Control Method of Mass Analyzer, Mass Analysis System, and Voltage Control Device

Abstract

For high-efficiency quality analysis, it is characterized by having a quality analysis device, the quality analysis device including: an ion source, an ion guide, a quadrupole mass filter, and a detector disposed at the subsequent stage of the quadrupole mass filter, and including a DC power supply and an RF power supply, as well as a voltage control device for controlling the DC voltage, i.e., the acceleration voltage, by controlling the power supply, a voltage control unit. In a coordinate system where one coordinate axis represents the mass-to-charge ratio of ions passing through the ion guide and the other coordinate axis represents the acceleration voltage applied to the ion guide unit, within a control region (RA) surrounded by a line (L11) at the lower limit value of the stable region where ions stably pass through the ion guide, a line (L12) of the ion mobility of the ions, an upper side (L13) which is the upper limit value of the acceleration voltage, and a lower side (L14) where the acceleration voltage is zero, the acceleration voltage is controlled according to a control line (L21) such that the larger the mass-to-charge ratio of the measured ions, the larger the acceleration voltage.

Description

Technical Field

[0001] The present invention relates to techniques for a control method of a mass analyzer, a mass analysis system, and a voltage control device. Background Art

[0002] Generally, an ion source under atmospheric pressure is used to generate ions in a mass analyzer, and a quadrupole mass filter or the like under vacuum is used to separate the generated ions according to the mass-to-charge ratio (m / z). An ion guide or the like of a plasma optical system is used to converge the ions generated under atmospheric pressure and efficiently introduce them into the quadrupole mass filter under vacuum. In particular, in a mass analyzer that uses a quadrupole mass filter for mass separation of ions, a multipole ion guide is widely used. The multipole ion guide has a high effect of converging ions and can share a high-frequency voltage with the quadrupole mass filter, so it is inexpensive.

[0003] Patent Document 1 discloses a method of accelerating ions by forming an electric field on the central axis of a multipole ion guide. In Patent Document 1, it is disclosed that the time required for ions to pass through the ion guide is shortened by accelerating the ions with an axial electric field.

[0004] Prior Art Documents

[0005] Patent Documents

[0006] Patent Document 1: Specification of U.S. Patent No. 5,847,386 Summary of the Invention

[0007] Problems to be Solved by the Invention

[0008] In a multipole ion guide, the m / z range of ions that can stably pass through depends on the applied high-frequency voltage. When sharing the high-frequency voltage with a quadrupole mass filter, it is set so that the sample ions measured by the mass analyzer can pass through the ion guide efficiently. Ions with an m / z larger than that of the sample ions measured by the mass analyzer cannot stably pass through the ion guide and are excluded from the inside of the ion guide. Therefore, when switching the m / z of the sample ions measured by the mass analyzer, no ions can be observed during the time when the sample ions generated by the ion source pass through the ion guide and reach the quadrupole mass filter, and there is a problem of reduced sensitivity.

[0009] In the method disclosed in Patent Document 1, ions are accelerated by an axial electric field to shorten the time required for the ions to pass through the ion guide. By doing so, it is possible to suppress a decrease in sensitivity when switching the m / z of the sample ions measured by the mass analyzer. However, in the structure in which an electrode is inserted between the ion guide rod electrodes of the ion guide, there is a problem that when the electrode inserted between the ion guide rod electrodes of the ion guide is contaminated, the sensitivity is greatly reduced due to charging. On the other hand, in the structure in which the ion guide rod electrodes of the ion guide are tilted and the structure using tapered rod electrodes, the voltage applied to form the axial electric field applies a quadrupole static voltage in the radial direction of the ion guide. Therefore, there is a problem that the range of m / z that can stably pass through the ion guide is limited.

[0010] The present invention has been made in view of such a background, and an object of the present invention is to perform mass analysis with high efficiency.

[0011] Technical means for solving the problem

[0012] In order to solve the above problems, the present invention is characterized in that it includes a mass analyzer, a power supply, and a voltage control unit. The mass analyzer includes: an ion source that generates ions; an ion guide disposed at a subsequent stage of the ion source that converges the ions; a mass filter disposed at a subsequent stage of the ion guide that separates the ions converged by the ion guide according to the mass-to-charge ratio; and a detector disposed at a subsequent stage of the mass filter that detects the ions separated by the mass filter. The power supply applies at least an alternating voltage biased by a direct current voltage to the ion guide. The voltage control unit controls the direct current voltage, that is, the acceleration voltage, by controlling the power supply. The voltage control unit, in a coordinate system where one coordinate axis represents the mass-to-charge of the ions passing through the ion guide and the other coordinate axis represents the acceleration voltage applied to the ion guide, controls the acceleration voltage in a control region surrounded by the lower limit value of the stable region where the ions stably pass through the ion guide, the ion mobility of the ions, the upper limit value of the acceleration voltage, and the value where the acceleration voltage is zero, such that the larger the mass-to-charge ratio of the measured ions, the larger the acceleration voltage.

[0013] Other solutions will be appropriately described in the embodiments.

[0014] Advantages of the invention

[0015] According to the present invention, high-efficiency mass analysis can be performed. Description of the drawings

[0016] Figure 1 It is a structural diagram of the mass analysis system of the first embodiment.

[0017] Figure 2A It is a diagram (one of them) showing the structure of a quadrupole mass filter.

[0018] Figure 2B It is a diagram (the second one) showing the structure of a quadrupole mass filter.

[0019] Figure 3 It is a diagram showing the stable region in a quadrupole mass filter.

[0020] Figure 4A It is a diagram (one of them) showing the structure of the ion guide in this embodiment.

[0021] Figure 4B It is a diagram (the second one) showing the structure of the ion guide in this embodiment.

[0022] Figure 4C It is a diagram (the third one) showing the structure of the ion guide in this embodiment.

[0023] Figure 4D It is a diagram (the fourth one) showing the structure of the ion guide in this embodiment.

[0024] Figure 5 It is a graph showing the relationship between the distance in the ion guide and the voltage on the central axis obtained by simulation.

[0025] Figure 6 It is a graph showing the relationship between the ion passing time through the ion guide and the amount of ions obtained by simulation.

[0026] Figure 7 It is a diagram with the horizontal axis set as the q value and the vertical axis set as the a value for the stable region in the ion guide.

[0027] Figure 8 It is a schematic diagram showing the amount of ion signal when switching m / z from m1 to m2.

[0028] Figure 9 It is a diagram showing the control method of the mass analysis system of the first embodiment.

[0029] Figure 10 It is a diagram showing the control method of the mass analysis system of the second embodiment.

[0030] Figure 11 It is a structural diagram of the mass analysis system of the third embodiment.

[0031] Figure 12 It is a diagram showing the control method of the mass analysis system of the third embodiment.

[0032] Figure 13It is a flowchart showing the process of the control method of the quality analysis system according to the third embodiment.

[0033] Figure 14A It is a graph showing the time variation of the acceleration voltage.

[0034] Figure 14B It is a graph showing the time variation of the m / z of the ions measured by the quality analysis system.

[0035] Figure 15 It is a functional block diagram showing the structure of the voltage control device of this embodiment. Detailed Embodiment

[0036] Next, the embodiments for implementing the present invention (referred to as "embodiments") will be described in detail with appropriate reference to the accompanying drawings.

[0037] [First Embodiment]

[0038] <Mass Spectrometer 100>

[0039] Figure 1 It is a structural diagram of the mass analysis system 1 according to the first embodiment.

[0040] The mass analysis system 1 includes a mass spectrometer 100, a voltage control device 200, DC power supplies 301 and 303, and an RF power supply 302.

[0041] In the mass spectrometer 100, the ions generated by the ion source 151 are introduced into the first differential pumping section 101 through the orifice 121. The ion source 151 is an ion source that operates at atmospheric pressure or in a low vacuum, such as an electrospray ion source, an atmospheric pressure chemical ionization source, an atmospheric pressure photoionization source, or an atmospheric pressure matrix-assisted laser desorption ionization source.

[0042] For the first differential pumping section 101, it is evacuated by the pump 111 to maintain a vacuum degree of 10 Pa to 500 Pa. The ions that have passed through the first differential pumping section 101 are introduced into the second differential pumping section 102 through the orifice 122. For the second differential pumping section 102, it is evacuated by the pump 112 to maintain a vacuum degree of 0.1 Pa to 10 Pa. An ion guide 130 for converging ions is provided in the second differential pumping section 102.

[0043] In the second differential exhaust section 102, since droplets and inclusions in the atmosphere flow in from the ion source 151 under atmospheric pressure, it is more prone to contamination than the analysis section 103 with a high degree of vacuum. When the electrodes of the ion guide 130 are contaminated, charging occurs and the sensitivity of the mass spectrometry device 100 decreases. Therefore, the ion guide 130 is structured to be less affected by contamination than the ion optical system provided in the analysis section 103. The ions converged by the ion guide 130 are introduced into the analysis section 103 provided with the quadrupole mass filter 140 through the fine hole 123. In the quadrupole mass filter 140, the ions are separated according to the mass-to-charge ratio. For the analysis section 103, it is evacuated by the pump 113 and maintained at a pressure of 1E-3 Pa or less. The ions that have passed through the quadrupole mass filter 140 are detected by the detector 152. As the detector 152, an electron multiplier or a detector of a type combining a scintillator and a photomultiplier is generally used.

[0044] The voltage control device 200, DC power supplies 301, 303, RF power supply 302, and dielectric 153 will be described later.

[0045] <Quadrupole Mass Filter 140>

[0046] Figure 2A and Figure 2B is a diagram showing the structure of the quadrupole mass filter 140.

[0047] As Figure 2A and Figure 2B shown, the quadrupole mass filter 140 is composed of four quadrupole electrodes 141 (141a to 141d). For the quadrupole electrodes 141, a high-frequency voltage (hereinafter referred to as RF voltage) and a static voltage (hereinafter referred to as DC voltage) are applied in such a way that the adjacent quadrupole electrodes 141 are out of phase and the opposing quadrupole electrodes 141 are in phase. Here, the RF voltage is an alternating voltage generated by the RF power supply 302 controlled by the voltage control device 200. That is, out-of-phase RF voltages are applied between a pair of quadrupole electrodes 141a, 141c and a pair of quadrupole electrodes 141b, 141d.

[0048] In addition, the DC voltage is a voltage generated by the DC power supply 301 controlled by the voltage control device 200. Here, when the DC voltage applied to the quadrupole electrodes 141a, 141c is VDC1, the DC voltage applied to the quadrupole electrodes 141b, 141d is -VDC1. The applied RF voltage and DC voltage are appropriately referred to as the quadrupole RF voltage and the quadrupole DC voltage, respectively. The typical voltage amplitude of the quadrupole RF voltage is several hundred V to several kV, and the frequency is on the order of 500 kHz to 2 MHz. The voltage value of the quadrupole DC voltage is on the order of several tens of V to several hundred V.

[0049] The operation of the quadrupole mass filter 140 will be described. The m / z range of ions that can perform stable orbital motion within the quadrupole mass filter 140 depends on the amplitude of the quadrupole RF voltage and the value of the quadrupole DC voltage. Only ions present within Figure 3 the stable regions R1 to R3 shown can pass through the quadrupole mass filter 140. Here, the stable region R1 is the region within the line R1a, the stable region R2 is the region within the line R2a, and the stable region R3 is the region within the line R3a. The stable regions R1 to R3 are different for each ion's m / z and are arranged in the order Figure 3 shown from ions with a smaller m / z to those with a larger m / z. That is, the stable region R1 is the stable region for ions with a certain m / z. Similarly, the stable region R2 is the stable region for ions with an m / z different from that of the ions in the stable region R1, and the stable region R3 is the stable region for ions with an m / z different from that of the ions in the stable regions R1 and R2.

[0050] If the quadrupole RF voltage and the quadrupole DC voltage are set near the vertices of the stable regions R1 to R3 for a certain m / z, only ions with that m / z can pass through. Additionally, if the relationship between the quadrupole RF voltage and the quadrupole DC voltage is maintained in such a way that Figure 3 as shown by the scan line L1 in

[0051] <Ion guide 130>

[0052] Figures 4A - 4D This is a diagram showing the structure of the ion guide 130 in the present embodiment.

[0053] As Figures 4A - 4D shown, the ion guide 130 is composed of four ion guide rod electrodes 131 (131a to 131d). As Figures 4A - 4D shown, a specific pair of opposing ion guide rod electrodes 131 (ion guide rod electrodes 131a and 131c) among the ion guide rod electrodes 131 use electrodes having a shape obtained by obliquely cutting a part of a cylinder with respect to the bottom surface from the cylinder. Then, the ion guide rod electrodes 131a and 131c are arranged as Figure 4B shown with their cut surfaces facing the direction of the central axis AC of the ion guide 130. Additionally, the other pair (ion guide rod electrodes 131b and 131d) has a cylindrical shape.

[0054] In Figure 4B is shown a cross-sectional view of the ion guide 130 in the axial direction, and in Figure 4CFIG. shows a radial cross-sectional view as seen from the entrance of the ion guide 130 ( Figure 4B cross-sectional view taken along line A-A), and in Figure 4D FIG. shows a radial cross-sectional view as seen from the exit of the ion guide 130 ( Figure 4B cross-sectional view taken along line B-B).

[0055] As Figure 4C shown, on the radial cross-section at the entrance of the ion guide 130, the distance Da is longer than the distance Db. Here, the distance Da is the distance between the central axis AC of the ion guide 130 (refer to Figure 4B ) and the lower end of the ion guide rod electrode 131a (or the upper end of the ion guide rod electrode 131c). Additionally, the distance Db is the distance between the central axis AC of the ion guide 130 (refer to Figure 4B ) and the inner end of the ion guide rod electrode 131b (or the inner end of the ion guide rod electrode 131d). The closer to the exit of the ion guide 130 from the entrance of the ion guide 130, the smaller the difference between the distance Da and the distance Db. Then, as Figure 4D shown, at the exit of the ion guide 130, the distance Da is equal to the distance Db.

[0056] For the opposing specified ion guide rod electrodes 131a and 131c, an RF voltage of the same phase is applied using the RF power supply 302. Additionally, for the other opposing ion guide rod electrodes 131b and 131d, an RF voltage of a phase opposite to that of the ion guide rod electrodes 131a and 131c is applied using the RF power supply 302. The phase of the applied RF voltage is adjusted by controlling the RF power supply 302 with the power supply control device 200. Additionally, the amplitude of the RF voltage applied to the ion guide 130 is 10 V to 5000 V, and the frequency is on the order of 500 kHz to 2 MHz. The amplitude of the RF voltage applied to the ion guide 130 and the amplitude of the RF voltage applied to the quadrupole mass filter 140 are different due to the presence of the dielectric 153.

[0057] As described above, the RF voltage is supplied from the RF power supply 302 controlled by the voltage control device 200 to the quadrupole electrodes 141 of the quadrupole mass filter 140 (refer to Figure 2A and Figure 2B ). Then, from the quadrupole electrodes 141, it is supplied to the ion guide rod electrodes 131 of the ion guide 130 through a dielectric 153 such as a capacitor. With such a structure, compared to a structure where the RF voltage is supplied individually to the ion guide 130 and the quadrupole mass filter 140, the number of power supplies can be reduced, and the mass analysis system 1 can be made less expensive.

[0058] The ratio α of the amplitude V of the RF voltage applied to the ion guide 130 to the amplitude V of the RF voltage applied to the quadrupole mass filter 140 is given by the following formula (1-1) or formula (1-2). 0 Here, C

[0059] [Mathematical formula 1]

[0060]

[0061]

[0062] is the electrostatic capacitance of the dielectric 153, C 1 is the electrostatic capacitance of the ion guide rod electrode 131, R is the resistance between the ion guide rod electrode 131 and the DC power supply 303, and ω is the frequency of the RF power supply. 2 Here, a DC voltage is also applied to the ion guide rod electrode 131 in addition to the RF voltage. As

[0063] shown, a DC voltage is supplied from the DC power supply 303 controlled by the voltage control device 200 to the ion guide rod electrode 131. The ion guide 130 and the quadrupole mass filter 140 are separated by the dielectric 153, so separate DC voltages can be applied. That is, the DC voltage applied to the quadrupole mass filter 140 from the DC power supply 301 is not affected by the dielectric 153 and does not affect the ion guide 130. Then, the RF voltage applied to the ion guide rod electrode 131 is biased by the DC voltage applied by the DC voltage 303. Figure 4D

[0064] In addition, when the DC voltage applied to a pair of ion guide rod electrodes 131a and 131c is +VDC, a DC voltage of -VDC is applied to the DC voltage applied to a pair of ion guide rod electrodes 131b and 131d. The difference between the DC voltage applied to a pair of ion guide rod electrodes 131a and 131c and the DC voltage applied to a pair of ion guide rod electrodes 131b and 131d is called the acceleration voltage, and the average is called the bias voltage. When the DC voltage applied by the DC power supply 303 is VDC, the acceleration voltage is 2VDC. Hereafter, it is assumed that the RF voltages applied to the ion guide rod electrode 131 and the quadrupole electrode 141 are biased by DC voltages.

[0065] As described above, at the vicinity of the outlet of the ion guide 130, the distances Da and Db are equal. An axial electric field is not formed at the place where the distances Da and Db are equal. Here, the axial electric field is the electric field generated on the central axis AC due to the acceleration voltage applied to the ion guide rod electrode 131.

[0066] That is, as Figure 4B ​As shown, in the range of about 0.5 cm to 5 cm starting from near the outlet of the ion guide 130, a cooling section 401 is provided where the distance Da and the distance Db are equal and no axial electric field is formed. In the cooling section 401, in addition to not forming an axial electric field, since each ion guide rod electrode 131 is at an equal distance from the central axis AC, the RF voltage on the central axis AC is also zero. Therefore, the spatial distribution and kinetic energy distribution of ions can be converged with good efficiency.

[0067] Figures 4A - 4D The ion guide 130 shown has a small number of components, and the ion guide rod electrode 131 has a simple shape such as a cylinder or a part of a cut cylinder, so it is easy to process and can be manufactured inexpensively. In addition, as described above, when the electrode surface of the ion guide 130 is contaminated by droplets and inclusions, the sensitivity of the mass analyzer 100 decreases due to charging caused by the contamination. However, Figures 4A - 4D The ion guide 130 shown also has the advantage of being robust to contamination. Figures 4A - 4D In the ion guide 130 shown, there is no ion guide rod electrode 131 on the passage of the gas flow flowing along the central axis AC. Therefore, droplets and the like that cause contamination are not easily collided with the ion guide rod electrode 131, so the ion guide 130 is robust to contamination. In addition, since the surface area of the ion guide rod electrode 131 is large, even if a part of the electrode is contaminated, the electric field is not easily affected. Therefore, the ion guide 130 is robust to contamination.

[0068] <Relationship between the distance in the ion guide 130 and the voltage on the central axis AC>

[0069] Figure 5 is a graph showing the relationship between the distance in the ion guide 130 obtained by simulation and the voltage on the central axis AC. The voltage on the central axis AC is the voltage defined by the axial electric field. Thus, the voltage on the central axis AC generally does not coincide with the acceleration voltage.

[0070] Figure 5 In, the horizontal axis represents the position of the central axis AC (the position on the central axis) (i.e., the distance in the ion guide 130) (unit: cm), and the vertical axis represents the voltage on the central axis AC (the voltage on the central axis). In addition, in the horizontal axis, zero represents the position of the ion source 151. In addition, P1 represents the inlet of the ion guide 130, and the reference numeral 401 represents the cooling section.

[0071] Figure 4C 、 Figure 4DThe difference between the shown distance Da and distance Db is the largest at the entrance of the ion guide 130. That is, the voltage applied to the central axis AC is also the highest at the entrance of the ion guide 130. Then, as described above, as the distance from the entrance of the ion guide 130 increases, the difference between distance Da and distance Db decreases. Therefore, as the distance from the entrance of the ion guide 130 increases, the voltage applied to the central axis AC gradually decreases and becomes zero in the cooling section 401 near the exit of the ion guide 130. As described above, by applying an acceleration voltage to Figures 4A - 4D the shown ion guide 130, an axial electric field that continuously accelerates or decelerates ions is generated on the central axis AC.

[0072] In the ion guide 130, the kinetic energy of ions is cooled by collision with residual gas molecules and converged. The kinetic energy in the direction of the central axis AC is also cooled by collision with residual gas molecules. Therefore, when the acceleration voltage is zero, the ions temporarily stay inside the ion guide 130 and are pushed out by the electric repulsive force from the newly introduced ions at the entrance of the ion guide 130, and thus pass through the ion guide 130. Therefore, in a state where the applied acceleration voltage is zero, it takes about several ms to several hundreds of ms for the ions to pass through the ion guide 130.

[0073] Here, when the acceleration voltage is not zero, the moving speed of the ions in the ion guide 130 is given by the following formula (2).

[0074] V = KE……(2)

[0075] Here, K is the ion mobility and E is the axial electric field.

[0076] Figure 6 is a graph showing the relationship between the ion guide passage time of ions obtained by simulation and the ion amount.

[0077] Figure 6 In, the horizontal axis is the ion guide passage time (Time) and the vertical axis is the ion amount (Ion Counts).

[0078] In addition, the reference sign G1 represents the case where an acceleration voltage of 1V is applied, the reference sign G2 represents the case where an acceleration voltage of 3V is applied, and the reference sign G3 represents the case where an acceleration voltage of 5V is applied. In addition, the reference sign G4 represents the case where an acceleration voltage of 10V is applied, and the reference sign G5 represents the case where an acceleration voltage of 15V is applied.

[0079] According to Figure 6, it can be seen that the higher the acceleration voltage applied, the more concentrated the distribution of the ion amount is in a shorter ion guide passage time. Thus, the greater the acceleration voltage and the stronger the axial electric field, the faster the ions move and the shorter the time for the ions to pass through the ion guide 130. The ion mobility K can be approximately given by the following equation (3).

[0080] [Equation 2]

[0081]

[0082] Here, σ is the collision cross-sectional area of the ions, k is the Boltzmann constant, n is the density of gas molecules, Z is the charge of the ions, μ is the reduced mass of the ions, and T is the absolute temperature. The smaller the collision cross-sectional area σ, the faster the ions move and the shorter the time for the ions to pass through the ion guide 130. The collision cross-sectional area σ is determined by the size of the ions, but generally, ions with a higher m / z tend to have a larger collision cross-sectional area.

[0083] In Figure 7 , a graph showing the horizontal axis as the q-axis and the vertical axis as the a-value is shown for the stable region R10 in the ion guide 130. Here, the a-value and the q-value are respectively given by the following equations (4) and (5).

[0084] [Equation 3]

[0085]

[0086] [Equation 4]

[0087]

[0088] Here, e is the elementary charge amount, Z is the charge of the ions, m is the mass of the ions, Ω is the angular frequency of the RF voltage applied to the ion guide 130, V is the amplitude of the RF voltage applied to the ion guide 130, and r0 is the inscribed circle range of the ion guide 130. In addition, U is the value of the DC voltage applied to the rod electrode 131 of the ion guide, and 2U is the acceleration voltage.

[0089] Ions that can perform stable orbital motion in the ion guide 130 are limited to Figure 7 ions within the region of the stable region R10, and ions outside the region of the stable region R10 are excluded from the ion guide 130. As Figure 1 , Figure 2A and Figure 2B show, in the structure where the RF voltage of the ion guide 130 depends on the voltage of the quadrupole mass filter 140, when an acceleration voltage is applied, the ends of the stable region R10 are q 1 q 2When it comes to the m / z range of ions that can pass through the ion guide 130, using the m / z of the ions measured by the mass analyzer 100, i.e., m', and the ratio α of the amplitude of the RF voltage of the quadrupole mass filter 140 to that of the ion guide 130, the following formula (6) is obtained.

[0090] [Mathematical formula 5]

[0091]

[0092] Here, r 0 is the inscribed circle radius of the ion guide 130, r' 0 is the inscribed circle radius of the quadrupole mass filter 140, and q' is the q value of the ions measured by the mass analyzer 100, usually 0.7.

[0093] As shown in formula (6), the m / z range of ions that can pass through the ion guide 130 also changes depending on the m / z of the ions measured by the mass analyzer 100.

[0094] <Ion signal amount at m / z switching>

[0095] Here, referring to Figure 8 , consider the operation of switching the m / z measured by the mass analyzer 100 from m1 to m2.

[0096] Figure 8 is a schematic diagram showing the ion signal amount when switching m / z from m1 to m2.

[0097] Figure 8 In, the upper part shows the ion signal amount when m / z is m1, and the lower part shows the ion signal amount when m / z is m2. In the upper and lower diagrams, the horizontal axis represents time, and the vertical axis represents the ion signal amount.

[0098] For the case of ions with m / z = m1 measured by the mass analyzer 100, the explanation is made with reference to the upper part. Then, under such conditions, for the case where ions with m / z = m2 are outside the stable region R10 (refer to Figure 7 ) of the ion guide 130 having the ion mobility shown in formula (2). During the time when the mass analyzer 100 measures ions with m / z = m1, ions with m / z = m2 are excluded from the inside of the ion guide 130. Therefore, as Figure 8As shown schematically in the lower part, after switching the m / z measured by the mass analyzer 100 to m2, ions with m / z of m2 were not immediately observed. Then, after a delay time Td, the ion signal with m / z of m2 increased. This delay time Td is the time required for ions with m / z of m2 to reach the quadrupole mass filter 140 through the ion guide 130. In order to shorten the delay time Td and reduce the loss of ion signals (delay during switching), it is necessary to set the acceleration voltage to a higher value to increase the moving speed of ions in the ion guide 130.

[0099] <Control Method>

[0100] Figure 9 It is a diagram showing the control method of the mass analysis system 1 of the first embodiment.

[0101] In the control region RA represented by a parallelogram, the left line L11 is defined by q1 in Equation (6), and the right line L12 is defined by the ion mobility. In addition, the upper side L13 of the control region RA is defined by the upper limit of the acceleration voltage in the mass analyzer 100. In addition, the lower side L14 of the control region RA indicates that the acceleration voltage is zero.

[0102] Figure 9 The region RB1 is a region where the time from switching the m / z measured by the mass analyzer 100 until the ions reach the quadrupole mass filter 140 is long, and the loss (delay) of ions during switching is large. Because it is a high m / z, and the higher the ions, the slower the moving speed under the same electric field acceleration according to Equations (2) and (3), a higher acceleration voltage is required to suppress the loss (delay) of ion signals. Here, q1 is Figure 7 The lower limit value of the stable region R10 where ions stably pass through in the ion guide 130 shown.

[0103] On the other hand, Figure 9 The region RB2 is a region where the ions measured by the mass analyzer 100 are outside the stable region R10 (refer to Figure 7 ) in the ion guide 130 and no ions are observed. According to Figure 7 It can be seen that the lower the m / z of the ions, the easier it is to be outside the region of the stable region R10 at a lower acceleration voltage.

[0104] In the past, as shown by line L31, the acceleration voltage was fixed for measurement. When switching ions, measurement was performed in a state where the acceleration voltage was fixed to the acceleration voltage suitable for the ions after switching. In this way, at a certain acceleration voltage, it is impossible to balance the acceleration voltage at which low m / z ions can stably pass through the ion guide 130 and the acceleration voltage at which high m / z ions can pass through without loss (delay) during m / z switching. Therefore, the m / z range of ions that can pass through the ion guide 130 without loss (delay) is limited to Figure 7 the range shown in Figure 9 the range indicated by symbol C1 in

[0105] Figure 9 The control line L21 in Figure 3 is an example of the control of the acceleration voltage in the present embodiment. As shown by the control line L21, the voltage control device 200 controls the acceleration voltage. In addition, the control line L21 corresponds to

[0106] the scan line L1 in Figure 9 That is, when the m / z of the ions measured by the mass analyzer 100 is relatively low, the voltage control device 200 controls the acceleration voltage to a relatively low value. In addition, when the m / z of the ions measured by the mass analyzer 100 is relatively high, the voltage control device 200 sets the acceleration voltage to a relatively high value. Specifically, as shown by the control line L21 in Figure 9 it is preferable to control the acceleration voltage in such a way that it is proportional to the m / z. By doing so, the value of a in the ion guide 130 for ions with m / z measured by the mass analyzer 100 can be made a fixed value passing through the stable region R10 (refer to Figure 7 ).

[0107] In addition, the control of the acceleration voltage may not depend on the m / z as shown by the control line L21 in Figure 9 . As long as the relationship between the acceleration voltage and the m / z is inside the control region RA and the acceleration voltage increases as the m / z increases. For example, it may not be the case that the acceleration voltage changes continuously as shown by the control line L21 in Figure 9 , but may change stepwise, for example. Or, the voltage control device 200 may also change the acceleration voltage linearly at a specified slope to a specified m / z, and in the region of m / z greater than the specified m / z, change the acceleration voltage linearly at another slope.

[0108] As in Figure 9As shown by the control line L21, control is performed in such a manner that the acceleration voltage is proportional to m / z. Ions with low m / z can stably pass through the ion guide 130, and ions with high m / z can also pass through without loss (delay) during m / z switching. As described above, by using the control method of the present embodiment, as shown by reference numeral C2, ions in a wider m / z range can pass through without loss (delay) compared to the conventional control method using a fixed acceleration voltage.

[0109] That is, by applying a higher acceleration voltage to ions with slow moving speed (low ion mobility) and large m / z, the moving speed is increased. Thus, during m / z switching, even when switching to ions with large m / z, loss (delay) can be reduced. Additionally, Figure 9 in the region of low m / z, the control line L21 is a region lower than the line L31 in the conventional control. That is, in the region of low m / z, an acceleration voltage lower than that in the conventional control is applied. However, ions with low m / z originally have high ion mobility and sufficient moving speed even at a lower acceleration voltage. Thus, in the region of low m / z, there is no problem even if an acceleration voltage lower than that in the conventional control is applied. That is, the greater the m / z, the greater the effect of the present embodiment.

[0110] [Second Embodiment]

[0111] <Control Method>

[0112] Refer to Figure 10 to describe the control method of the acceleration voltage in the second embodiment.

[0113] Figure 10 is a diagram showing the control method of the mass analysis system 1 of the second embodiment. Figure 10 In Figure 9 the same structure is assigned the same reference numeral and description thereof is omitted.

[0114] Additionally, since the structure of the mass analysis device 100 in the second embodiment is the same as that Figure 1 shown, description thereof is omitted here.

[0115] When the mass of the residual gas molecules in the ion guide 130 is sufficiently small compared to the mass of the ions, the reduced mass μ in Equation (3) can be approximated as the mass m of the ions. Additionally, assuming that the shape of the ions is approximately spherical and the density is uniform, the collision cross-sectional area σ of the ions in Equation (3) is proportional to the 2 / 3 power of the mass of the ions. When using this approximate relationship, the ion mobility K in Equation (3) becomes the following Equation (7).

[0116] [Mathematical Formula 6]

[0117]

[0118] In formula (7), as described above, K represents the ion mobility.

[0119] The voltage control device 200 obtains the acceleration voltage based on the relational expression of formula (7). For example, when the length L of the ion guide 130 is sufficiently large relative to the length of the cooling section 401, the relationship between the time t for a monovalent ion to pass through the ion guide 130 and the acceleration voltage 2U can be written as the following formula (8) using the K in formula (7) and the proportionality constant C uniquely determined by the structure of the ion guide.

[0120] [Mathematical formula 7]

[0121]

[0122] According to formula (8), in the case of first-order ions, by controlling the acceleration voltage in a manner proportional to the 5 / 6 power of the mass of the ions, ions in a relatively wide m / z range can pass through the ion guide 130 in time t. The control line L22 is the control line of the acceleration voltage obtained based on the relational expression of formula (7).

[0123] By doing so, the influence of residual gas molecules in the ion guide 130 can be excluded, so that the time for ions to pass through the ion guide 130 can be controlled to be approximately fixed. That is, the control method of the second embodiment can control the time for ions to pass through the ion guide 130 with higher precision.

[0124] [Third Embodiment]

[0125] Next, refer to Figure 11 and Figure 12 to describe the third embodiment of the present invention.

[0126] <Mass spectrometry system 1a>

[0127] Figure 11 is the structural diagram of the mass spectrometry system 1a of the third embodiment.

[0128] Figure 11 The structure of the mass spectrometry system 1a shown has a storage device 310 connected to the voltage control device 200, which is different from the mass spectrometry system 1 shown in Figure 1 The storage device 310 stores a table of the relationship between the acceleration voltage and m / z. The table will be described later. In addition, the storage device 310 can also be provided in the cloud or the like.

[0129] <Control method>

[0130] Figure 12 is a diagram showing the control method of the mass spectrometry system 1a of the third embodiment.

[0131] The data point P is a plotting point representing the relationship between the acceleration voltage measured in the past and m / z. The data point P can be measured in advance for each m / z of ions and determined experimentally in such a way that the ion signal intensity is maximized when switching m / z. The data point P is held as a table in the storage device 310.

[0132] Then, the control line L23 located between the data points P is generated by linearly interpolating the data points P. The voltage control device 200 controls the acceleration voltage according to Figure 12 the control line L23 shown.

[0133] <Flowchart>

[0134] Figure 13 This is a flowchart showing the flow of the control method of the mass analysis system 1a of the third embodiment. Appropriate reference is made to Figure 12 .

[0135] First, ions are measured with the mass analysis device 100, and the voltage control device 200 stores the m / z and acceleration voltage used in the measurement in the storage device 310 (S101).

[0136] Next, the voltage control device 200 plots the acceleration voltage and m / z stored in the storage device 310 as data points P in the coordinates shown in Figure 12 . (S102)

[0137] Then, the voltage control device 200 performs linear interpolation on the control line L23 (S103).

[0138] After that, the voltage control device 200 controls the acceleration voltage along the control line L23 (S104).

[0139] Strictly speaking, the ion mobility K depends not only on m / z but also on the molecular structure. Therefore, by generating a table of acceleration voltage and m / z using the sample to be measured or a compound having a structure similar to that of the sample and controlling the acceleration voltage, it is possible to perform acceleration voltage control that conforms to the actual situation. That is, it is possible to perform acceleration voltage control considering the molecular structure. As a result, it is possible to further reduce the loss (delay) of the ion signal when switching the m / z measured by the mass analysis device 100 compared to other embodiments.

[0140] [Fourth Embodiment]

[0141] Next, with reference to Figure 14A and Figure 14B , the fourth embodiment of the present invention will be described.

[0142] Among them, in the fourth embodiment, the structure of the mass analysis system 1 is the same as that of Figure 1Since it is the same as that shown, the illustration and description here are omitted.

[0143] Figure 14A It is a graph showing the time variation of the acceleration voltage. Figure 14B It is a graph showing the time variation of the m / z of the ions measured by the mass analysis system 1.

[0144] In addition, Figure 14A and Figure 14B At times t0 to t5 represent the same time.

[0145] The loss (delay) of the ion signal when switching the m / z measured by the mass analysis device 100 depends on Figure 8 The difference in m / z between the ion with m / z of m1 and the ion with m / z of m2 as shown. When measuring the ion with m / z of m1, if the ion with m / z of m2 can stably exist in the ion guide 130, the delay time Td (refer to Figure 8 ) is zero, and no loss (delay) of the ion signal occurs.

[0146] Generally, in the measurement using the quadrupole mass analysis device as the mass analysis device 100, as Figure 14B shown, the m / z measured by the mass analysis device 100 is switched at regular intervals to measure various ions. In the fourth embodiment, when the m / z of the ion to be measured next is m n and can stably pass through the ion guide 130 under the measurement conditions of the ion with m / z of m n-1 measured just before, that is, when the difference Δm in m / z of the ion measured just before (=m n -m n-1 ) is small ( Figure 14B 's Δma), as Figure 14A shown, the control device sets the acceleration voltage to zero or a sufficiently low value. In addition, when the ion with m / z of m n to be measured next cannot stably pass through the ion guide 130 under the measurement conditions of the ion with m / z of m n-1 measured just before, that is, when Δm is large ( Figure 14B 's Δmb), an acceleration voltage corresponding to the m / z is applied.

[0147] In short, when the difference in m / z (Δm) is less than a specified value (Δma), even if a new acceleration voltage is not applied, the ions to be measured reach the vicinity of the outlet of the ion guide 130 due to the previously applied acceleration voltage. Therefore, ion measurement can be performed without applying an acceleration voltage. In contrast, when the difference in m / z (Δm) is greater than the specified value (Δmb), the ions to be measured cannot pass through the ion guide 130 under the previously applied acceleration voltage. Therefore, a new acceleration voltage is applied.

[0148] When an acceleration voltage is applied, the radial distribution of ions near the outlet of the ion guide 130 expands, and the number of ions passing through the fine hole 123 decreases. However, in the fourth embodiment, a new acceleration voltage is not applied under the condition of a small Δm (Δma), so the expansion of the radial distribution of ions near the outlet of the ion guide 130 can be reduced. Thereby, highly sensitive measurement can be achieved. When the measurement order is arranged and measurement is performed in such a way that Δm is made as small as possible corresponding to the m / z of the ions to be measured, more ions can be measured with high sensitivity.

[0149] [Voltage control device 200]

[0150] Figure 15 is a functional block diagram showing the structure of the voltage control device 200 of the present embodiment.

[0151] The voltage control device 200 includes a memory 210, a CPU (Central Processing Unit) 201, input devices 202 such as a keyboard and a mouse, output devices 203 such as a display, DC power supplies 301 and 303, an RF power supply 302, and a communication device 204 that communicates with a storage device 310.

[0152] In the memory 210, a program stored in the storage device of the voltage control device 200 (not shown) is loaded, and the loaded program is executed by the CPU 201. Thereby, the voltage control unit 211 is implemented. The voltage control unit 211 performs operations as shown in Figure 9 , Figure 10 , Figure 12 , Figure 13 , and controls the acceleration voltage as shown in FIG. 14.

[0153] The present invention is not limited to the above embodiments and includes various modifications. For example, the above embodiments are described in detail for easy understanding of the present invention and are not limited to having all the structures described. In addition, a part of the structure of one embodiment can be replaced with the structure of another embodiment, and the structure of another embodiment can also be added to the structure of one embodiment. In addition, for a part of the structure of each embodiment, other structures can be added, deleted, or replaced.

[0154] In addition, for each of the above structures, functions, voltage control unit 211, storage device 310, etc., a part or all of them can be implemented in hardware, for example, by designing in an integrated circuit. In addition, as Figure 15 shown, each of the above structures, functions, etc. can also be implemented in software by a processor such as CPU 201 interpreting and executing a program that realizes each function. Information such as programs, tables, and files that realize each function can be stored not only in an HD (Hard Disk), but also in a recording device such as a memory or SSD (Solid State Drive), or a recording medium such as an IC (Integrated Circuit) card, SD (Secure Digital) card, or DVD (Digital Versatile Disc).

[0155] In addition, in each embodiment, the control lines and information lines show those considered necessary for explanation, and do not necessarily show all the control lines and information lines on the product. In fact, it can also be considered that almost all structures are interconnected.

[0156] Description of Reference Numerals

[0157] 1, 1a Mass analysis system

[0158] 100 Mass analyzer

[0159] 130 Ion guide

[0160] 131 Ion guide rod electrode

[0161] 131a, 131c Ion guide rod electrodes (a pair of ion guide rod electrodes)

[0162] 140 Quadrupole mass filter (mass filter)

[0163] 151 Ion source

[0164] 152 Detector

[0165] 302 RF power supply (power supply)

[0166] 303 DC power supply (power supply)

[0167] 310 Storage device

[0168] AC central axis

[0169] m / z Mass-to-charge ratio

[0170] L10 Stable region

[0171] L11 Line (lower limit value of the stable region)

[0172] L12 line (ion mobility)

[0173] L13 upper side (upper limit value of acceleration voltage)

[0174] L14 lower side (acceleration voltage is zero)

[0175] L21 control line (controls acceleration voltage)

[0176] L22 control line (controls acceleration voltage)

[0177] L23 control line (control line after linear interpolation)

[0178] P data point (plotting point)

[0179] R10 stable region

[0180] RA control region

[0181] 200 voltage control device (voltage control section)

[0182] 211 voltage control section.

Claims

1. A control method for a mass analysis device, characterized in that: it includes a mass analysis device, a power supply, and a voltage control unit, wherein the mass analysis device includes: an ion source for generating ions; an ion guide disposed at the subsequent stage of the ion source to converge the ions; a mass filter disposed at the subsequent stage of the ion guide to separate the ions converged by the ion guide according to the mass-to-charge ratio; and a detector disposed at the subsequent stage of the mass filter to detect the ions separated by the mass filter, the power supply includes a power supply for applying at least a first DC voltage to the ion guide, a power supply for applying at least a second DC voltage to the ion guide, and a power supply for applying an AC voltage biased by a DC voltage to the ion guide, the voltage control unit controls the acceleration voltage, which is the difference between the first DC voltage and the second DC voltage, by controlling the power supply, in a coordinate system where one coordinate axis represents the mass-to-charge ratio of the ions passing through the ion guide and the other coordinate axis represents the acceleration voltage applied to the ion guide, within a control region surrounded by the lower limit value of the stable region where the ions stably pass through the ion guide, the ion mobility of the ions, the upper limit value of the acceleration voltage, and the value where the acceleration voltage is zero, the voltage control unit controls the acceleration voltage such that the larger the mass-to-charge ratio of the measured ions, the larger the acceleration voltage.

2. The control method for a mass analysis device according to claim 1, characterized in that: the voltage control unit controls the acceleration voltage within the control region such that the acceleration voltage is proportional to the mass-to-charge ratio of the ions.

3. The control method for a mass analysis device according to claim 1, characterized in that: the voltage control unit controls the acceleration voltage to be inversely proportional to the 5 / 6 power of the mass of the ions.

4. The control method for a mass analysis device according to claim 1, characterized in that: the voltage control unit stores the acceleration voltage and the measured mass-to-charge ratio of the ions when the mass analysis device measures a specified ion multiple times in a storage device, in the coordinate system, performs plotting associating the acceleration voltage stored in the storage device with the mass-to-charge ratio, calculates a control line obtained by linearly interpolating between points in the coordinate system obtained by plotting, and controls the acceleration voltage along the calculated control line.

5. The control method for a mass analysis device according to claim 1, characterized in that: when the difference in the mass-to-charge ratio between a first ion to be measured next by the mass analysis device and a second ion measured one before the first ion is below a specified value, the voltage control unit does not apply the acceleration voltage when measuring the first ion.

6. A mass analysis system, characterized in that: it includes a mass analysis device, a power supply, and a voltage control unit, wherein the mass analysis device includes: an ion source for generating ions; An ion guide disposed downstream of the ion source to converge the ions; A mass filter disposed downstream of the ion guide to separate the ions converged by the ion guide according to the mass-to-charge ratio; and A detector disposed downstream of the mass filter to detect the ions separated by the mass filter, The power supply includes a power supply for applying at least a first DC voltage to the ion guide, a power supply for applying at least a second DC voltage to the ion guide, and a power supply for applying an AC voltage biased by a DC voltage to the ion guide, The voltage control unit controls the acceleration voltage, which is the difference between the first DC voltage and the second DC voltage, by controlling the power supply, In a coordinate system where one coordinate axis represents the mass-to-charge ratio of the ions passing through the ion guide and the other coordinate axis represents the acceleration voltage applied to the ion guide, the voltage control unit controls the acceleration voltage within a control region surrounded by the lower limit value of the stable region where the ions stably pass through the ion guide, the ion mobility of the ions, the upper limit value of the acceleration voltage, and the value where the acceleration voltage is zero, such that the larger the measured mass-to-charge ratio of the ions, the larger the acceleration voltage.

7. The mass analysis system according to claim 6, wherein: The ion guide has four ion guide rod electrodes, At least one pair of the ion guide rod electrodes forming the ion guide has a distance from the central axis of the ion guide that changes with the position on the central axis, The surface of the electrode whose distance from the central axis of the ion guide changes and faces the central axis of the ion guide is a plane.

8. A voltage control device in a mass analysis system, wherein the mass analysis system includes a mass analysis device, a power supply, and a voltage control unit, The mass analysis device comprises: An ion source that generates ions; An ion guide disposed downstream of the ion source to converge the ions; A mass filter disposed downstream of the ion guide to separate the ions converged by the ion guide according to the mass-to-charge ratio; and A detector disposed downstream of the mass filter to detect the ions separated by the mass filter, The power supply includes a power supply for applying at least a first DC voltage to the ion guide, a power supply for applying at least a second DC voltage to the ion guide, and a power supply for applying an AC voltage biased by a DC voltage to the ion guide, The voltage control unit controls the acceleration voltage, which is the difference between the first DC voltage and the second DC voltage, by controlling the power supply, The voltage control device is characterized in that: It has a voltage control unit that controls the acceleration voltage within a control region surrounded by the lower limit value of the stable region where the ions stably pass through the ion guide, the ion mobility of the ions, the upper limit value of the acceleration voltage, and the value where the acceleration voltage is zero, in coordinates where one coordinate axis represents the mass-to-charge ratio of the ions passing through the ion guide and the other coordinate axis represents the acceleration voltage applied to the ion guide, such that the larger the measured mass-to-charge ratio of the ions, the larger the acceleration voltage.

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