Driving method for quadrupole mass filter and quadrupole type mass spectroscope

Abstract

To enhance ion permeation efficiency in a quadrupole mass filter.SOLUTION: A quadrupole type mass spectroscope comprises: a quadrupole mass filter (50) consisting of a main rod part (500) including rod electrodes disposed so as to enclose a central axis C and a first pre-rod part (501) including rod electrodes disposed in front; a main voltage application section (7) for applying to the main rod part a voltage obtained by superposing a DC voltage and a RF voltage corresponding to m / z of ions; and an auxiliary voltage application section (7) for applying to the first pre-rod part a voltage obtained by superposing, a RF voltage in the same frequency as the RF voltage and a DC voltage different from the DC voltage applied to the main rod part. A direction in which centers of a pair of rod electrodes opposed in a plane orthogonal to the central axis C are connected is defined as an X axis direction and a direction in which centers of the other pair of rod electrodes are connected is defined as a Y axis direction. A voltage in the auxiliary voltage application section is set in such a manner that a parameter relating to perennial vibration of ions in the X and Y directions substantially satisfies a specific condition.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a quadrupole mass spectrometer that uses a quadrupole mass filter as a mass separator, and a method for driving the quadrupole mass filter. In this specification, the term "quadrupole mass spectrometer" includes not only single-type quadrupole mass spectrometers, but also triple quadrupole mass spectrometers in which quadrupole mass filters are arranged before and after a collision cell, and quadrupole-time-of-flight mass spectrometers in which a quadrupole mass filter is arranged before a collision cell and a time-of-flight mass analyzer is arranged after the collision cell. [Background technology]

[0002] In a single-type quadrupole mass spectrometer, ions derived from components (compounds) contained in a sample are separated by a quadrupole mass filter according to their mass-to-charge ratio (strictly speaking, this is the italicized "m / z", but in this specification it is referred to as "mass-to-charge ratio" or "m / z"), and the separated ions are detected by an ion detector. By repeatedly performing mass scanning over a predetermined m / z range in the quadrupole mass filter, it is possible to repeatedly obtain a mass spectrum showing the relationship between m / z and ion intensity.

[0003] A quadrupole mass filter generally has a configuration in which four rod electrodes, each having a cylindrical outer shape, are arranged parallel to each other so as to be in contact with the outside of an inscribed circle of a predetermined radius centered on a linear axis, and spaced apart at equal angular intervals (90°) in the circumferential direction. A voltage +(U+Vcosωt) obtained by superimposing a radio frequency voltage (RF voltage) Vcosωt on a DC voltage U is applied to two rod electrodes facing each other across the central axis, which is also the ion optical axis, and a voltage -(U+Vcosωt) obtained by superimposing a DC voltage -U with an inverted polarity and an RF voltage -Vcosωt with an inverted phase is applied to the other two rod electrodes. By setting the voltage value U of this DC voltage and the amplitude value V of the RF voltage to values ​​corresponding to the m / z while maintaining a predetermined relationship, ions having that m / z can be selectively passed.

[0004] Disturbances in the electric field occur near the end of the rod electrode, and these disturbances are one of the factors that reduce the ion transmittance. Therefore, in order to reduce such disturbances in the edge electric field, a pre-rod section is often provided in front of the main rod section, which is made of a rod electrode having an ion-selective function. In general, the pre-rod electrode constituting the pre-rod section has the same diameter as the main rod electrode and is a cylindrical rod electrode with a short outer diameter in the ion optical axis direction. Since the pre-rod section needs to focus ions with a wide range of m / z, a DC voltage U is generally not applied to the pre-rod electrode, but an RF voltage with the same frequency and smaller amplitude as the RF voltage applied to the main rod electrode is applied. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] U.S. Patent No. 8,207,495 [Non-patent literature]

[0006] [Non-Patent Document 1] Shin Fujita, "Elucidation of ion motion in quadrupole mass spectrometer by Bloch function", International Journal of Modern Physics A, Vol. 34, No. 36, 2019 Summary of the Invention [Problem to be solved by the invention]

[0007] In order to further improve the ion transmission rate in a quadrupole mass spectrometer, the device described in Patent Document 1 applies a DC bias voltage to the pre-rod electrode in addition to an RF voltage of the same frequency as that of the main rod electrode, and changes the voltage value according to the m / z of the ion to control the oscillation frequency of the ion passing through the pre-rod electrode. This technology improves the ion transmission efficiency and improves detection sensitivity compared to the case where the DC bias voltage is constant, regardless of the m / z of the ion.

[0008] On the other hand, one of the present inventors has reported in Non-Patent Document 1 an attempt to theoretically analyze the behavior of ions passing through a quadrupole mass filter using complex amplitudes and the like. Here, it is shown that when ions are transferred from the auxiliary electric field formed by the pre-rod section to which only an RF voltage is applied to the main electric field formed by the main rod section, only a portion of the ions accepted by the auxiliary electric field can be appropriately transferred to the next main electric field. In other words, this means that many ions are lost when ions are transferred from the pre-rod section to the main rod section. Therefore, in order to improve the ion transmission efficiency in the quadrupole mass filter, it is important to improve the efficiency of ion transfer from the pre-rod section to the main rod section. However, Non-Patent Document 1 does not propose a specific method for improving the efficiency of ion transfer from the pre-rod section to the main rod section.

[0009] Although the method described in the above-mentioned Patent Document 1 is one method for improving ion permeation efficiency, the inventors' investigations have revealed that the effect of the improvement is not necessarily satisfactory, and further improvement is desired.

[0010] The present invention has been made to solve these problems, and has as its main object to improve the analytical sensitivity in a quadrupole mass spectrometer by further improving the overall ion transmission efficiency in a quadrupole mass filter. [Means for solving the problem]

[0011] One aspect of a method for driving a quadrupole mass filter according to the present invention is a method for operating a quadrupole mass filter comprising a main rod section including four rod electrodes arranged to surround a central axis, and a first pre-rod section including four rod electrodes arranged at a position upstream of the main rod section in the extension direction of the central axis, the method comprising: a voltage calculation step of determining DC voltage Up and RF voltage amplitude Vp (where the relationship between Up, Vp, a, and q is defined by the following equations (3) and (4)) such that, when a direction connecting the centers of a pair of rod electrodes facing each other across the central axis in a plane perpendicular to the central axis is defined as the X-axis direction, and a direction connecting the centers of another pair of rod electrodes is defined as the Y-axis direction, and β values ​​(0<β<1) related to the secular oscillation of ions in each of the X and Y directions are defined as βx and βy, respectively, the a-values ​​and q-values ​​which are parameters of the Mathieu equation expressing ion motion and have the relationship between βx and βy and the following equations (1) and (2), a≠0, (π-βx·π)N={(1 / 2)+m}π, and βy·π·N={(1 / 2)+n}π, (where m, n, and N are natural numbers); a voltage application step of applying, during analysis, a voltage obtained by superimposing a DC voltage corresponding to the m / z of a target ion and an RF voltage corresponding to the m / z to each rod electrode of the main rod section, and applying, to each rod electrode of the first pre-rod section, a voltage obtained by superimposing an RF voltage ±Vp cosωt having the same frequency and amplitude as the RF voltage applied to the main rod section and a DC voltage ±Up having a different voltage value from the DC voltage applied to the main rod section; has.

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[0012] Furthermore, one aspect of the quadrupole mass spectrometer according to the present invention is a quadrupole mass filter including a main rod section including four rod electrodes arranged to surround a central axis, and a first pre-rod section including four rod electrodes arranged to surround the central axis at a position upstream of the main rod section along the central axis in the ion flow; a main voltage application unit that applies a voltage obtained by superposing a DC voltage corresponding to the m / z of an ion and an RF voltage corresponding to the m / z to each rod electrode of the main rod unit in order to form a quadrupole electric field in the main rod unit; an auxiliary voltage application unit that applies a voltage obtained by superimposing an RF voltage having the same frequency as the RF voltage and a DC voltage having a different voltage value from the DC voltage applied to the main rod section to each rod electrode of the first pre-rod section in order to form a quadrupole electric field in the first pre-rod section; a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: when a direction connecting the centers of a pair of rod electrodes opposing each other across the central axis in a plane perpendicular to the central axis is defined as an X-axis direction, and a direction connecting the centers of another pair of rod electrodes is defined as a Y-axis direction, and β values ​​(0<β<1) related to the secular oscillation of ions in each of the X and Y directions are defined as βx and βy, the parameters of the Mathieu equation expressing the motion of ions are related to Up and Vp by the above formulas (3) and (4), and βx and βy are related to the above formulas (1) and (2), the values ​​of a and q are a ≠ 0, and (π-βx π)N={(1 / 2)+m}π and βy π π N={(1 / 2)+n}π, (where m, n, and N are natural numbers). Effect of the Invention

[0013] According to the above aspect of the present invention, the loss of ions that pass through the pre-rod section when they enter the main rod section is reduced more than ever before, thereby improving the overall ion transmission efficiency in the quadrupole mass filter, thereby increasing the amount of ions sent to devices downstream of the quadrupole mass filter, such as an ion detector or a collision cell, and improving analytical sensitivity. [Brief description of the drawings]

[0014] [Figure 1] 1 is a schematic diagram showing the overall configuration of a mass spectrometer according to an embodiment of the present invention; [Diagram 2] FIG. 2 is a configuration diagram of a pre-quadrupole mass filter in the mass spectrometer of the present embodiment. [Diagram 3] FIG. 3 is a schematic cross-sectional view of the pre-quadrupole mass filter shown in FIG. 2 taken along a plane perpendicular to the central axis. [Figure 4] FIG. 4 is a configuration diagram of a modified example of the pre-quadrupole mass filter in the mass spectrometer of the present embodiment. [Diagram 5] 1 is an acceptance diagram showing an example of the RF voltage period dependence of the position (x) and velocity (dx / dξ) of an ion at a given position in the electric field of a quadrupole mass filter. [Figure 6] A diagram showing the positions of a and q that provide good ion transmission on the Mathieu diagram. [Figure 7] 11A and 11B are diagrams showing ion emittance at each portion when an ion implantation lens is provided. [Figure 8] 1A and 1B are diagrams showing the evaluation results of ion transmission rate and peak shape by simulation. [Figure 9] FIG. 13 is a diagram showing the results of an experimental sensitivity comparison. [Figure 10] FIG. 13 is a graph showing experimental comparison results of peak shapes. [Figure 11] 4 is an acceptance diagram showing the RF voltage period dependence of the position and velocity of ions in the X-axis and Y-axis directions at the inlet of the main rod section in the mass spectrometer of this embodiment. FIG. [Figure 12]1 is an acceptance diagram showing the RF voltage period dependence of the position and velocity of ions in the X-axis and Y-axis directions at the inlet of the main rod section in a conventional mass spectrometer. [Figure 13] FIG. 13 is an acceptance diagram showing the RF voltage period dependence of the ion position and velocity in the X-axis and Y-axis directions at the inlet of the main rod section when the a value is set to 0 and the complex rotation angle per RF voltage period is controlled. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] The quadrupole mass spectrometer according to the present invention can be generally applied to mass spectrometers that use a quadrupole mass filter as a mass separator, and therefore includes a single-type quadrupole mass spectrometer, a triple quadrupole mass spectrometer, a quadrupole time-of-flight mass spectrometer, and the like.

[0016] [Overall configuration and operation of a mass spectrometer according to one embodiment] A triple quadrupole mass spectrometer according to one embodiment of the present invention will now be described with reference to the accompanying drawings. Fig. 1 is a schematic diagram of the overall configuration of a mass spectrometer according to the present embodiment. This mass spectrometer is a triple quadrupole mass spectrometer using an atmospheric pressure ion source, and is generally used as a liquid chromatograph mass spectrometer (LC-MS) in combination with a liquid chromatograph. For convenience of explanation, three axes, X, Y, and Z, which are mutually orthogonal, are defined as shown in Fig. 1.

[0017] This mass spectrometer is equipped with an ionization section 6 having an ionization chamber 60 provided therein, in front of a vacuum chamber 1 (upstream of the flight path of ions). The inside of the vacuum chamber 1 is partitioned into four chambers: a first intermediate vacuum chamber 2, a second intermediate vacuum chamber 3, a third intermediate vacuum chamber 4, and an analysis chamber 5. The ionization chamber 60 is at approximately atmospheric pressure, and each chamber after the first intermediate vacuum chamber 2 is evacuated to a vacuum by a rotary pump and a turbo molecular pump (not shown). As a result, this mass spectrometer is configured as a multi-stage differential pumping system in which the degree of vacuum increases in stages from the ionization chamber 60 to the first intermediate vacuum chamber 2, the second intermediate vacuum chamber 3, the third intermediate vacuum chamber 4, and the analysis chamber 5.

[0018] An electrospray ionization (ESI) probe 61 is disposed in the ionization chamber 60, and the ionization chamber 60 and the first intermediate vacuum chamber 2 communicate with each other through a desolvation tube 62 that is heated to a high temperature. An ion guide 20 called a Q-array is disposed in the first intermediate vacuum chamber 2, and the first intermediate vacuum chamber 2 and the second intermediate vacuum chamber 3 communicate with each other through a small hole provided at the top of the skimmer 21. The second intermediate vacuum chamber 3 and the third intermediate vacuum chamber 4 are each provided with a multipole ion guide 30, 40 made up of a plurality of rod electrodes arranged to surround an ion optical axis (the central axis of the ion flight path) C extending in the Z-axis direction.

[0019] In the analysis chamber 5, along the ion optical axis C, there are arranged a front-stage quadrupole mass filter 50, a collision cell 51 having an internal ion guide 52 that focuses and transports ions, a rear-stage quadrupole mass filter 53, and an ion detector 54 that outputs an ion intensity according to the amount of incident ions as a detection signal.

[0020] A predetermined voltage is applied from the power supply unit 7 to the ESI probe 61, the desolvation tube 62, the ion guides 20, 30, 40, 52, the quadrupole mass filters 50, 53, etc. under the control of the control unit 8. In order to avoid complicating the drawing, some of the wiring for applying voltage is omitted. A detection signal from the ion detector 54 is converted to digital data by an analog-digital converter (not shown) and input to a data processing unit (not shown). In general, the data processing unit and control unit 8 use a general-purpose personal computer as a hardware resource, and at least some of the functions are achieved by executing software (computer programs) installed on the computer.

[0021] A typical analysis operation in the mass spectrometer of this embodiment will now be briefly described. When a sample liquid is introduced into the ESI probe 61, charged sample droplets are sprayed from the tip of the ESI probe 61 into the ionization chamber 60. The charged droplets collide with the surrounding gas and are broken down into fine particles, and in the process of the solvent in the droplets evaporating, the component molecules contained in the sample liquid are ionized. The generated ions are sucked into the desolvation tube 62 together with the charged droplets whose solvent has not yet been fully evaporated, and are sent to the first intermediate vacuum chamber 2. Evaporation of the solvent in the droplets is further promoted in the desolvation tube 62, thereby accelerating the generation of ions derived from the sample components.

[0022] The ions introduced into the first intermediate vacuum chamber 2 are converged near the small hole of the skimmer 21 by the action of the electric field formed by the ion guide 20, and pass through the small hole to enter the second intermediate vacuum chamber 3. The ions are then transported successively while being converged by the action of the electric fields formed by the ion guides 30 and 40, and enter the analysis chamber 5.

[0023] In the analysis chamber 5, ions derived from sample components enter the front quadrupole mass filter 50, and only ions having m / z values ​​corresponding to the voltages applied to the rod electrodes constituting the front quadrupole mass filter 50 pass through the front quadrupole mass filter 50. The ions (precursor ions) that have passed through the front quadrupole mass filter 50 enter the collision cell 51, where they collide with a collision gas introduced into the collision cell 51, causing collision-induced dissociation (CID). Various product ions generated by this CID are focused and transported by the ion guide 52, and enter the rear quadrupole mass filter 53. Of the product ions that have entered, only ions having m / z values ​​corresponding to the voltages applied to the rod electrodes constituting the rear quadrupole mass filter 53 pass through the mass filter 53 and enter the ion detector 54. The ion detector 54 outputs an ion intensity signal whose magnitude corresponds to the amount of the ions that have entered.

[0024] In the above-mentioned mass spectrometer, specific product ions derived from specific component molecules in the sample can be detected by selectively passing ions having predetermined m / z through the front quadrupole mass filter 50 and the rear quadrupole mass filter 53, respectively.

[0025] As shown in Fig. 1, the front-stage quadrupole mass filter 50 is composed of three sections separated from each other along the ion optical axis C. That is, the mass filter 50 includes a central main rod section 500, a pre-rod section 501 arranged in front of it (in the direction in which ions enter), and a post-rod section 502 arranged behind it (in the direction in which ions exit). On the other hand, the rear-stage quadrupole mass filter 53 includes a main rod section 530 and a pre-rod section 531 arranged in front of the main rod section 530. The main rod sections 500 and 530 in each quadrupole mass filter 50 and 53 have the function of selecting ions according to m / z, and the pre-rod sections 501 and 531 and the post-rod section 502 mainly have the function of reducing disturbance of the electric field at the edges of the main rod sections 500 and 503.

[0026] [Quadrupole mass filter configuration] Although the following description will be given taking the pre-quadrupole mass filter 50 as an example, the same applies to the post-quadrupole mass filter 53. The characteristic configuration and operation of the quadrupole mass filter 50 will be described with reference to Figures 2 and 3. Figures 2 and 3 show the configuration of roughly the front half of the front-stage quadrupole mass filter 50, with Figure 2 being an end view in the XZ plane including the ion optical axis C, and Figure 3 being an end view in the XY plane orthogonal to the ion optical axis C.

[0027] The main rod section 500 includes four rod electrodes 5001, 5002, 5003, and 5004 each having a cylindrical outer shape, and the four rod electrodes 5001 to 5004 are arranged parallel to each other so as to be tangent to an inscribed circle of a predetermined radius centered on the ion optical axis C, and at equal angular intervals (90°) in the circumferential direction around the ion optical axis C. Of the four rod electrodes 5001 to 5004, a voltage +(Um+V·cosωt) is applied from the power supply unit 7 under the control of the control unit 8 to two rod electrodes 5001 and 5003 that face each other in the X-axis direction across the ion optical axis C, and a voltage -(Um+V·cosωt) is applied from the power supply unit 7 to two rod electrodes 5002 and 5004 that face each other in the Y-axis direction across the ion optical axis C. Here, Um is a DC voltage for ion selection, Vcosωt is an RF voltage for ion selection, and Um and V have a certain relationship and change according to m / z. A DC bias voltage is commonly applied to each rod electrode, which will be described later. When simply referring to a "DC voltage," it refers to a DC voltage for ion selection, that is, a DC voltage with different polarities between circumferentially adjacent rod electrodes, and is to be distinguished from a DC bias voltage.

[0028] Like the main rod section 500, the pre-rod section (first pre-rod section) 501 also includes four pre-rod electrodes 5011, 5012, 5013, and 5014 each having a cylindrical outer shape. Except for the fact that the axial length of the four pre-rod electrodes 5011-5014 is short, their shapes and arrangements are the same as those of the main rod electrodes 5001-5004 of the main rod section 500. The shapes and arrangements of the rod electrodes of the pre-rod section 501 and the main rod section 500 are similar to those of a quadrupole mass filter in a conventional mass spectrometer.

[0029] Under the control of the control unit 8, a voltage ±(Up+0.8V·cosωt) obtained by superimposing an RF voltage (±Vp·cosωt=±0.8V·cosωt) obtained by multiplying an RF voltage ±V·cosωt by a predetermined constant (0.8 in this example, which is just an example) and a DC voltage ±Up having a voltage value different from the DC voltage ±Um is applied from the power supply unit 7 to each of the pre-rod electrodes 5011-5014 of the pre-rod section 501. That is, generally in the past, an RF voltage corresponding to V·cosωt is applied to the pre-rod electrodes of the pre-rod section, but a DC voltage corresponding to Um is not applied thereto. In contrast, in the mass spectrometer of this embodiment, in addition to the RF voltage Vp·cosωt corresponding to V·cosωt, a DC voltage Up corresponding to Um is also applied to the pre-rod electrodes 5011-5014. By appropriately setting the voltage value (absolute value) of this DC voltage Up, the efficiency of ions leaving the pre-rod section 501 and entering the main rod section 500 can be improved, that is, the ion loss can be reduced, and the overall ion transmittance can be improved.

[0030] The values ​​of the DC voltage Up, the DC voltage Um, the amplitude V (and Vp) of the RF voltage, and the like can be calculated by a computer that substantially constitutes the control unit 8, but may be calculated not by a computer (i.e., a function achieved by executing a program) but by a digital signal processor or the like for calculation. Alternatively, appropriate values ​​calculated by an independent computer that is not connected to the mass spectrometer, rather than a computer connected to the mass spectrometer for controlling the same, may be stored in the memory of the control unit 8, and the control unit 8 may appropriately select the value to control the power supply unit 7. A method for determining the voltage value of the DC voltage Up and specific examples will be described later.

[0031] [Configuration of modified quadrupole mass filter] 2, the pre-rod section 501 is a single stage, but as shown in Fig. 4, the pre-rod section 501 can also be configured as a two-stage structure separated in the direction along the ion optical axis C. In this configuration, a voltage ±(Up+0.95V·cosωt) obtained by superimposing an RF voltage obtained by multiplying an RF voltage ±V·cosωt by a predetermined constant (0.95 in this example, which is just an example) and a DC voltage ±Up, which is a voltage value different from the DC voltage ±Um, is applied from the power supply section 7 to each of the pre-rod electrodes 5011B to 5014B of the second pre-rod section 501B arranged immediately before the main rod section 500. On the other hand, the DC voltages ±Up are not applied to each of the pre-rod electrodes 5011A to 5014A of the first pre-rod section 501A arranged immediately before the second pre-rod section 501A, and an RF voltage obtained by multiplying the RF voltages ±V·cosωt by a predetermined constant (0.8 in this example) is applied from the power supply unit 7.

[0032] Further, a predetermined DC bias voltage VBm is applied to the rod electrode included in the main rod section 500, a predetermined DC bias voltage VB2 is applied to the rod electrode included in the second pre-rod section 501B, and a predetermined DC bias voltage VB1 is applied to the rod electrode included in the first pre-rod section 501A. As described later, the voltage value of the DC bias voltage VB1 and the voltage value of the DC bias voltage VB2 can be appropriately adjusted so that the ion intensity for ions having a target m / z is as high as possible while maintaining a predetermined relationship.

[0033] [Setting the voltage applied to the pre-rod electrode] Generally, the conditions under which ions oscillate stably in the electric field of a quadrupole mass filter are indicated by the stable region in a Mathieu diagram, with the horizontal axis representing the q value and the vertical axis representing the a value, as shown in Figure 6. In Figure 6, the approximately triangular range indicated by the thick line is the stable region, and (a, q) included in this stable region corresponds to the voltage conditions under which ions can exist stably. Although it is well known, the definitions of the a and q values ​​in a quadrupole mass filter are shown again in the following equation (5). a = (8eU) / (mr0 2 ω 2 ),q=(4eV) / (mr0 2 ω 2 ) …(5) Here, m is the mass of the ion, e is the charge of the ion, ω is the angular frequency of the RF voltage, U is the voltage value of the DC voltage, and V is the amplitude value of the RF voltage. From this formula, it can be seen that the a value corresponds to the voltage value of the DC voltage, and the q value corresponds to the amplitude value of the RF voltage.

[0034] In a conventional quadrupole mass spectrometer in which only an RF voltage is applied to the pre-rod electrode, the voltage condition in the pre-rod section is a=0 within the stable region, that is, it is located on the base of the approximately triangular stable region in FIG. 6. According to FIG. 3 of Non-Patent Document 1, when a=0, the ion transmission rate is very high. In other words, in conventional devices, the pre-rod section is driven under voltage conditions that allow ions to pass through efficiently. Despite this, only a portion of the ions transported by the pre-rod section can enter the main rod section.

[0035] In Non-Patent Document 1, as a theoretical analysis method of ion vibration, an attempt is made to express the motion of ions in phase space when passing through the electric field of a quadrupole mass filter by expanding complex coefficients in Bloch functions. Although not described in detail here, this allows the acceptance (or emittance) of ions in a quadrupole mass filter to be drawn on a plane whose horizontal axis is the position x of the ion in phase space and whose vertical axis is the velocity dx / dξ (where ξ is normalized time, ξ=(ω / 2)·t) of the ion in the phase space, as exemplified in FIG. 5 (and FIG. 11, FIG. 12, and FIG. 13 described later). Here, this diagram is called an acceptance diagram. However, the acceptance here is essentially the same as the emittance.

[0036] In the acceptance diagram, the phase space represented by an ellipse surrounding the center point (x=0, dx / dξ=0) corresponds to the trajectory of an ion in one period of the RF voltage. The acceptance (or emittance) is a function of the normalized time ξ, and as the normalized time ξ progresses, the phase space represented by the ellipse rotates to the right as shown by the arrow in Figure 5. The phase space represented by the ellipse also rotates to the right every time the ion advances by one period of the RF voltage. Therefore, the ion exists at a different position in the phase space every period of the RF voltage. Thus, the significant change in the acceptance depending on the phase of the RF voltage is one of the factors that makes it difficult to efficiently inject ions into a quadrupole mass filter.

[0037] In Non-Patent Document 1, a simulation analysis was performed on the emittance conversion of ions by the auxiliary electric field formed in the pre-rod section, and it was shown that when ions are present in the auxiliary electric field for a specific number of periods of the RF voltage, the phase space emittance of the ions in the auxiliary electric field is concentrated in the center. It was shown that this centralization of the phase space emittance of ions occurs when the phase space of an ellipse in an acceptance diagram is oriented in a specific direction, specifically, when an ellipse showing the complex amplitude corresponding to the phase space acceptance is oriented in the vertical direction (imaginary axis direction) on a basic complex amplitude diagram showing the periodic complex amplitude of ions with the horizontal axis as a real number and the vertical axis as an imaginary number.

[0038] When ions move from the pre-rod section to the main rod section, if the phase space emittance of the ions is collected in the center as described above, the ions can be more efficiently accepted by the main rod section. Therefore, the present inventors have considered determining the conditions of the auxiliary electric field to adjust the complex rotation angle for each RF voltage cycle so that an ellipse showing the complex amplitude corresponding to the phase space acceptance in the auxiliary electric field formed by the pre-rod section faces the vertical direction (imaginary axis direction) for a predetermined number of RF voltage cycles.

[0039] According to the study by the inventor, it is possible to control the complex rotation angle for each period of the RF voltage by adjusting the amplitude value Vp of the RF voltage without applying a DC voltage to the pre-rod electrode, that is, while keeping the a value, which is a parameter of the Mathieu equation, at 0. However, the most important factor in determining the ion transmittance is the "state of emittance conversion." In order to match the emittance of the device (e.g., vacuum bulkhead lens or injection lens) located in front of the pre-rod section with the acceptance of the pre-rod section, it is necessary to confirm what (q, a) is optimal based on the emittance. Even if the complex rotation angle is the same, if (q, a) is different, the state of emittance conversion will be different, resulting in a difference in the ion transmittance.

[0040] When the complex rotation angle per RF voltage period is controlled by setting the a value to 0, the conversion of the emittance in the x-axis direction is insufficient, as shown in an example of (q, a) = (0, 0.560) in Figure 13. Therefore, by applying not only the RF voltage but also a DC voltage to the pre-rod electrode and adjusting the voltage value of the DC voltage, that is, by appropriately determining the q value and the a value (a ≠ 0) in the pre-rod section, the complex rotation angle per RF voltage period is controlled so that the ellipse showing the complex amplitude faces the vertical direction (imaginary axis direction) for a predetermined number of RF voltage periods. By setting a ≠ 0 (i.e., superimposing the U voltage), the emittance can be effectively converted in both the x-axis direction and the y-axis direction, as shown in an example of (q, a) = (0.672, 0.166) in Figure 11, and the ion transmission rate can be increased.

[0041] It should be noted here that it is necessary to control the ions so that they are concentrated in the center when they move from the pre-rod section to the main rod section in both the X-axis direction and the Y-axis direction in real space. Such control is difficult to achieve by the method described in Patent Document 1, which controls the number of vibrations of the ions passing through the pre-rod section by the voltage value of the DC bias voltage applied to the pre-rod electrode. Figures 12(A) and 12(B) are acceptance diagrams showing the emittance of ions in the X-axis direction and the Y-axis direction at the outlet end of the pre-rod section according to the method described in Patent Document 1. Here, the DC bias voltage is adjusted so that the emittance in the Y-axis direction is concentrated in the center. As can be seen from the diagram, in this case, in both phases, the ions are concentrated in the center in the Y-axis direction, but are not concentrated in the center in the X-axis direction. Therefore, some of the ions that have left the pre-rod section are not accepted by the main rod section, which is a major factor in the decrease in the transmittance of the ions.

[0042] The condition for making the distribution axis direction of the complex amplitude (direction of the ellipse) coincide with the imaginary axis direction simultaneously in both the X-axis and Y-axis directions by adjusting the RF periodic rotation angle θ can be expressed by the following equation (6). Here, θx is the RF periodic rotation angle in the X-axis direction, and θy is the RF periodic rotation angle in the Y-axis direction. Returning to the motion of ions, these RF periodic rotation angles correspond to the ion oscillation frequencies, and are known as the β values ​​in the Mathieu diagram. In other words, θx and θy correspond to the values ​​obtained by multiplying the secular frequencies βx and βy of the ion oscillation in the X-axis and Y-axis directions by π. (π-θx)·N={(1 / 2)+m}π, θy·N={(1 / 2)+n}π …(6) Here, m, n, and N are all natural numbers, and N is the time that the ions exist in the auxiliary electric field, expressed as the number of periods of the RF voltage.

[0043] The above equation (6) can be rewritten as the following equation (7). θx={1-[(1 / 2)+m] / N}π, θy=[(1 / 2)+n]·π / N …(7) When considering the simplest case of m=n=1, the (θx, θy) obtained from equation (7) are ((4 / 5)π, (1 / 5)π), ((3 / 4)π, (1 / 4)π), ((2 / 3)π, (1 / 3)π), ((1 / 2)π, (1 / 2)π), etc.

[0044] 11(A) and (B) are acceptance diagrams at the inlet of the main rod section 500 when θx=(3 / 4)π and θy=(1 / 4)π. Compared with the acceptance diagram shown in Fig. 12, it can be seen that ions are concentrated in the center in both the X-axis and Y-axis directions.

[0045] By applying to the pre-rod electrode a voltage corresponding to the q value and the a value that satisfy the condition of the above formula (2) or (3), an improvement in ion transmission efficiency can be expected.

[0046] Based on the above theory, a wide range of conditions, including m=n=1, were examined by simulation and experiment to confirm whether the ion permeation efficiency was actually improved and the ionic strength was increased. Simulations confirmed that the signal strength increased compared to the conventional device, where the applied voltage to the pre-rod was set to (q,a)=(0.5648,0), for the conditions (q,a) indicated by black circles, squares, and stars on the Mathieu diagram in Figure 6. In addition, verification was also conducted using an actual device for the conditions (q,a) indicated by squares and stars, and it was confirmed that the signal strength increased compared to the conventional device. The stars correspond to (m,n,N)=(1,1,6), and the squares correspond to (m,n,N)=(2,2,6). Thus, it was confirmed by both simulation and experiment that the ion permeability can be improved by adjusting the voltage value of the DC voltage applied to the pre-rod electrode so that the a and q values ​​satisfy equation (6) or (7). More detailed simulation and experimental results will be described later.

[0047] In principle, there are no constraints on the values ​​of n, m, and N, but in practice there are constraints imposed by various factors. For example, N is the number of periods of the RF voltage, and although N=1 is theoretically possible, the emittance of the ions is corrected (converted) little by little for each period of the RF voltage, so that if the number of periods is small, it is difficult to adequately adjust the deviation in the distribution axis direction of the complex amplitude. On the other hand, if N is too large, it is difficult to adequately control the behavior of the ions with respect to the variation in the angle at which the ions are incident on the pre-rod section. For these reasons, the preferred range of N is 3 to 20, more preferably 4 to 10, and the most preferred among the values ​​examined is N=6. In addition, in order to obtain a good balance between the X-axis direction and the Y-axis direction, it is preferable that n and m are the same or close to each other as much as possible, and the smaller the values, the better. Therefore, for example, (n,m)=(1,1), (1,2), (2,1), (2,2), etc. are preferable.

[0048] [Adjustment of DC bias voltage in two-stage pre-rod section] In the example shown in Fig. 2, the pre-rod section 501 has a single stage configuration, but when a DC voltage is applied to the pre-rod electrodes, there is a risk that the efficiency of ion injection from the previous stage will decrease compared to when no DC voltage is applied. In order to avoid this, the pre-rod section 501 can have a two-stage configuration as shown in Fig. 4. In the example shown in Fig. 4, a DC voltage (±Up) is applied together with an RF voltage (±0.95 V·cosωt in this example) to the pre-rod electrodes 5011A-5014A constituting the first pre-rod section 501A immediately before the main rod section 500, and an RF voltage (±0.8 V·cosωt in this example) is applied to the pre-rod electrodes 5011B-5014B constituting the second pre-rod section 501B further ahead of them, without applying a DC voltage.

[0049] In this case, by setting the length of the rod electrodes of each pre-rod section 501B, 501A, the RF voltage, the DC voltage, and the DC bias voltage to appropriate values, it is possible to simultaneously achieve conditions for efficient ion transport both between the outlet of the second pre-rod section 501B and the inlet of the first pre-rod section 501A, and between the outlet of the first pre-rod section 501A and the inlet of the main rod section 500.

[0050] The above formula (6) is theoretically derived based on the technical idea of ​​increasing the ion transmittance and ion separation ability by aligning the distribution axis direction of the complex amplitude with the imaginary axis direction simultaneously in both the X-axis and Y-axis directions. However, in an actual device, since there are variations (mechanical errors) in the length of the rod electrodes and their relative positions around the central axis for each device, even if a specified voltage based on the design value of the mass spectrometer is applied to each rod electrode, the condition of the above formula (6) is not necessarily completely satisfied. In the present specification, "substantially satisfying" a specific condition means that in such a case, the voltage value is set to an initial value based on the above theoretical formula, and in order to offset mechanical errors and the like to obtain the original effect, parameter adjustment is performed for each device, or even for the same device, at an appropriate timing based on actual performance, such as to maximize the ion intensity.

[0051] In an apparatus having a two-stage pre-rod section 501, for example, the RF voltage and DC voltage applied to each pre-rod section 501B, 501A can be set to design values, and then the DC bias voltage can be adjusted to adjust the parameters. However, if optimization is attempted by individually adjusting the DC bias voltages applied to the second pre-rod section 501B and the first pre-rod section 501A, the adjustment is time-consuming and takes a long time. In contrast, the time required to optimize the DC bias voltage can be shortened by adopting the adjustment method described below.

[0052] That is, in this adjustment method, while keeping the voltage value ratio between the DC bias voltage applied to the second pre-rod section 501B and the DC bias voltage applied to the first pre-rod section 501A constant, both DC bias voltages are scanned simultaneously to search for, for example, a voltage at which the ion intensity becomes maximum. Specifically, when the DC bias voltage applied to the second pre-rod section 501B is VB2 and the DC bias voltage applied to the first pre-rod section 501A is VB1, the voltage value ratio VB2 / VB1 is fixed to a value determined by the following formula (8). VB2 / VB1={(L2 N1) / (L1 N2)} 2 …(8) Here, L2 and L1 are the lengths of the rod electrodes of the second and first pre-rod sections 501B and 501A, and N2 and N1 are the number of periods of the RF voltage in which ions reside in the second and first pre-rod sections 501B and 501A. In addition, it is sufficient that both the second and first pre-rod sections 501B and 501A satisfy the condition of the above formula (6). Note that the values ​​of n, m, and N (N1, N2) do not need to be the same in the second pre-rod section 501B and the first pre-rod section 501A.

[0053] The above formula (8) is obtained as follows. Let v2 and v1 be the speeds of the ions in the second and first pre-rod sections 501B and 501A, T be the time corresponding to one period of the RF voltage, e be the elementary charge, and m be the mass of the ion. L = (N T) v v = √(2 e VB / m) Therefore, VB2 / VB1=(v2 / v1) 2 ={(L2 / N2 T) / (L1 / N1 T)} 2 ={(L2 N1) / (L1 N2)} 2 It is.

[0054] For example, when L1=L2, N1=6, N2=3, m1=n1=m2=n2=1, VB2 / VB1=4. In this case, θx1=0.75π, θy1=0.25π, and θx2=θy2=0.5π. Therefore, in this case, the control unit 8 simultaneously scans the DC bias voltage VB2 applied to each rod electrode of the second pre-rod section 501B and the DC bias voltage VB1 applied to each rod electrode of the first pre-rod section 501A under the condition of VB2 / VB1=4, and searches for an optimal value of the voltage such that, for example, the ion intensity or the S / N ratio is the best or close to the best. In addition, since the optimal value of the DC bias voltage differs for each m / z, the control unit 8 can determine optimal values ​​for each of multiple m / z values, and during actual mass analysis, the DC bias voltage can be changed depending on the m / z of the ion to be analyzed.

[0055] In addition, in order to simplify the adjustment, the DC bias voltage is adjusted to correct the deviation from the condition that theoretically satisfies formula (6) so as to optimize the actual performance, but it is of course possible to perform a similar adjustment by adjusting the amplitude value of the RF voltage or the voltage value of the DC voltage. That is, by adjusting one or more of the RF voltage, DC voltage, and DC bias voltage applied to each rod electrode included in the pre-rod section 501, the deviation from the condition that satisfies formula (6) can be corrected so that the actual performance becomes the best (the best value under the condition that formula (2) is satisfied at that time).

[0056] [Use of injected lenses] As in the example shown in Fig. 2, when a DC voltage is applied to the pre-rod section 501 to convert the emittance of ions in the electric field, an injection lens capable of shaping the cross-sectional shape of the ion flow so as to match the shape of the emittance of ions at the inlet of the pre-rod section 501 can be provided at the inlet of the pre-rod section 501 in order to improve the efficiency of ion injection into the pre-rod section 501. Fig. 7 is a diagram showing an example of a configuration in which an injection lens 55 is provided and the emittance of ions at each section in that case. The injection lens 55 can be composed of, for example, a plurality of annular electrodes arranged along the ion optical axis C.

[0057] [Simulation and experiments to verify the effect] Next, a description will be given of simulations and experiments carried out to verify the effects of a mass spectrometer according to one aspect of the present invention.

[0058] FIG. 8 is a graph showing the results of a comparison of the ion transmission rate and peak shape between a mass spectrometer according to one embodiment of the present invention and a mass spectrometer using a conventional quadrupole mass filter, using a simulation. SIMION (registered trademark), an ion optical design software made by Scientific Instrument Services, Inc., USA, was used for the simulation. In the conventional device, no DC voltage is applied to the pre-rod section. On the other hand, in this device, the pre-rod section 501 has a two-stage configuration as shown in FIG. 4, an RF voltage of ±(0.8cosωt) is applied to the rod electrode of the second pre-rod section 501B, and an RF voltage of ±(0.95cosωt) and a DC voltage of ±0.7U are applied to the rod electrode of the first pre-rod section 501A.

[0059] As shown in FIG. 8(A), the ion transmission rate is clearly superior in this device. The reason for the improvement in ion transmission rate is presumed to be due to the appropriate conversion of emittance in the pre-rod section 501, as described above. As shown in FIG. 8(B), the peak shape is not as good as the ion transmission rate, but is superior in this device. The reason for the improvement in peak shape is presumed to be related to the finite length of the main rod section 500. In the conventional device, ions that would not be transmitted under the theoretical premise that the main rod section is infinite in length are transmitted because the length of the main rod section is finite, and the peak in the mass spectrum becomes broad. In contrast, in this device, the matching between the emittance of the pre-rod section 501 and the acceptance of the main rod section 500 is improved, and the performance as a mass filter is improved, and it is assumed that the phenomenon occurring in the conventional device is mitigated.

[0060] Figure 9 is a graph showing a comparison of the experimental results of analysis of reserpine using flow injection analysis for sample introduction with this device and a conventional device. The vertical axis of Figure 9 is the signal intensity ratio normalized with the maximum signal intensity of the conventional device set at 1, and the horizontal axis is time. As shown in Figure 9, the signal intensity of this device is clearly superior to that of the conventional device. This confirmed from the experimental results that the detection sensitivity is improved by improving the ion transmission rate.

[0061] Figure 10 is a graph showing a comparison of peak shapes when polyethylene glycol (PEG) was analyzed using the infusion analysis method for sample introduction with this device and a conventional device. The vertical axis of Figure 10 is the relative signal intensity normalized by the maximum signal intensity in each case. It was also confirmed from the experimental results that the peak shape was sharper with this device than with the conventional device.

[0062] It should be noted that the above-described embodiment and modified examples are merely examples of the present invention, and it is clear that any appropriate modifications, additions, and amendments made within the spirit of the present invention will also be encompassed within the scope of the claims of the present application.

[0063] For example, although the above-mentioned embodiment and modified examples are all triple quadrupole mass spectrometers using a quadrupole mass filter equipped with a pre-rod portion, it is clear that the present invention can also be applied to single-type quadrupole mass spectrometers and quadrupole-time-of-flight mass spectrometers. Furthermore, it is natural that components other than the quadrupole mass filter, such as the ion source, can be appropriately modified without being limited to those described above.

[0064] [Various aspects] It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0065] (Item 1) One aspect of the method for driving a quadrupole mass filter according to the present invention is a method for operating a quadrupole mass filter comprising a main rod section including four rod electrodes arranged to surround a central axis, and a first pre-rod section including four rod electrodes arranged at a position upstream of the main rod section in the extension direction of the central axis, the method comprising: a voltage calculation step of determining DC voltage Up and RF voltage amplitude Vp (where the relationship between Up, Vp, a, and q is defined by the above formulas (3) and (4)) such that, when a direction connecting the centers of a pair of rod electrodes facing each other across the central axis in a plane perpendicular to the central axis is defined as the X-axis direction and a direction connecting the centers of another pair of rod electrodes is defined as the Y-axis direction, and β values ​​(0<β<1) related to the secular oscillation of ions in each of the X and Y directions are defined as βx and βy, respectively, the a-values ​​and q-values ​​which are parameters of the Mathieu equation expressing ion motion and have the relationship between βx, βy, and the above formulas (1) and (2), a≠0, (π-βx·π)N={(1 / 2)+m}π, and βy·π·N={(1 / 2)+n}π, (where m, n, and N are natural numbers); a voltage application step of applying, during analysis, a voltage obtained by superimposing a DC voltage corresponding to the m / z of a target ion and an RF voltage corresponding to the m / z to each rod electrode of the main rod section, and applying, to each rod electrode of the first pre-rod section, a voltage obtained by superimposing an RF voltage ±Vp cosωt having the same frequency and amplitude as the RF voltage applied to the main rod section and a DC voltage ±Up having a different voltage value from the DC voltage applied to the main rod section; has.

[0066] (Item 9) One aspect of the quadrupole mass spectrometer according to the present invention is a quadrupole mass filter including a main rod section including four rod electrodes arranged to surround a central axis, and a first pre-rod section including four rod electrodes arranged to surround the central axis at a position upstream of the main rod section along the front central axis in the ion flow; a main voltage application unit that applies a voltage obtained by superposing a DC voltage corresponding to the m / z of an ion and an RF voltage corresponding to the m / z to each rod electrode of the main rod unit in order to form a quadrupole electric field in the main rod unit; an auxiliary voltage application unit that applies a voltage obtained by superimposing an RF voltage ±Vp·cosωt having the same frequency as the RF voltage and a DC voltage ±Up having a voltage value different from the DC voltage applied to the main rod unit to each rod electrode of the first pre-rod unit in order to form a quadrupole electric field in the first pre-rod unit; a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: when a direction connecting the centers of a pair of rod electrodes opposing each other across the central axis in a plane perpendicular to the central axis is defined as an X-axis direction, and a direction connecting the centers of another pair of rod electrodes is defined as a Y-axis direction, and β values ​​(0<β<1) related to the secular oscillation of ions in each of the X and Y directions are defined as βx and βy, the parameters of the Mathieu equation expressing the motion of ions are related to Up and Vp by the above formulas (3) and (4), and βx and βy are related to the above formulas (1) and (2), the values ​​of a and q are a ≠ 0, and (π-βx π)N={(1 / 2)+m}π and βy π π N={(1 / 2)+n}π, (where m, n, and N are natural numbers).

[0067] In the method for driving a quadrupole mass filter described in paragraph 1 and the quadrupole mass spectrometer described in paragraph 9, when ions pass through the pre-rod section, the cross-sectional shape of the emittance of the ions is appropriately converted in both the X-axis direction and the Y-axis direction by the action of the electric field formed in the pre-rod section, and the ions are delivered to the main rod section in a state of being concentrated in the center of the phase space. Therefore, the loss of ions when the ions that have passed through the pre-rod section enter the main rod section is reduced more than before, and the overall ion transmission efficiency in the quadrupole mass filter can be improved. Therefore, according to the method for driving a quadrupole mass filter described in paragraph 1 and the quadrupole mass spectrometer described in paragraph 9, the amount of ions sent to a device downstream of the quadrupole mass filter, such as an ion detector or a collision cell, can be increased, and analytical sensitivity can be improved.

[0068] (Item 2, Item 10) In the method for driving a quadrupole mass filter according to item 1 and the quadrupole mass spectrometer according to item 9, N may be in the range of 3 or more and 20 or less.

[0069] (Item 3, Item 11) In the method for driving a quadrupole mass filter according to item 2 and the quadrupole mass spectrometer according to item 10, N may be in the range of 4 or more and 10 or less.

[0070] (Item 4, Item 12) In the method for driving a quadrupole mass filter according to item 3 and the quadrupole mass spectrometer according to item 11, N may be 6.

[0071] N is the time that ions are present in the pre-rod portion expressed by the number of periods of the RF voltage, and theoretically there is no restriction on its value. However, if N is too small, it is difficult to convert the emittance sufficiently to concentrate the emittance of the ions in the center, and conversely, if N is too large, it is difficult to sufficiently control the behavior of the ions with respect to the variation in the angle at which the ions are incident on the pre-rod portion. Therefore, there is a practical restriction on the range of values ​​that N can take, and N should be in the range of 3 to 20, more preferably in the range of 4 to 10, and most preferably 6.

[0072] (Item 5, Item 13) In the method for driving a quadrupole mass filter according to item 1 and the quadrupole mass spectrometer according to item 9, n and m may each be 1 or 2.

[0073] (Item 6, Item 14) In the method for driving a quadrupole mass filter according to Item 5 and the quadrupole mass spectrometer according to Item 13, n and m may be the same.

[0074] That is, the combination of n and m is either n=m=1, n=1 and m=2, n=2 and m=1, or n=m=2. In theory, there are no restrictions on the values ​​of n and m, but in practice, it is better for n and m to have small values, and if possible, it is better for them to have the same values.

[0075] (Items 7 and 15) In the method of driving the quadrupole mass filter described in item 1 and the quadrupole mass spectrometer described in item 9, βx and βy may satisfy the relationship βx+βy=1.

[0076] (Item 8) In the method of driving a quadrupole mass filter described in Item 7, in the voltage setting step, Up and Vp can be determined so that the a and q values ​​substantially satisfy βx=3 / 4 and βy=1 / 4.

[0077] (Item 16) Similarly, the quadrupole mass spectrometer described in Item 15 may be configured such that the voltage in the auxiliary voltage application unit is set so that the a and q values ​​substantially satisfy βx=3 / 4 and βy=1 / 4.

[0078] According to the method of driving a quadrupole mass filter described in items 7 and 8, and the quadrupole mass spectrometer described in items 15 and 16, it is possible to greatly improve ion transmission efficiency and sufficiently increase detection sensitivity compared to conventional devices.

[0079] (Item 17) In the quadrupole mass spectrometer according to item 9, The quadrupole mass filter has a second pre-rod section including four rod electrodes in a stage preceding the first pre-rod section, The auxiliary voltage application section may apply an RF voltage having the same frequency as the RF voltage, without superimposing a DC voltage for forming a quadrupole electric field, to each rod electrode of the second pre-rod section.

[0080] (Item 18) In the quadrupole mass spectrometer described in Item 17, the RF voltage applied to each rod electrode of the second pre-rod section can be set to a q value that satisfies βx=1 / 2, βy=1 / 2 (wherein r0 included in the equation defining this q value is the distance from the central axis to each rod electrode of the second pre-rod section).

[0081] According to the quadrupole mass spectrometer described in items 17 and 18, ions can be efficiently sent to the main rod section while maintaining the incidence efficiency of ions sent from the previous stage into the pre-rod section at the same level as in conventional devices, so that the ion transmission efficiency can be further improved.

[0082] (Item 19) In the quadrupole mass spectrometer described in Item 17, the auxiliary voltage application section can further apply DC bias voltages of different voltage values ​​to the first pre-rod section and the second pre-rod section.

[0083] (Item 20) In the quadrupole mass spectrometer described in Item 19, the relationship between the DC bias voltage VB1 applied to each rod electrode of the first pre-rod section and the DC bias voltage VB2 applied to each rod electrode of the second pre-rod section is expressed as follows: VB2 / VB1={(L2×N1) / (L1×N2)} where L1 is the length of the rod electrode of the first pre-rod section, L2 is the length of the rod electrode of the second pre-rod section, N1 is the number of periods of the RF voltage corresponding to the time for which ions pass through the first pre-rod section, and N2 is the number of periods of the RF voltage corresponding to the time for which ions pass through the second pre-rod section. 2 The value may be set to

[0084] (Item 21) In the quadrupole mass spectrometer described in Item 20, the relationship between the DC bias voltages VB1 and VB2 is VB2 / VB1={(L2×N1) / (L1×N2)} 2 The power supply voltage VB1 may be fixed at VB2, and the DC bias voltages VB2 and VB1 may be changed to optimize the parameters.

[0085] According to the quadrupole mass spectrometer described in items 19 to 21, the optimization adjustment can be simplified and the time required for the optimization adjustment can be shortened compared to the case where the optimization adjustment of parameters is performed individually in the multiple stages of pre-rod parts.

[0086] (Item 22) The quadrupole mass spectrometer described in Item 9 may further include an ion injection lens in front of the pre-rod portion that is disposed at the frontmost position in the quadrupole mass filter, for narrowing the spread of ions around the central axis.

[0087] According to the quadrupole mass spectrometer described in item 22, the efficiency of ions being incident on the pre-rod portion can be improved, and the ion transmission efficiency can be further increased.

[0088] (Item 23) The quadrupole mass spectrometer described in Item 9 may further include a control unit that adjusts at least one of the RF voltage or DC voltage for forming a quadrupole electric field, or the DC bias voltage, which is applied from the voltage application unit to each rod electrode of the pre-rod unit, to near a set value based on an ion intensity signal obtained by the detector.

[0089] According to the quadrupole mass spectrometer described in paragraph 23, even if there is variation in the length of the rod electrodes or a change in the state of the device after the parameters such as the voltage value are determined, the parameters can be appropriately adjusted to approach an ideal state, and the detection sensitivity can be reliably improved.

[0090] Furthermore, one aspect of a method for adjusting a quadrupole mass spectrometer related to the present invention is a method for adjusting a quadrupole mass spectrometer including a quadrupole mass filter composed of a main rod section including four rod electrodes arranged to surround a central axis and a first pre-rod section including four rod electrodes arranged in front of the main rod section along the central axis, and a voltage application section that applies voltages to each rod electrode of the main rod section and each rod electrode of the pre-rod section, At least one of the RF voltage, DC voltage, or DC bias voltage for forming a quadrupole electric field applied from the voltage application unit to each rod electrode of the pre-rod unit is adjusted based on the ion detection results, within a range in which the a and q values, which are parameters of the Mathieu equation representing the motion of ions, satisfy the conditions of the stable region of the Mathieu diagram and a≠0.

[0091] This method of adjusting a quadrupole mass spectrometer reduces the loss of ions when they pass through the pre-rod section and enter the main rod section, and improves the overall ion transmission efficiency in the quadrupole mass filter, thereby increasing the amount of ions sent to devices downstream of the quadrupole mass filter, such as an ion detector or a collision cell, and improving analytical sensitivity.

[0092] In addition, in the above-mentioned method for adjusting a quadrupole mass spectrometer, the RF voltage and DC voltage for forming a quadrupole electric field among the voltages applied to each rod electrode of the pre-rod section are design values, and the DC bias voltage can be adjusted based on the detection result of ions under the design values.

[0093] Furthermore, in the above-mentioned method for adjusting a quadrupole mass spectrometer, the DC voltage value Up and the amplitude value Vp of the RF voltage applied to each rod electrode of the pre-rod section can be determined so as to substantially satisfy the following conditions: when the direction connecting the centers of a pair of rod electrodes opposing each other across the central axis in a plane perpendicular to the central axis is the X-axis direction, and the direction connecting the centers of the other pair of rod electrodes is the Y-axis direction, and β values ​​(0<β<1) related to the secular oscillation of ions in each of the X and Y directions are βx and βy, the parameters of the Mathieu equation expressing the motion of ions have the relationships with Up and Vp as shown in the above formulas (3) and (4), and βx and βy have the relationships with the above formulas (1) and (2), respectively, a and q are (π-βx·π)N={(1 / 2)+m}π, and βy·π·N={(1 / 2)+n}π, (where m, n, and N are natural numbers).

[0094] According to these methods for adjusting a quadrupole mass spectrometer, even if there is variation in the length of the rod electrodes or a change in the state of the device, the parameters can be appropriately adjusted to a state close to that assumed at the time of design, thereby reliably increasing the detection sensitivity. [Explanation of symbols]

[0095] 1. Vacuum chamber 2...First intermediate vacuum chamber 20…Ion Guide 21...Skimmer 3...Second intermediate vacuum chamber 30…Ion Guide 4…Third intermediate vacuum chamber 40…Ion Guide 5…Analysis room 50…Pre-quadrupole mass filter 500…Main rod section 5001, 5002, 5003, 5004...Rod electrodes 501…Pre-rod section 5011, 5012, 5013, 5014...Pre-rod electrode 502…Post rod section 51…Collision cell 52…Ion Guide 53...Post-quadrupole mass filter 530…Main rod section 531…Pre-rod section 54…Ion detector 6…Ionization section 60…Ionization chamber 61…ESI probe 62...Desolvation tube 7...Power supply section 8...Control section

Claims

1. 1. A method for operating a quadrupole mass filter comprising: a main rod section including four rod electrodes arranged to surround a central axis; and a first pre-rod section including four rod electrodes arranged upstream of an ion flow in an extension direction of the central axis relative to the main rod section, the method comprising: a voltage calculation step of determining a DC voltage Up and an amplitude Vp of an RF voltage (wherein the relationship between Up, Vp, a, and q is defined by the following formulas (3) and (4)) such that, when a direction connecting the centers of a pair of rod electrodes facing each other across the central axis in a plane perpendicular to the central axis is defined as the X-axis direction, and a direction connecting the centers of another pair of rod electrodes is defined as the Y-axis direction, and β values ​​(0<β<1) related to the secular oscillation of ions in each of the X and Y directions are defined as βx and βy, respectively, the a and q values ​​being parameters of the Mathieu equation that expresses the motion of ions and having the relationship between βx and βy and the following formulas (1) and (2), a≠0, and (π-βx.π)N={(1 / 2)+m}π, and βy.π.N={(1 / 2)+n}π, (wherein m, n, and N are natural numbers); a voltage application step of applying, to each rod electrode of the main rod section during analysis, a voltage obtained by superimposing a DC voltage corresponding to the m / z of the target ion and an RF voltage corresponding to the m / z, and applying, to each rod electrode of the first pre-rod section, a voltage obtained by superimposing an RF voltage ±Vp·cosωt having the same frequency and amplitude as the RF voltage applied to the main rod section and a DC voltage ±Up having a different voltage value from the DC voltage applied to the main rod section; A method for driving a quadrupole mass filter having the above structure. [0010] [0025] [0030] [0045] where e is the charge of the ion, m is the mass of the ion, and r 0 is the distance from the central axis to each rod electrode of the first pre-rod section, and ω is the angular frequency of the RF voltage.

2. 2. The method of driving a quadrupole mass filter according to claim 1, wherein N is in the range of 3 or more and 20 or less.

3. 3. The method of driving a quadrupole mass filter according to claim 2, wherein N is in the range of 4 or more and 10 or less.

4. 4. The method of driving a quadrupole mass filter according to claim 3, wherein N is 6.

5. 2. The method of driving a quadrupole mass filter according to claim 1, wherein n and m are each 1 or 2.

6. 6. The method of driving a quadrupole mass filter according to claim 5, wherein n and m are the same.

7. 2. The method of driving a quadrupole mass filter according to claim 1, wherein βx and βy satisfy a relationship of βx+βy=1.

8. 8. The method of driving a quadrupole mass filter according to claim 7, wherein in said voltage setting step, Up and Vp are determined so as to obtain a and q values ​​that substantially satisfy βx = 3 / 4 and βy = 1 / 4.

9. a quadrupole mass filter including a main rod section including four rod electrodes arranged to surround a central axis, and a first pre-rod section including four rod electrodes arranged to surround the central axis at a position upstream of the main rod section along the central axis in the ion flow; a main voltage application unit that applies a voltage obtained by superposing a DC voltage corresponding to the m / z of an ion and an RF voltage corresponding to the m / z to each rod electrode of the main rod unit in order to form a quadrupole electric field in the main rod unit; an auxiliary voltage application unit that applies a voltage obtained by superimposing an RF voltage ±Vp·cosωt having the same frequency as the RF voltage and a DC voltage ±Up having a voltage value different from the DC voltage applied to the main rod unit to each rod electrode of the first pre-rod unit in order to form a quadrupole electric field in the first pre-rod unit; a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: a DC voltage value Up and an amplitude value Vp of an RF voltage applied to the auxiliary voltage application unit are determined so as to substantially satisfy the following conditions: [0010] [0025] [0030] [0045] where e is the charge of the ion, m is the mass of the ion, and r 0 is the distance from the central axis to each rod electrode of the first pre-rod section, and ω is the angular frequency of the RF voltage.

10. The quadrupole mass spectrometer according to claim 9 , wherein N is in the range of 3 to 20.

11. The quadrupole mass spectrometer according to claim 10 , wherein N is in the range of 4 to 10.

12. 12. The quadrupole mass spectrometer of claim 11, wherein N is 6.

13. 10. The quadrupole mass spectrometer according to claim 9, wherein n and m are each 1 or 2.

14. 14. The quadrupole mass spectrometer of claim 13, wherein n and m are the same.

15. 10. The quadrupole mass spectrometer according to claim 9, wherein βx and βy satisfy a relationship of βx+βy=1.

16. 16. The quadrupole mass spectrometer according to claim 15, wherein the voltage in the auxiliary voltage application unit is set so that the a and q values ​​substantially satisfy βx = 3 / 4 and βy = 1 / 4.

17. the quadrupole mass filter has a second pre-rod section including four rod electrodes in a stage preceding the first pre-rod section, The quadrupole mass spectrometer according to claim 9, wherein the auxiliary voltage application unit applies an RF voltage having the same frequency as the RF voltage and not superimposed with a DC voltage for forming a quadrupole electric field, to each rod electrode of the second pre-rod unit.

18. The RF voltage applied to each rod electrode of the second pre-rod section is a q value that satisfies βx=1 / 2 and βy=1 / 2 (where r 0 The quadrupole mass spectrometer according to claim 17, wherein the distance is set so that the distance from the central axis to each rod electrode of the second pre-rod section.

19. 18. The quadrupole mass spectrometer according to claim 17, wherein the auxiliary voltage application section further applies DC bias voltages having different voltage values ​​to the first pre-rod section and the second pre-rod section.

20. The relationship between the DC bias voltage VB1 applied to each rod electrode of the first pre-rod section and the DC bias voltage VB2 applied to each rod electrode of the second pre-rod section is expressed as follows, where L1 is the length of the rod electrode of the first pre-rod section, L2 is the length of the rod electrode of the second pre-rod section, N1 is the number of periods of the RF voltage corresponding to the time for which ions pass through the first pre-rod section, and N2 is the number of periods of the RF voltage corresponding to the time for which ions pass through the second pre-rod section: VB2 / VB1={(L2×N1) / (L1×N2)} 2 20. The quadrupole mass spectrometer of claim 19, wherein the quadrupole mass spectrometer is set to

21. The relationship between the DC bias voltages VB1 and VB2 is VB2 / VB1={(L2×N1) / (L1×N2)} 2 21. The quadrupole mass spectrometer according to claim 20, further comprising a parameter adjustment section that optimizes and adjusts the parameters by varying the DC bias voltages VB1 and VB2 while keeping the DC bias voltages VB1 and VB2 fixed.

22. 10. The quadrupole mass spectrometer according to claim 9, further comprising an ion injection lens for narrowing the spread of ions around a central axis, in front of a pre-rod portion disposed at the frontmost position in the quadrupole mass filter.

23. The quadrupole mass spectrometer according to claim 9, further comprising a control unit that adjusts at least one of the RF voltage, DC voltage, or DC bias voltage for forming a quadrupole electric field, which is applied from the voltage application unit to each rod electrode of the pre-rod unit, to a value close to a set value based on an ion intensity signal obtained by the detector.

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