position of the point P ₂ in FIG. 2B). ing.

As described above, the ions introduced into the collision cell 13 or the product ions generated by dissociation in the collision cell 13 have a gentle downward gradient potential distribution formed in the internal space of the quadrupole ion guide 14. To move in the ion traveling direction (right direction in FIG. 2). And when it reaches the exit end of the quadrupole ion guide 14, it is pushed back by the potential barrier. Here, the control unit 30 controls the exit-side gate electrode voltage generation unit 33 so as to change the voltage applied to the exit-side gate electrode 132 in accordance with the collision energy applied to the ions introduced into the collision cell 13. . Specifically, the higher the collision energy, the higher the voltage applied to the outlet side gate electrode 132. Thereby, the potential barrier increases as the collision energy increases.

Two two-dot chain lines U _{2 in} FIG. 2B indicate potential barriers having different heights. As described above, since the collision energy is different between the MS ¹ analysis and the MS / MS analysis, the higher one of the _two one-dot chain lines U ₂ has a relatively large collision energy. The lower one of the _two one-dot chain lines U ₂ indicates the potential barrier at the time of MS ¹ analysis with a relatively small collision energy.

FIG. 3A shows the behavior of ions when the potential barrier is high, that is, when the collision energy is relatively large, and FIG. 3B shows when the potential barrier is low, that is, when the collision energy is relatively small. It is a conceptual diagram which shows the behavior of the ion in a case.

The ions pushed back by the potential barrier climb the potential gradient indicated by the solid line U ₁ , and when reaching a certain position, the energy becomes zero and the direction is reversed, and then the potential gradient again decreases. As shown in FIG. 3A, when the potential barrier is high, the slope of the barrier is steep, so that the energy for pushing back ions is large, and the pushed-back ions are far from the exit end of the quadrupole ion guide 14 ( the position of the point P ₃₎ Back up. In addition, since the ions introduced into the collision cell 13 have a large collision energy, the ions generated by the dissociation may travel toward the exit of the collision cell 13 with a relatively large energy. Many. Therefore, if the potential barrier is low, ions may get over the potential barrier and leak from the collision cell 13. However, since the potential barrier is high here, ions having large energy can be pushed back with certainty. Thereby, it is possible to avoid a loss of ions and accumulate a large amount of ions in the internal space of the quadrupole ion guide 14.

On the other hand, as shown in FIG. 3B, when the potential barrier is low, the inclination of the barrier is relatively gentle, so that the energy for pushing back ions is small, and the pushed back ions are at the exit end of the quadrupole ion guide 14. It returns only to a position close to (position of point P ₃ '). That is, in this case, ions can be accumulated in a narrow space relatively close to the exit end of the ion guide 14. In addition, since the potential barrier is low, there is a possibility that ions have a large energy, the potential barrier may be overcome. However, since the collision energy imparted to the ions introduced into the collision cell 13 is small, the ions are low. The potential barrier will surely push you back. Therefore, a large amount of ions can be accumulated in a space near the exit end of the quadrupole ion guide 14.

After the ions are temporarily accumulated in this way, at a predetermined timing, the outlet-side gate electrode voltage generator 33 sets the voltage applied to the outlet-side gate electrode 132 to be lower than the voltage at the outlet end of the quadrupole ion guide 14. The voltage is lowered to a voltage value higher than the voltage applied to the first electrode plate of the ion transport optical system 16. A dotted line U ₃ shown in FIG. 2B is a schematic potential distribution between the exit end of the quadrupole ion guide 14 and the first electrode plate of the ion transport optical system 16 at this time.

As shown in FIG. 2 (b), the potential barrier is eliminated, and a potential gradient inclined downward from the exit end of the quadrupole ion guide 14 toward the ion transport optical system 16 is formed. The ions temporarily accumulated in the internal space of the guide 14 are released simultaneously toward the ion transport optical system 16. In order to transport ions while converging them in the vicinity of the ion optical axis C in the ion transport optical system 16, different voltages are applied to the electrode plates included in the ion transport optical system 16 from the ion transport optical system voltage generator 34. Strictly speaking, the potential at the installation position of each electrode plate is not the same, but since it can be considered to be constant on average, the potential distribution is shown by a dotted line in FIG. Yes.

As shown in FIG. 4, when a predetermined delay time t elapses from the time when ions are ejected from the quadrupole ion guide 14 (that is, the collision cell 13), the orthogonal acceleration unit voltage generator 35 is pushed out. An acceleration voltage is applied to the electrode 172 and the extraction electrode 173 in a pulse manner. The delay time t at this time is determined as described later. When an acceleration voltage is applied in the orthogonal acceleration unit 17, ions to be measured are introduced into the orthogonal acceleration unit 17 and exist in the space between the extrusion electrode 172 and the extraction electrode 173. Thereby, in the Q-TOFMS of the present embodiment, the ions to be measured can be reliably ejected toward the flight space 18 and used for mass analysis.

Next, as a result of experimentally confirming that the intensity of ions derived from the target sample component can be increased by changing the height of the potential barrier during ion accumulation according to the collision energy as described above. explain.
FIG. 5 shows the process from the discharge of ions from the collision cell 13 to the ejection of ions by the orthogonal acceleration unit 17 in the MS ¹ analysis mode in which the collision energy (CE) is 5 eV and the MS / MS mode in which the collision energy is 20 eV. It is a figure which showed the peak intensity of the ion actually measured when the delay time t was taken on a horizontal axis and the folding voltage in the exit of the collision cell 13 was taken on the vertical axis by a contour line. The compound to be measured is Na ⁺ (NaI) (m / z 172). Here, the “push-back voltage” is a voltage corresponding to the height of the potential barrier described above.

5A and 5B, the region indicated by the diagonal lattice pattern is the region having the highest ion intensity. From this result, it can be seen that when CE = 5 eV, the ionic strength is maximized when the push-back voltage is about 2V, and when CE = 20 eV, the ionic strength is maximized when the push-back voltage is about 7V. The duty cycle is estimated to be the best when the ionic strength is maximized. Therefore, it can be seen from this result that the duty cycle can be improved and the ion detection sensitivity can be improved by appropriately changing the height of the potential barrier during ion accumulation according to the collision energy.

Also, from FIG. 5, it can be seen that the delay time t when the ion intensity is maximized is also clearly different depending on the collision energy. That is, in this measurement example, when CE = 5 eV, the delay time t is 18 to 19 us, and when CE = 20 eV, the delay time t is about 22 to 23 us and the ion intensity becomes maximum. This is because, as described above, when the collision energy is large and the potential barrier is high, the ions are pushed back more largely, so that the starting position when ions are ejected from the collision cell 13 is entirely a quadrupole ion guide. It is presumed that it is due to the side closer to the entrance of 14. For this reason, the orthogonal acceleration voltage generator 35 may change the timing of applying the acceleration voltage to the extrusion electrode 172 and the extraction electrode 173 according to the collision energy or the height of the potential barrier. That is, when the collision energy is large, the delay time t is longer than that when the collision energy is small, and ions that reach the orthogonal acceleration unit 17 with a little delay compared with the case where the collision energy is small are preferably accelerated.

In the above description, the MS ¹ analysis and the MS / MS analysis, which are the most typical examples when the collision energies are different from each other, have been described. However, when the MS / MS analysis is performed, the collision energy is determined according to the target compound. It is generally performed to obtain different peak pattern mass spectra by changing or dissociating different compounds in different modes by changing the collision energy at the time of MS / MS analysis. Even in such a case, it is clear that the duty cycle can be improved and the ion detection sensitivity can be improved by appropriately changing the height of the potential barrier during ion accumulation according to the collision energy and changing the delay time t. is there.

In the above embodiment, the present invention is applied to Q-TOFMS using OA-TOFMS. However, ions are accelerated in a direction different from the incident direction, such as an oblique direction rather than a direction orthogonal to the ion incident axis. Obviously, the present invention can be applied to an apparatus having a TOFMS configured to be injected.

Further, the above-described embodiment is merely an example of the present invention, and it is obvious that any change, modification, addition or the like as appropriate within the scope of the present invention is included in the scope of the claims of the present application.

DESCRIPTION OF SYMBOLS 1 ... Chamber 2 ... Ionization chamber 3 ... 1st intermediate | middle vacuum chamber 4 ... 2nd intermediate | middle vacuum chamber 5 ... 1st analysis chamber 6 ... 2nd analysis chamber 7 ... ESI spray 8 ... Heating capillary 9 ... Array type ion guide 10 ... Skimmer DESCRIPTION OF SYMBOLS 11 ... Multipole type ion guide 12 ... Quadrupole mass filter 13 ... Collision cell 132 ... Exit side gate electrode 14 ... Quadrupole type ion guide 15 ... Ion passage port 16 ... Ion transport optical system 17 ... Orthogonal acceleration part 171 ... Entrance electrode 172 ... Extrusion electrode 173 ... Extraction electrode 18 ... Flight space 19 ... Reflector 20 ... Ion detector 30 ... Control part 31 ... Quadrupole mass filter voltage generation part 32 ... Ion guide voltage generation part 33 ... Exit side gate electrode voltage Generator 34 ... Ion transport optical system voltage generator 35 ... Orthogonal accelerator voltage generator C ... Ion optical axis

Claims

A collision cell for bringing ions incident with a predetermined energy into contact with a predetermined gas, an accelerating unit for accelerating ions ejected from the collision cell in a direction different from the incident axis of the ion flow, and the acceleration A time-of-flight mass spectrometer comprising: a separation detection unit that separates and detects ions accelerated by the unit according to a mass-to-charge ratio;
a) An ion guide that is arranged inside the collision cell to focus ions near the ion optical axis by a high-frequency electric field in order to temporarily hold ions to be measured, and an exit end outside the ion guide. An ion holding unit including an exit-side gate electrode that is disposed and forms a part of the collision cell or is separate from the collision cell;
b) a voltage application unit for applying a DC voltage to the outlet side gate electrode;
c) When holding the ions to be measured in the internal space of the ion guide, a DC voltage during holding is set so that the potential at the outlet gate electrode is higher than at the outlet end of the ion guide. In addition to applying to the electrode, when discharging ions from the ion guide, a DC voltage at the time of discharge is applied to the outlet-side gate electrode so that the potential at the outlet-side gate electrode is lower than the outlet end of the ion guide. Preferably, the control unit controls the voltage application unit, and when the ion is introduced from the previous stage of the collision cell to the inside of the collision cell according to the magnitude of energy applied to the ion. A control unit for changing the DC voltage;
A time-of-flight mass spectrometer.
The time-of-flight mass spectrometer according to claim 1,
When the energy applied to the ions introduced into the collision cell is relatively large, the control unit sets the holding DC voltage to a relatively large value, and when the energy is relatively small, The time-of-flight mass spectrometer is characterized in that the voltage application unit is controlled so that the holding DC voltage is a relatively small value.
The time-of-flight mass spectrometer according to claim 1,
The control unit changes a delay time from when the DC voltage at the time of emission is applied to the exit-side gate electrode to when ions are accelerated by the acceleration unit, as the DC voltage at the time of holding is changed. A time-of-flight mass spectrometer.
The time-of-flight mass spectrometer according to any one of claims 1 to 3,
MS / MS analysis mode for mass analysis of dissociated ions and MS analysis mode for mass analysis of non-dissociated ions can be selectively performed, and the MS / MS analysis mode was introduced into the collision cell. Energy is given to the ions so that they dissociate when they come into contact with a predetermined gas. In the MS analysis mode, when ions introduced into the collision cell come into contact with a predetermined gas, they are cooled without dissociation. A time-of-flight mass spectrometer characterized in that energy lower than that at the time of dissociation is applied to the ions.