JP7452348B2 - Ion introduction method into an ion trap, ion trap mass spectrometer, and ion trap mass spectrometry program - Google Patents

Description

The present invention relates to a method for introducing ions from a sample into an ion trap that traps ions using an electric field, an ion trap mass spectrometer, and a computer program for ion trap mass spectrometry.

2. Description of the Related Art Mass spectrometers that use an ion trap that traps (confines) ions using an electric field are known. In an ion trap mass spectrometer, after capturing the ions to be analyzed in the ion trap, the ions are separated using the mass separation function of the ion trap itself to determine the mass-to-charge ratio (more specifically, "m/z" in italics). However, in this specification, they are separated according to the "mass-to-charge ratio" or "m/z" and detected by a detector. Further, in an ion trap time-of-flight mass spectrometer, after capturing ions to be analyzed in an ion trap, the ions are ejected all at once from the ion trap and introduced into a time-of-flight mass separator. Then, while the ions fly in the flight space of the time-of-flight mass separator, the ions are separated according to their mass-to-charge ratio and detected by a detector. In the following description, all mass spectrometers using ion traps, including ion trap mass spectrometers and ion trap time-of-flight mass spectrometers, will be referred to as ion trap mass spectrometers.

A typical ion trap is a three-dimensional quadrupole type ion trap that includes one approximately annular ring electrode and a pair of end cap electrodes arranged to sandwich the ring electrode. It's a trap. In a three-dimensional quadrupole type ion trap, by applying a predetermined radio frequency voltage (RF (Radio Frequency) voltage) to the ring electrode, a quadrupole radio frequency electric field is created in the space surrounded by the ring electrode and the end cap electrode. and can confine ions. Conventional general ion traps use a sinusoidal voltage as the RF voltage, but recently, ion traps that use a rectangular wave voltage as the RF voltage are also known (see Non-Patent Document 1, etc.). Such an ion trap is called a digital ion trap, to distinguish it from an ion trap that uses a sinusoidal RF voltage.

In an ion trap mass spectrometer, ions are usually introduced into the ion trap in the form of a packet, that is, in a lump. ) method is often used. In the MALDI ion source, the amount of ions generated by one pulsed laser beam irradiation is relatively small, and the amount of ions generated for each laser beam irradiation varies relatively widely. Therefore, in an ion trap mass spectrometer using a MALDI ion source, ions generated by irradiation with a laser beam are captured in an ion trap and subjected to mass analysis for a single sample, so that a predetermined mass-to-charge ratio range is obtained. The desired mass spectrum is created by collecting data many times and integrating the obtained data. According to this method, the signal quality of the mass spectrum, such as the SN ratio, is improved. On the other hand, there is a problem that it takes a long time to obtain a mass spectrum for one sample.

On the other hand, Patent Document 1 and Non-Patent Document 2 disclose techniques for additionally introducing ions into the ion trap from the outside while capturing ions in the ion trap. This technique takes advantage of the digital ion trap's ability to easily and quickly change the frequency of the square wave RF voltage used to form the trapping electric field.

Specifically, various ions derived from a sample are captured in an ion trap and then cooled to sufficiently reduce the energy of the ions. Subsequently, by increasing the frequency of the rectangular wave RF voltage applied to the ring electrode for ion trapping, the pseudopotential well formed inside the ion trap is temporarily made shallower. Although this reduces the restraining force of the electric field on the trapped ions, the energy of these ions has become sufficiently low that they continue to remain inside the ion trap.

On the other hand, since the pseudo- potential well has become shallower, ions can more easily enter the ion trap from the outside, making it possible to additionally introduce ions from the outside. Therefore, newly generated ions are guided into the ion trap by irradiating the sample with laser light. When the packet-shaped ions come near the center of the ion trap, that is, near the center (bottom) of the pseudopotential well, the frequency of the square wave RF voltage is returned to its original state, and the pseudopotential well is deepened. to capture newly introduced ions. Through such a series of operations, new ions can be added to and trapped in the ions already trapped inside the ion trap.

According to the above-described additional ion introduction method, even when the amount of ions generated in the ion source is small, the amount of ions captured in the ion trap can be increased, and detection in one mass spectrometry Sensitivity can be improved. Thereby, measurement time can be shortened and measurement throughput can be improved.

Further, as a method for additionally introducing ions into an ion trap, a method described in Patent Document 5 is also known. The ions trapped in the ion trap move back and forth between the outer periphery and the center of the trapping region during one cycle of the square wave RF voltage, meaning that the ion cloud, which is a collection of ions, expands. It moves so that a state in which it is closed and a state in which it is contracted in the center are alternately generated. At the timing when ions are about to head from the outer periphery toward the center within the trapping region, an electric field acts on ions that are about to enter the ion trap from the outside so as to direct the ions toward the ions. Therefore, in the method described in Patent Document 5, instead of changing the depth of the pseudopotential well, the inside of the ion trap is The supply timing of ions is controlled so that new ions are incident on the ion. Specifically, ions are made to enter the ion trap in synchronization with the timing of a specific phase or level change during one cycle of the rectangular wave RF voltage. Thereby, new ions can be efficiently introduced into the ion trap while suppressing the dissipation of ions that have been captured in the ion trap.

International Publication No. 2008/129850 US Patent No. 6,900,433 Japanese Patent Application Publication No. 2003-16991 International Publication No. 2014/038672 International Publication No. 2008/126383

Osamu Furuhashi, 6 others, “Development of digital ion trap mass spectrometer”, Shimadzu Review, Vol. 62, No. 3 and 4, 2005 ``Cutting-edge research and development support program ``Development of next-generation mass spectrometry systems and contribution to drug discovery and diagnosis'' research results report ``§2 Research objectives and results of each group'' 2 §2-1-3 Hardware development'', [online], [searched on July 9, 2020], Shimadzu Corporation, Internet <URL: https://www.shimadzu.co.jp/aboutus/ms_r/archive/files/tanaka-pj_report/tanaka-pj_report2 .pdf＞ F.L. Brancia and 4 others, “Digital Asymmetric Waveform Isolation (DAWI) in a Digital Linear Ion Trap” )”, Journal of American Society for Mass Spectrometry, 2010, 21, pp. 1530-1533

In principle, there is no limit to the number of times ions can be added to the ion trap using the method described above, but in reality, when a certain number of ions are captured in the ion trap, New ions are less likely to enter the ion trap due to space charge effects caused by trapped ions. In particular, a three-dimensional quadrupole ion trap has a narrower space in which ions can be trapped than a linear ion trap. Therefore, there is a problem that the influence of the space charge effect is large, the amount of ions that can be added is limited, and it is difficult to obtain effects such as shortening measurement time and improving throughput.

Further, in the ion trap mass spectrometer, MS ⁿ analysis (n is an integer of 2 or more) can be performed by dissociating ions in the ion trap by collision-induced dissociation (CID) or the like. In MS ⁿ analysis, an ion dissociation operation is performed after precursor selection to select ions with a specific mass-to-charge ratio, so the amount of product ions that are the target of mass spectrometry is often small, which is different from normal mass spectrometry. It is disadvantageous in terms of detection sensitivity compared to . In recent years, mass spectrometry has been increasingly used to analyze the structures of biologically derived compounds such as peptides, lipids, and sugar chains, and MS ⁿ analysis has become almost essential for such analyses. How to improve detection sensitivity in MS ⁿ analysis is one of the most important issues.

The present invention has been made to solve the above ^{-mentioned problems, and its purpose is to efficiently increase the amount of ions used in MS n analysis} to improve detection sensitivity. An object of the present invention is to provide a method for introducing ions into an ion trap, an ion trap mass spectrometer, and a program for ion trap mass spectrometry, which can improve the performance of the ion trap.

One aspect of the method for introducing ions into an ion trap according to the present invention, which has been made to solve the above problems, traps ions in the internal space by the action of an electric field formed in the internal space surrounded by a plurality of electrodes. A method of introducing ions from the outside into an ion trap,
While ions are captured in the internal space of the ion trap, target ions having a predetermined mass-to-charge ratio or a group of target ions whose mass-to-charge ratio falls within a predetermined mass-to-charge ratio range are left in the internal space, and other an ion selection step of ejecting ions from the interior space;
After performing the ion selection step, temporarily lowering the pseudopotential for trapping ions in the internal space, and introducing new ions from the outside into the internal space while maintaining the trapped ions. or an additional ion introduction step of increasing the amount of trapped ions by introducing new ions from the outside into the internal space at a predetermined timing according to the movement of the trapped ions;
It is intended to carry out the following.

Further, one aspect of the ion trap mass spectrometer according to the present invention, which was made to solve the above problems, is as follows:
an ion trap that traps ions in an internal space surrounded by a plurality of electrodes by the action of an electric field formed in the internal space;
a voltage generator that applies a predetermined voltage to each of the plurality of electrodes;
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. Changing the voltage applied to at least one of the plurality of electrodes so as to leave a group of target ions within the mass-to-charge ratio range in the internal space and eject other ions from the internal space, and then changing the voltage applied to at least one of the plurality of electrodes. At least one of the plurality of electrodes is configured to temporarily lower the pseudopotential for trapping ions in the internal space, and introduce new ions from the outside into the ion trap while maintaining the trapped ions. a control unit that changes the voltage applied to one;
It is equipped with the following.

Further, other aspects of the ion trap mass spectrometer according to the present invention, which have been made to solve the above problems, are as follows:
an ion supply unit that supplies ions in a pulsed manner;
an ion trap that traps ions in an internal space surrounded by a plurality of electrodes by the action of an electric field formed in the internal space;
a voltage generator that applies a predetermined voltage to each of the plurality of electrodes;
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. Changing the voltage applied to at least one of the plurality of electrodes so as to leave a group of target ions within the mass-to-charge ratio range in the internal space and eject other ions from the internal space, and then capturing the target ions. a control unit that controls the timing of pulsed ion supply in the ion supply unit so as to introduce new ions from the outside into the internal space at a predetermined timing according to the movement of the ions being moved;
It is equipped with the following.

Further, one aspect of the ion trap mass spectrometry program according to the present invention, which has been made to solve the above problems, is to inject ions into the internal space by the action of an electric field formed in the internal space surrounded by a plurality of electrodes. A computer program for driving an ion trap mass spectrometer comprising an ion trap for trapping and a voltage generation section for applying a predetermined voltage to each of the plurality of electrodes, the computer program comprising:
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. The voltage generating section changes the voltage applied to at least one of the plurality of electrodes so that a group of target ions falling within a mass-to-charge ratio range is left in the internal space and other ions are ejected from the internal space. an ion selection step to control the
After performing the ion selection step, the pseudopotential for trapping ions in the internal space is temporarily lowered, and new ions are introduced from the outside into the ion trap while maintaining the trapped ions. an additional ion introduction step of changing the voltage applied to at least one of the plurality of electrodes,
This is what allows you to execute the following.

In addition, another aspect of the ion trap mass spectrometry program according to the present invention, which has been made to solve the above problems, includes an ion supply section that supplies ions in a pulsed manner, and an ion trap formed in an internal space surrounded by a plurality of electrodes. an ion trap for driving an ion trap mass spectrometer comprising an ion trap that traps ions in the internal space by the action of an electric field; and a voltage generator that applies a predetermined voltage to each of the plurality of electrodes. A computer program that causes a computer to
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. The voltage generating section changes the voltage applied to at least one of the plurality of electrodes so that a group of target ions falling within a mass-to-charge ratio range is left in the internal space and other ions are ejected from the internal space. an ion selection step to control the
After performing the ion selection step, a pulse-like signal is sent from the ion supply unit to introduce new ions into the internal space at a predetermined timing according to the movement of the ions trapped in the ion trap. an additional ion introduction step for supplying ions;
This is what allows you to execute the following.

The ion trap referred to here is not limited to its structure or configuration as long as it is an ion trap that can trap ions by the action of an electric field, but generally it is a three-dimensional quadrupole ion trap or a linear ion trap. It is.

For example, when performing standard MS ² analysis (MS/MS analysis), in the conventional ion trap mass spectrometer described above, ions are additionally introduced into the ion trap one or more times, and While accumulating as many ions as possible in the internal space of the system, ions that are targets for MS ² analysis are selected as precursor ions, and a dissociation operation such as CID is performed on the selected ions. When new ions are additionally introduced into the ion trap, various ions derived from the sample are accumulated in the internal space of the ion trap.

In contrast, in the present invention, prior to additionally introducing ions into the ion trap, an operation is performed to select ions to be targets for MS ² analysis as precursor ions. Therefore, when new ions are additionally introduced into the ion trap, only ions originating from the sample and serving as targets for MS ² analysis are accumulated in the internal space of the ion trap. In other words, unnecessary ions that are not targets for MS ² analysis are excluded even if they originate from the sample. Therefore, when trying to introduce new ions into the ion trap, the amount of ions trapped in the ion trap is smaller than in conventional devices, and the space charge effect caused by the trapped ions is also small. . As a result, the efficiency of additionally introducing ions into the ion trap improves, and the ion dissociation operation can be performed with more precursor ions trapped in the internal space of the ion trap.

In this way, according to the present invention, the influence of space charge effects caused by already trapped ions is reduced, the amount of ions subjected to MS ⁿ analysis is efficiently increased, and the detection sensitivity of product ions is improved. be able to. Furthermore, since the quality of the signal obtained in one mass spectrometry (product ion scan measurement) can be improved, the measurement time can be shortened and the measurement throughput can be further improved.

FIG. 1 is a block diagram of main parts of MALDI-DITMS, which is an embodiment of the present invention. A flowchart showing processing steps during MS ² analysis when additional ion introduction is not performed in MALDI-DITMS. A flowchart showing processing steps during MS ² analysis when additional ion introduction is performed in conventional MALDI-DITMS. 2 is a flowchart showing processing steps during MS ² analysis when additional ion introduction is performed in MALDI-DITMS of the present embodiment. 2 is a flowchart showing other processing steps during MS ² analysis when additional ion introduction is performed in MALDI-DITMS of the present embodiment. Mathieu's stability region diagram for explaining the ion ejection operation by DAWI. FIG. 7 is a diagram showing waveform diagrams and operations of main parts when additionally introducing ions. FIG. 7 is an explanatory diagram of timing when additionally introducing ions in a modified example.

Hereinafter, a matrix-assisted laser desorption ionization digital ion trap mass spectrometer (MALDI-DITMS), which is an embodiment of the ion trap mass spectrometer according to the present invention, will be described with reference to the accompanying drawings.

[Configuration of MALDI-DITMS of this embodiment]
FIG. 1 is a block diagram of the main parts of the MALDI-DITMS of this embodiment. This MALDI-DITMS is a mass spectrometer that uses a MALDI ion source as an ion source and a digital ion trap as a mass separator.

As shown in FIG. 1, this MALDI-DITMS includes a measurement section 1, a gas supply section 2, a main voltage generation section 3, an auxiliary voltage generation section 4, a data processing section 5, a control section 6, an input section 7, and a display section. 8.

The measurement unit 1 includes a box-shaped chamber 10 that is evacuated by a vacuum pump 11, and inside this chamber 10, there is a sample stage 13 on which a sample plate 14 is placed, an extraction electrode 16, and a quadrupole type chamber 10. A deflector 17, an ion trap 18, and an ion detector 19 are arranged. A transparent window 100 is provided on the wall surface (top surface) of the chamber 10 directly above the sample stage 13, and a laser irradiation unit 12 is arranged outside the window 100. The sample stage 13 is movable in two axial directions, the X-axis and the Y-axis shown in the figure, by a stage drive unit (not shown) including a motor and the like. Usually, the XY plane is a plane parallel to the installation surface of this apparatus, and the sample plate mounting surface of the sample stage 13 is also parallel to the XY plane.

The quadrupole deflector 17 consists of four rod electrodes extending in the Y-axis direction, and the traveling direction of ions is controlled in the space surrounded by the rod electrodes by a DC voltage applied to each rod electrode from a voltage generator (not shown). A deflection electric field is created that bends the curve approximately at right angles.

The ion trap 18 has a three-dimensional quadrupole configuration including one ring electrode 181 having a substantially annular shape and a pair of end cap electrodes 182 and 184 that are arranged opposite to each other with the ring electrode 181 in between. It is. An ion entrance hole 183 is formed in the entrance end cap electrode 182 located on the quadrupole deflector 17 side, and an ion exit hole 185 is formed in the exit end cap electrode 184.

A predetermined voltage is applied to the ring electrode 181 from the main voltage generator 3 and to the end cap electrodes 182 and 184 from the auxiliary voltage generator 4, respectively. The electric field thus formed allows ions to be trapped in the internal space surrounded by the ring electrode 181 and the end cap electrodes 182 and 184, and ions can be ejected from the internal space through the ion exit hole 185.

The main voltage generating section 3 includes, for example, a positive voltage generating section that generates a predetermined positive voltage and a negative voltage generating section that generates a predetermined negative voltage in order to generate a rectangular wave RF voltage as described later. and a switching section that generates a rectangular wave RF voltage by switching between a positive voltage and a negative voltage at high speed. By controlling the switching frequency and switching duty ratio of this switching section, the control section 6 can adjust the frequency and duty ratio of the rectangular wave RF voltage. On the other hand, the auxiliary voltage generating section 4 divides the frequency of the rectangular wave RF voltage by 1/N in response to an instruction from the control section 6, and generates a signal whose amplitude is much lower than that of the rectangular RF voltage, or a DC voltage. occurs.

The gas supply unit 2 includes a storage unit that stores inert gas such as helium (He), nitrogen gas (N ₂ ), and argon (Ar), and a flow rate adjustment unit that adjusts the flow rate of such gas. The inert gas is supplied to the interior space of the trap 18 as a cooling gas or collision gas.

The control unit 6 controls each component included in the measurement unit 1 in order to perform measurement according to a control program stored in the control program storage unit 60. That is, the actual control unit 6 is a computer such as a personal computer or a workstation, and its functions are realized by executing a dedicated control program installed on the computer. In that case, the input section 7 is a keyboard or pointing device attached to the computer, and the display section 8 is a display monitor.

[MS ² analysis operation when additional ion introduction is not performed]
First, the MS ² analysis operation when additional ions are not introduced into the ion trap 18 in the MALDI-DITMS of this embodiment will be described. FIG. 2 is a flowchart showing a series of processing (operations) at this time.

<Step S1: Ion generation step>
A sample 15 prepared by mixing an appropriate matrix with a sample to be analyzed is formed on the sample plate 14 , and the sample plate 14 is placed on the sample stage 13 . Thereafter, the inside of the chamber 10 is evacuated by the vacuum pump 11. When the inside of the chamber 10 reaches a predetermined vacuum state, the laser irradiation unit 12 emits a laser beam for a short time under the control of the control unit 6. This laser light passes through the window 100 and is irradiated onto the sample 15 on the sample plate 14 approximately perpendicularly. Irradiated with this laser light, the sample components in the sample 15 are vaporized and ionized.

<Step S2: Ion introduction step>
The generated ions are extracted upward from the vicinity of the sample plate 14 by the electric field formed by the extraction electrode 16, travel approximately in the Z-axis direction, and reach the quadrupole deflector 17. The deflection electric field formed by the quadrupole deflector 17 bends the trajectory of the ions by approximately 90 degrees, and the ions proceed approximately in the X-axis direction. The ions enter the internal space of the ion trap 18 through the ion entrance hole 183 and are once captured by the electric field formed by the rectangular RF voltage applied from the main voltage generating section 3 to the ring electrode 181.

<Steps S3 and S4: Ion trapping step and cooling step>
When ions are introduced into the ion trap 18, no trapping voltage is applied to the ring electrode 181, the entrance side end cap electrode 182 is maintained at zero voltage, and the exit side end cap electrode 184 is supplied with an appropriate DC current of the same polarity as the ions. A voltage is applied. As a result, when the ions that have entered the ion trap 18 advance to the vicinity of the ion exit hole 185, they are repelled by the electric field formed by the DC voltage applied to the exit end cap electrode 184, and the ions enter the entrance end cap electrode 182. Return to direction.

Prior to the ion introduction, helium or the like is introduced into the ion trap 18 as a cooling gas by the gas supply section 2. Immediately after the ions are introduced into the ion trap 18 as described above, the main voltage generating section 3 under the control of the control section 6 starts applying a predetermined rectangular wave RF voltage to the ring electrode 181 as a trapping voltage. . By applying the rectangular wave RF voltage, a trapping electric field is formed inside the ion trap 18 that traps ions while vibrating them. The introduced ions initially have relatively large energy, but as they collide with the cooling gas present in the ion trap 18, their energy is gradually taken away and they become more likely to be captured by the trapping electric field.

<Step S5: Precursor selection process>
After performing cooling for an appropriate time to stably capture ions in the internal space of the ion trap 18, in order to selectively leave ions having a specific mass-to-charge ratio among various ions as precursor ions. , and other ions are ejected from the ion trap 18. Such precursor ion selection methods can be performed using various conventionally known methods, such as those described in Patent Documents 2 to 4, Non-Patent Document 3, and the like.

Here, as an example, a precursor selection method proposed by the applicant in Japanese Patent Application No. 2019-199816 will be briefly described.
First, as a first step, a rough separation operation is performed in which ions with mass-to-charge ratios falling outside the range are left behind, and ions with mass-to-charge ratios outside of that range are excluded. Execute. For example, DAWI (Digital Asymmetric Waveform Isolation) can be used for this rough separation operation. DAWI is described in detail in Non-Patent Document 3, etc., but will be briefly explained here.

FIG. 6 is a stability region diagram created based on stability conditions for solutions to the well-known Mathieu equation. In FIG. 6, the diagonally shaded range surrounded by β _z =0, β _z =1 (not shown), β _r =0, and β _r =1 is where ions stably exist in the internal space of the ion trap. This is the stable region obtained.

In a normal ion trapping state, the horizontal line at a _z =0 in FIG. 6 becomes the operating line, and ions in a wide mass-to-charge ratio range fall within the stable region. In other words, ions having a wide mass-to-charge ratio range can be stably captured in the ion trap. When removing ions using DAWI or a similar ion selection method, the operating line is tilted diagonally upward to the right as shown by the thick arrow in FIG. Then, the operating line becomes as shown by a two-dot chain line, and only a part of it crosses the stable region. The point where this operating line intersects the boundary line of the stability region, specifically the point where it intersects β _z = 0, is the upper limit mass of ions that can be trapped inside the ion trap (HMCO = High Mass Cut Off). be. Further, the point where β _r =1 intersects is the lower limit mass (LMCO = Low Mass Cut Off) of ions that can be trapped inside the ion trap.

In DAWI, the lower limit mass and upper limit mass are changed by changing the duty ratio of the rectangular wave RF voltage applied to the ring electrode 181. The main voltage generator 3 can change the duty ratio of the rectangular wave RF voltage in a short time. Therefore, the DAWI method can eliminate unnecessary ions in a relatively short time. In the rough separation operation, it is preferable to leave ions within a range of, for example, ±3 to 5 Da around the mass-to-charge ratio of the precursor ion.

Following the rough separation operation, cooling is once performed to collect ions near the center of the internal space of the ion trap 18. Next, as one of the second stage ion selection steps with high mass resolution, an operation for removing unnecessary ions remaining on the lower mass side than the precursor ions is performed using the DAWI method. Specifically, under the control of the control unit 6, the main voltage generation unit 3 sets the duty ratio of the rectangular wave RF voltage applied to the ring electrode 181 to a predetermined value corresponding to the mass-to-charge ratio of the precursor ions. change it like this. Normally, when the duty ratio of the square wave RF voltage is 0.5, the operating line on the stability region diagram realized by the electric field formed in the ion trap 18 is the horizontal line at a _z = 0 in FIG. Become. As described above, when the duty ratio is changed, the operating line on the stability region diagram slopes upward to the right, and the lower limit mass changes. Therefore, by setting the duty ratio so that this lower limit mass is slightly lower than the mass-to-charge ratio of the desired precursor ion, unnecessary ions remaining on the side lower than the mass-to-charge ratio of the precursor ion can be eliminated. can do.

After that, cooling is performed to remove energy from the excited ions and collect them near the center of the internal space of the ion trap 18. As the next operation, DAWI is used to remove unnecessary ions remaining on the higher mass side than the precursor ions. The method is similar to the above-mentioned operation for removing unnecessary ions remaining on the low mass side. By setting the duty ratio of the square wave RF voltage so that the upper limit mass is slightly higher than the mass-to-charge ratio of the target precursor ion, unnecessary ions remaining on the side higher than the mass-to-charge ratio of the precursor ion can be removed. can be eliminated.
In the manner described above, ions having a very narrow mass-to-charge ratio range centered around the mass-to-charge ratio of the target ions can be efficiently left in the internal space of the ion trap 18.

<Step S6: Ion dissociation step>
After the precursor selection, a predetermined inert gas is supplied into the ion trap 18 from the gas supply section 2 as a collision gas in order to dissociate the precursor ions left in the ion trap 18 . Immediately thereafter, the auxiliary voltage generator 4 applies an excitation voltage having a frequency equal to the secular frequency determined by the mass-to-charge ratio of the precursor ions to the end cap electrodes 182 and 184. As a result, the precursor ions vibrate and collide with the collision gas with energy, causing them to dissociate and generate various product ions.

<Step S7: Cooling process>
After the ion dissociation operation, in order to reduce and stabilize the trajectory of the generated product ions, an inert gas is introduced from the gas supply section 2 into the ion trap 18 as a cooling gas to cool the product ions.

<Step S8: Mass separation/detection step>
After that, the frequency of the rectangular RF voltage applied to the ring electrode 181 and the frequency of the high frequency signal applied to the end cap electrodes 182 and 184 are scanned as appropriate. As a result, the ions are resonantly excited in order of decreasing mass-to-charge ratio (or vice versa), vibrate greatly, and are ejected to the outside through the ion exit hole 185. The ion detector 19 sequentially detects ions ejected from the ion trap 18, generates and outputs a detection signal according to the amount of ions. The data processing unit 5 receives this detection signal and creates an MS ² spectrum indicating the relationship between mass-to-charge ratio and ion intensity.

In the above procedure, ions generated from the sample 15 by one laser beam irradiation are captured in the ion trap 18, and then precursor selection and ion dissociation are performed, and the resulting product ions are subjected to mass separation and detection. Therefore, the amount of target product ions is not necessarily large enough and the ion strength may be low. Therefore, in such a case, in the MALDI-DITMS according to this embodiment, additional ions can be introduced into the ion trap 18.

[MS ² analysis operation when performing additional ion introduction using conventional equipment]
First, the MS ² analysis operation when performing additional ion introduction in the conventional apparatus disclosed in Patent Document 1 and the like will be explained along the flowchart shown in FIG. 3. In FIG. 3, steps that perform substantially the same processing or operations as those shown in FIG. 2 are given the same step numbers.

Steps S1 to S4 are the same as those in FIG. 2, and thereby ions derived from the sample are captured in the internal space of the ion trap 18. Next, with the ions trapped in the internal space of the ion trap 18, the sample 15 is again irradiated with a laser beam for a short time to generate ions (step S13), and the generated ions are passed through the ion entrance hole 183 to the ion trap 18. (step S14). Then, the additionally introduced ions are captured and the captured ions are cooled (steps S15 and S16).

FIG. 7 is a diagram showing waveform diagrams and operations of main parts during additional ion introduction. While target ions are being stably captured in the internal space by applying a rectangular wave RF voltage having a frequency of f1 as a capture voltage to the ring electrode 181, the control unit 6 controls the laser irradiation unit 12 to set a short time width to the target ions. sends a laser driving pulse. The laser irradiation unit 12 emits a laser beam for a short time in response to this drive pulse, and ions are generated from the sample 15. The generation time of the ions is so short that it can be considered that the ions are generated simultaneously. The generated ions are drawn upward from near the sample plate 14, have their trajectory bent by the quadrupole deflector 17, and advance toward the ion injection hole 183.

The control unit 6 controls the main voltage generation unit to change the frequency of the rectangular wave RF voltage to f2, which is higher (for example, four times) than f1, when a predetermined delay time t1 has elapsed after outputting the laser drive pulse. Control 3. At this time, the amplitude is constant. The delay time t1 may be determined to a value corresponding to the travel time for the packet-shaped ions leaving the vicinity of the sample plate 14 to reach the ion injection hole 183. The switching of the frequency of the rectangular wave RF voltage is instantaneously performed as shown in FIG. As the frequency of the square wave RF voltage increases, the pseudo -potential well in the interior space becomes shallower. Therefore, the ions that have reached the ion injection hole 183 enter the ion trap 18 without being bounced back. On the other hand, since the pseudo- potential well has become shallower, the restraining force on the ions is weakened, but the time t2 during which the frequency is maintained at f2 is set shorter than the time during which the ions disappear due to divergence. When the time t2 has elapsed, the frequency of the rectangular wave RF voltage is immediately returned to the original f1. Therefore, ions that were about to diverge from the internal space are pulled back by the electric field, and newly incoming ions are also captured in the internal space, so the amount of ions increases.

After increasing the amount of ions trapped in the internal space of the ion trap 18 as described above, it is possible to carry out MS ² analysis by performing the operations in steps S5 to S8 similar to those in FIG. can. In the method described above, when trying to introduce additional ions into the ion trap 18 in step S14, since there are a large amount of ions already trapped in the ion trap 18, new ions are introduced due to the space charge effect of the ions. There is a problem that it is difficult for ions to enter the ion trap 18. The MS ² analysis operation when performing additional ion introduction in the MALDI-DITMS of this embodiment that solves this problem will be explained along the flowchart shown in FIG. 4. In FIG. 4, steps that perform substantially the same processes or operations as those shown in FIGS. 2 and 3 are given the same step numbers.

As can be seen by comparing FIG. 3 and FIG. 4, in this flowchart, before the operations for additional ion introduction in steps S13 to S16, a precursor selection step (step S11) and a cooling step are performed as an additional ion introduction preparation step. (Step S12) is added.

That is, through the operations in steps S1 to S4, ions originating from the sample are captured in the internal space of the ion trap 18, and the ions are sufficiently cooled. Thereafter, by performing a precursor selection process similar to step S5, only target ions having a predetermined mass-to-charge ratio are left in the internal space of the ion trap 18, and other unnecessary ions are excluded from the internal space. As the precursor selection method, the method described above can be used, but the method is not limited thereto. After performing precursor selection, a cooling gas is introduced into the ion trap 18 to sufficiently cool the remaining target ions. After that, ions newly generated from the sample 15 are additionally introduced into the ion trap 18 by the operations in steps S13 to S16 described above.

In the conventional method described above, ions are additionally introduced into the internal space of the ion trap 18 while various ions derived from the sample are trapped. In contrast, in this method, ions are additionally introduced into the internal space of the ion trap 18 while only the target ions among various ions derived from the sample are captured. Usually, the amount of target ions to be dissociated is considerably smaller than the amount of various ions derived from the sample. In particular, in a MALDI ion source, relatively many matrix-derived ions are generated, and these ions are often trapped in the internal space of the ion trap 18. In that case, many of the ions initially captured in the ion trap 18 are unnecessary for analysis, and the space charge effect of the unnecessary ions makes it difficult to introduce additional ions. According to this method, these unnecessary ions are removed prior to additional ion introduction, and the amount of trapped ions is reduced, so additional ions can be introduced efficiently without being affected by the space charge effect. Thereby, the amount of target ions can be increased efficiently.

Although FIG. 4 shows an example in which ions are additionally introduced into the ion trap 18 only once, ions can be additionally introduced into the ion trap 18 any number of times by repeating steps S11 to S16. Can be done. In this way, by additionally introducing ions into the ion trap 18 one or more times, the amount of target ions having a predetermined mass-to-charge ratio captured in the internal space of the ion trap 18 is increased, and then the step By performing the operations S5 to S8, product ions generated by dissociating target ions with high signal intensity can be detected. As a result, an MS ² (product ion) spectrum of good quality can be obtained.

Next, a modification of the above-described additional ion introduction method will be described with reference to the flowchart shown in FIG. In the above method, when newly generated ions are introduced into the internal space of the ion trap 18, the square wave RF voltage applied to the ring electrode 181 is returned to the normal ion trapping state, and the ions that were previously trapped are returned to the normal ion trapping state. Both ions and newly introduced ions are captured. Therefore, regarding the newly introduced ions, various ions originating from the sample 15 are once captured. In contrast, in the additional ion introduction method according to this modification, after the ions generated in the ion generation step (step S13) are introduced into the internal space of the ion trap 18, they are immediately converted into precursors without returning to the normal ion trapping state. Sorting is performed (step S17).

That is, by changing the duty ratio of the rectangular wave RF voltage applied to the ring electrode 181, for example, a rough separation operation by DAWI can be performed without capturing unnecessary ions outside a predetermined mass-to-charge ratio range that includes the target ions. Eliminate immediately. Of course, the coarse separation operation may be followed by a separation operation that leaves only a narrower mass-to-charge ratio range containing the target ions in the ion trap 18. Furthermore, other than DAWI, such as resonance excitation ejection, may be used to eject ions other than the target ions without capturing them. After leaving only the target ions in the ion trap 18 in this way, the ions may be captured once and the subsequent operations may be performed. According to this method, even when additional ion introduction is performed multiple times, there is no need to once capture all newly introduced ions and then perform precursor selection, so the process can be further shortened.

Of course, the operation of selecting precursors without going through the ion trapping process immediately after introducing ions into the ion trap 18, as described above, is performed when ions are first introduced into the ion trap 18, that is, steps S1 to S4. , S11 can also be used.

[Modified example]
In the MALDI-DITMS of the above embodiment, when additional ions are introduced into the ion trap 18, the frequency of the rectangular wave RF voltage is increased and the pseudo- potential well in the internal space of the ion trap 18 is made shallow. Thereby, the ions that have reached the ion injection hole 183 enter the ion trap 18 without being bounced back by the electric field. As already mentioned, as another method for making it easier for ions to enter the ion trap 18 from the outside, there is a method described in Patent Document 5. Also in the MALDI-DITMS of the above embodiment, the method described in Patent Document 5 can be used when additionally introducing ions.

That is, the ions trapped in the ion trap 18 move according to fluctuations in the trapping electric field, and the ion cloud, which is a collection of ions, alternates between a contracted state near the center of the internal space and a state expanded around it. It fluctuates as if repeating. For example, even if an attempt is made to introduce ions into the ion trap 18 from the ion injection hole 183 at a time when the ion cloud is about to change from a contracted state to an expanded state, the trapping electric field acts to repel the incoming ions. Therefore, ions are difficult to introduce. On the other hand, if ions are introduced at the timing when the ion cloud is about to change from an expanded state to a contracted state, the trapping electric field acts to pull the incident ions into the interior, so that the ions are easily introduced. Therefore, by sending ions in the form of a packet to the ion injection hole 183 at such timing, the ions are efficiently taken into the ion trap 18.

FIG. 8 shows the waveform of the rectangular RF voltage applied to the ring electrode 181 during ion trapping.
When the target ions to be analyzed are positive ions, the suitable timing for introducing the ions into the ion trap 181 is during the low level period of the rectangular wave RF voltage, as shown by T1 in FIG. The latter half of the level period (T1' period in FIG. 8), that is, the phase period of (3/2)π to 2π in one cycle of the symmetrical rectangular RF voltage. However, it takes a certain amount of time (travel time) for the ions generated by laser beam irradiation to pass through the quadrupole deflector 17 and reach the vicinity of the ion entrance hole 183. Therefore, this travel time is determined in advance by simulation calculation or experimentally and stored in the control program storage section 60.

Then, the control unit 6 drives the laser irradiation unit 12 so that ions are generated at a time point that is the travel time back from the starting point of the T1' period (or T1 period) in the rectangular wave RF voltage. Thereby, when the ions generated from the sample 15 by the laser beam irradiation reach the vicinity of the ion injection hole 183, the rectangular wave RF voltage applied to the ring electrode 1181 is in the T1' period (or T1 period). It can be done. As a result, ions are efficiently introduced into the ion trap 18 through the ion injection hole 183.

Further, when the target ions to be analyzed are negative ions, the suitable timing for introducing the ions into the ion trap 18 is the high level period of the rectangular wave RF voltage as shown by T3 in FIG. is the second half of the high level period (T3' period in FIG. 8), that is, the phase period of (1/2)π to π in one cycle of the symmetrical square wave RF voltage. Therefore, the control unit 6 may change the reference position within one cycle of the rectangular wave RF voltage for determining the position (time) at which the laser beam is emitted, depending on the polarity of the ions to be analyzed.

Note that, as described in Patent Document 5, by making the rectangular wave RF voltage an asymmetrical rectangular wave RF voltage with a duty ratio other than 0.5, the time width of the low level or high level is lengthened, and the ion trap 18 The range of mass-to-charge ratios of ions introduced may be widened.

Note that although the above embodiments and modified examples apply the present invention to MALDI-DITMS, it goes without saying that the present invention can also be applied to an ion trap time-of-flight mass spectrometer. In addition, the ion source is not limited to a MALDI ion source, but can also be an ion source that uses an atmospheric pressure ionization method such as an electrospray ionization method, by temporarily accumulating ions at the downstream stage of the ion source and forming them into a packet. The present invention can be applied by arranging a linear type ion trap or the like that emits ions. Furthermore, the ion trap in the present invention may be a linear ion trap instead of a three-dimensional quadrupole ion trap.

Furthermore, the above-described embodiments and modifications are merely examples of the present invention, and it goes without saying that modifications, additions, and modifications may be made as appropriate within the scope of the spirit of the present invention and still fall within the scope of the claims of the present application.

[Various aspects]
It will be appreciated by those skilled in the art that the exemplary embodiments described above are specific examples of the following aspects.

(Section 1) One aspect of the method for introducing ions into an ion trap according to the present invention is an ion trap that traps ions in an internal space by the action of an electric field formed in an internal space surrounded by a plurality of electrodes. A method of introducing ions from the outside,
While ions are captured in the internal space of the ion trap, target ions having a predetermined mass-to-charge ratio or a group of target ions whose mass-to-charge ratio falls within a predetermined mass-to-charge ratio range are left in the internal space, and other an ion selection step of ejecting ions from the interior space;
After performing the ion selection step, temporarily lowering the pseudopotential for trapping ions in the internal space, and introducing new ions from the outside into the internal space while maintaining the trapped ions. or an additional ion introduction step of increasing the amount of trapped ions by introducing new ions from the outside into the internal space at a predetermined timing according to the movement of the trapped ions;
It is intended to carry out the following.

(Section 3) Furthermore, one aspect of the ion trap mass spectrometer according to the present invention is
an ion trap that traps ions in an internal space surrounded by a plurality of electrodes by the action of an electric field formed in the internal space;
a voltage generator that applies a predetermined voltage to each of the plurality of electrodes;
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. Changing the voltage applied to at least one of the plurality of electrodes so as to leave a group of target ions within the mass-to-charge ratio range in the internal space and eject other ions from the internal space, and then changing the voltage applied to at least one of the plurality of electrodes. At least one of the plurality of electrodes is configured to temporarily lower the pseudopotential for trapping ions in the internal space, and introduce new ions from the outside into the ion trap while maintaining the trapped ions. a control unit that changes the voltage applied to one;
It is equipped with the following.

(Section 8) Other aspects of the ion trap mass spectrometer according to the present invention include:
an ion supply unit that supplies ions in a pulsed manner;
an ion trap that traps ions in an internal space surrounded by a plurality of electrodes by the action of an electric field formed in the internal space;
a voltage generator that applies a predetermined voltage to each of the plurality of electrodes;
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. Changing the voltage applied to at least one of the plurality of electrodes so as to leave a group of target ions within the mass-to-charge ratio range in the internal space and eject other ions from the internal space, and then capturing the target ions. a control unit that controls the timing of pulsed ion supply in the ion supply unit so as to introduce new ions from the outside into the internal space at a predetermined timing according to the movement of the ions being moved;
It is equipped with the following.

(Section 10) Furthermore, one aspect of the ion trap mass spectrometry program according to the present invention is an ion trap that traps ions in an internal space by the action of an electric field formed in an internal space surrounded by a plurality of electrodes. , a voltage generating unit that applies a predetermined voltage to each of the plurality of electrodes, and a computer program for driving an ion trap mass spectrometer, the computer program including:
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. The voltage generating section changes the voltage applied to at least one of the plurality of electrodes so that a group of target ions falling within a mass-to-charge ratio range is left in the internal space and other ions are ejected from the internal space. an ion selection step to control the
After performing the ion selection step, the pseudopotential for trapping ions in the internal space is temporarily lowered, and new ions are introduced from the outside into the ion trap while maintaining the trapped ions. an additional ion introduction step of changing the voltage applied to at least one of the plurality of electrodes,
This is what allows you to execute the following.

(Section 11) Another aspect of the ion trap mass spectrometry program according to the present invention is an ion supply unit that supplies ions in a pulsed manner, and an action of an electric field formed in an internal space surrounded by a plurality of electrodes. A computer program for driving an ion trap mass spectrometer comprising an ion trap that traps ions in the internal space and a voltage generator that applies a predetermined voltage to each of the plurality of electrodes. , to the computer,
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. The voltage generating section changes the voltage applied to at least one of the plurality of electrodes so that a group of target ions falling within a mass-to-charge ratio range is left in the internal space and other ions are ejected from the internal space. an ion selection step to control the
After performing the ion selection step, a pulse-like signal is sent from the ion supply unit to introduce new ions into the internal space at a predetermined timing according to the movement of the ions trapped in the ion trap. an additional ion introduction step for supplying ions;
This is what allows you to execute the following.

According to the method for introducing ions into an ion trap described in Section 1, the ion trap mass spectrometer described in Sections 3 and 8, and the ion trap mass spectrometry program described in Sections 10 and 11. For example, when new ions are additionally introduced into the ion trap, only target ions or a group of target ions are accumulated in the internal space of the ion trap, and unnecessary ions have already been removed. Therefore, when trying to introduce new ions into the ion trap, the amount of ions trapped in the ion trap is smaller than in conventional devices, and the space charge effect caused by the trapped ions is also small. . As a result, the efficiency of additionally introducing ions into the ion trap improves, and the ion dissociation operation can be performed with more precursor ions trapped in the internal space of the ion trap. Thereby, the amount of ions subjected to MS ⁿ analysis can be efficiently increased, and the detection sensitivity of product ions can be improved. Furthermore, since the quality of the signal obtained in one mass spectrometry (product ion scan measurement) can be improved, the measurement time can be shortened and the measurement throughput can be further improved.

(Section 2) In the method for introducing ions into the ion trap described in Section 1, in the additional ion introduction step, the pseudopotential is temporarily lowered, and new ions are introduced from the outside while maintaining the trapped ions. After introducing ions into the internal space, the electric field within the ion trap may be returned to a condition where only the target ion or group of target ions can be captured.

(Section 4) In the ion trap mass spectrometer according to Item 3, the control section temporarily lowers the pseudopotential and allows new ions to be added from the outside while maintaining the trapped ions. After the ion is introduced into the internal space, the voltage generator may be controlled so that an RF voltage capable of capturing only the target ion or the target ion group is applied to at least one of the plurality of electrodes. .

In the method for introducing ions into an ion trap described in Section 2 and in the ion trap mass spectrometer described in Section 4, as soon as new ions are introduced into the ion trap, only the target ion or target ion group is detected. An electric field is created within the ion trap that can be trapped. Therefore, among the introduced ions, ions other than the target ion or target ion group are not captured in the internal space of the ion trap, but are ejected to the outside or collide with the electrodes to be eliminated. This makes it possible to omit the step of once trapping unnecessary ions in the ion trap, so that a sufficient amount of target ions or target ion groups can be accumulated in the internal space of the ion trap and ion dissociated in a shorter time. can be analyzed.

(Section 5) In the ion trap mass spectrometer according to Item 3 or 4, the voltage generation section includes a plurality of electrodes forming the ion trap in order to trap ions in the internal space of the ion trap. A rectangular wave RF voltage may be applied to at least one of the.

That is, in the ion trap mass spectrometer described in Section 5, the ion trap is a so-called digital ion trap. According to the ion trap mass spectrometer described in item 5, the conditions for capturing and excluding ions can be changed by changing the frequency and duty ratio of the rectangular wave RF voltage, which can be changed almost instantly. Thereby, various operations on ions can be smoothly performed while suppressing ion loss, and, for example, MS ⁿ analysis with high mass resolution and high sensitivity can be performed.

(Section 6) In the ion trap mass spectrometer according to Item 5, the control unit temporarily lowers the frequency while keeping the amplitude of the rectangular wave RF voltage constant when temporarily lowering the pseudopotential . The voltage generator can be controlled to increase the voltage to .

According to the ion trap mass spectrometer described in Section 6, the frequency of the square wave RF voltage can be changed instantaneously, so that ions can be efficiently ionized while suppressing the dissipation of ions trapped in the internal space of the ion trap. can be additionally introduced.

(Section 7) Furthermore, in the ion trap mass spectrometer according to Item 5 or 6, the control unit may cause ions having a predetermined mass-to-charge ratio or a mass-to-charge ratio to fall within a predetermined mass-to-charge ratio range. When leaving ions in the internal space, the voltage generator can be controlled to keep the frequency of the rectangular wave RF voltage constant and change the duty ratio.

According to the ion trap mass spectrometer described in Section 7, since the duty ratio of the square wave RF voltage can be changed instantaneously, unnecessary ions can be efficiently and quickly removed while suppressing the dissipation of target ions or target ion groups. can be excluded.

(Section 9) Furthermore, in the ion trap mass spectrometer according to Item 8, the voltage generating section is configured to provide at least one of the plurality of electrodes constituting the ion trap in order to trap ions in the internal space of the ion trap. One of them is to apply a rectangular wave RF voltage, and the control unit controls the ion trap at a timing when the ions trapped in the ion trap move from the outer periphery of the trapping region to the center. The timing of pulsed ion supply in the ion supply section can be controlled so that ions are incident on the trap.

Specifically, in the ion trap mass spectrometer described in item 9, depending on the polarity of the ions to be captured, the rectangular wave RF voltage may be used during either the high level period or the low level period, or further within that period. The timing of pulsed ion supply in the ion supply unit may be controlled so that ions are introduced into the ion trap during a certain period. Thereby, additional ions can be efficiently introduced into the ion trap without changing the frequency of the rectangular RF voltage.

1...Measurement part 10...Chamber 100...Window 11...Vacuum pump 12...Laser irradiation part 13...Sample stage 14...Sample plate 15...Sample 16...Extraction electrode 17...Quadrupole type deflector 18...Ion trap 181...Ring electrode 182 ...Entrance side end cap electrode 183...Ion entrance hole 184...Exit side end cap electrode 185...Ion exit hole 19...Ion detector 2...Gas supply section 3...Main voltage generation section 4...Auxiliary voltage generation section 5...Data processing section 6...Control section 60...Control program storage section 7...Input section 8...Display section

Claims (10)

A method for introducing ions from the outside into an ion trap that traps ions in an internal space by the action of an electric field formed in an internal space surrounded by a plurality of electrodes, the method comprising:
While ions are captured in the internal space of the ion trap, target ions having a predetermined mass-to-charge ratio or a group of target ions whose mass-to-charge ratio falls within a predetermined mass-to-charge ratio range are left in the internal space, and other an ion selection step of ejecting ions from the interior space;
After performing the ion selection step, the pseudo-potential for trapping ions in the internal space is temporarily lowered and the trapping is performed without performing a cleavage operation on the target ion or group of target ions being trapped. By newly introducing the target ions or ions containing the target ion group into the internal space from the outside while maintaining the target ions or the target ion group , or by introducing the target ions or the target ions that have been captured By newly introducing the target ion or ions containing the target ion group into the internal space from the outside at a predetermined timing according to the movement of the ion group , the amount of the target ion or target ion group to be captured can be reduced. an additional step of introducing ions to increase the
A method of introducing ions into an ion trap. In the additional ion introduction step, the pseudopotential is temporarily lowered, and while maintaining the captured target ions or target ion groups, new target ions or ions containing the target ion groups are introduced into the interior from the outside. 2. The method of introducing ions into an ion trap according to claim 1, further comprising returning an electric field in the ion trap to a condition where only the target ions or the target ion group can be captured after the ions are introduced into the space. an ion trap that traps ions in an internal space surrounded by a plurality of electrodes by the action of an electric field formed in the internal space;
a voltage generator that applies a predetermined voltage to each of the plurality of electrodes;
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. Changing the voltage applied to at least one of the plurality of electrodes so as to leave a group of target ions within the mass-to-charge ratio range in the internal space and eject other ions from the internal space, and then capturing the target ions. Temporarily lowering the pseudopotential for trapping ions in the internal space without performing a cleavage operation on the target ions or group of target ions being trapped , a control unit that changes the voltage applied to at least one of the plurality of electrodes so as to newly introduce the target ion or ions including the target ion group from the outside into the ion trap while maintaining the target ion;
An ion trap mass spectrometer comprising: The control unit temporarily lowers the pseudopotential, and while maintaining the captured target ions or the target ion group, newly introduces ions including the target ions or the target ion group from the outside into the internal space. 4. The ion trap according to claim 3, wherein after the introduction, the voltage generating unit is controlled so that an RF voltage capable of capturing only the target ion or the target ion group is applied to at least one of the plurality of electrodes. Mass spectrometer. 5. The voltage generator according to claim 3, wherein the voltage generator applies a rectangular RF voltage to at least one of a plurality of electrodes constituting the ion trap in order to trap ions in the internal space of the ion trap. The ion trap mass spectrometer described. The control unit controls the voltage generation unit to temporarily increase the frequency while keeping the amplitude of the rectangular wave RF voltage constant when temporarily lowering the pseudo potential. Ion trap mass spectrometer. The control unit controls the duty while keeping the frequency of the rectangular wave RF voltage constant when leaving target ions having a predetermined mass-to-charge ratio or a group of target ions whose mass-to-charge ratio falls within a predetermined mass-to-charge ratio range in the internal space. The ion trap mass spectrometer according to claim 5 or 6, wherein the voltage generator is controlled to change the ratio. an ion supply unit that supplies ions in a pulsed manner;
an ion trap that traps ions in an internal space surrounded by a plurality of electrodes by the action of an electric field formed in the internal space;
a voltage generator that applies a predetermined voltage to each of the plurality of electrodes;
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. Changing the voltage applied to at least one of the plurality of electrodes so as to leave a group of target ions within the mass-to-charge ratio range in the internal space and eject other ions from the internal space, and then capturing the target ions. Without performing a cleavage operation on the target ions or the target ion group, new target ions or target ions are added from the outside at a predetermined timing according to the movement of the captured target ions or the target ion group. a control unit that controls timing of pulsed ion supply in the ion supply unit so as to introduce ions including the target ion group into the internal space;
An ion trap mass spectrometer comprising: The voltage generating section applies a rectangular wave RF voltage to at least one of the plurality of electrodes constituting the ion trap in order to trap ions in the internal space of the ion trap, and the control section The pulsed ion supply in the ion supply unit is configured such that the ions captured in the ion trap are incident on the ion trap at a timing when the ions are spread from the outer periphery of the trapping region to the center. The ion trap mass spectrometer according to claim 8, wherein the ion trap mass spectrometer controls timing. An ion trap that traps ions in an internal space surrounded by a plurality of electrodes by the action of an electric field formed in the internal space, and a voltage generator that applies a predetermined voltage to each of the plurality of electrodes. A computer program for driving an ion trap mass spectrometer, the computer program comprising:
In a state in which ions are captured in the internal space by applying an RF voltage to at least one of the plurality of electrodes by the voltage generating section, target ions having a predetermined mass-to-charge ratio or mass-to-charge ratios are captured in a predetermined state. The voltage generating section changes the voltage applied to at least one of the plurality of electrodes so that a group of target ions falling within a mass-to-charge ratio range is left in the internal space and other ions are ejected from the internal space. an ion selection step to control the
After performing the ion selection step, the pseudo-potential for trapping ions in the internal space is temporarily lowered without performing a cleavage operation on the target ions being trapped or the group of target ions. applying an electric current to at least one of the plurality of electrodes so as to maintain the target ion or target ion group while newly introducing the target ion or ion containing the target ion group into the ion trap from the outside; an additional ion introduction step that changes the voltage;
A program for ion trap mass spectrometry that runs.

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