Ion trap mass spectrometer, mass spectrometry method, and computer readable medium storing control program

Abstract

The present invention relates to an ion trap mass spectrometer, comprising: an ion trap, comprising a first electrode and a second electrode different from the first electrode; a first voltage control unit, which periodically switches a DC voltage of multiple different values ​​and applies it to the first electrode; and a second voltage control unit, which applies a sinusoidal voltage to the second electrode when dissociating ions captured by the ion trap.

Description

Technical Field

[0001] The invention relates to an ion trap mass spectrometer, a mass spectrometry method and a non-transitory computer readable medium storing a control program. Background Art

[0002] Ions trapped in the ion trap are dissociated by an ion trap mass spectrometer, and the ions generated by the dissociation are mass separated and detected (see Patent Document 1). In an ion trap, ions are trapped by applying a voltage such as a sine wave or a rectangular wave to electrodes arranged around the space for trapping ions. In the case of a digital ion trap (DIT) that traps ions by applying a rectangular wave voltage, there are advantages such as easier frequency-modulated mass separation because a resonator is not required, and no high-voltage power supply for amplitude modulation is required (see Patent Document 2). The behavior of ions in an ion trap is studied by theory and simulation (see Non-Patent Documents 1, 2, and 3).

[0003] Prior art literature

[0004] Patent Literature

[0005] Patent Document 1: Japanese Patent Application Laid-Open No. 2001-210268

[0006] Patent Document 2: U.S. Patent No. 7193207

[0007] Non-patent literature

[0008] Non-patent document 1: Ding L, Sudakov M, Kumashiro S. "A simulation study of the digital ion trap mass spectrometer", International Journal of Mass Spectrometry, (Netherlands), Elsevier, November 15, 2002, Volume 221, Issue 2, pp. 117-138

[0009] Non-patent document 2: Konenkov NV, Sudakov M, Douglas DJ. "Matrix methods for the calculation of stability diagrams in quadrupole mass spectrometry", Journal of the American Society for Mass Spectrometry, (USA), Elsevier, June 2002, Volume 13, Issue 6, pp. 597-613

[0010] Non-patent document 3: Ding L, Sudakov M, Brancia FL, Giles R, Kumashiro S. "A digital ion trap mass spectrometer coupled with atmospheric pressure ion sources", Journal of mass spectrometry, (UK), Wiley, May 2004, Volume 39, Issue 5, pp. 471-84 Summary of the invention

[0011] Technical problem to be solved by the invention

[0012] When ions are dissociated using an ion trap, mass spectrometry with high accuracy can be performed.

[0013] Solutions for solving the above technical problems

[0014] The first scheme of the present invention relates to an ion trap mass spectrometer, comprising: an ion trap, comprising a first electrode and a second electrode different from the first electrode; a first voltage control unit, which periodically switches a DC voltage of multiple different values ​​and applies it to the first electrode; and a second voltage control unit, which applies a sinusoidal wave voltage to the second electrode when dissociating ions trapped by the ion trap.

[0015] The second scheme of the present invention relates to a mass spectrometry analysis method, which uses an ion trap mass spectrometer with an ion trap, wherein the ion trap has a first electrode and a second electrode different from the first electrode, and the mass spectrometry analysis method comprises: periodically switching a DC voltage of multiple different values ​​and applying it to the first electrode; and applying a sinusoidal voltage to the second electrode when dissociating ions trapped by the ion trap.

[0016] The third scheme of the present invention relates to a computer-readable medium storing a control program for causing a processing device to perform a process of controlling an ion trap mass spectrometer having an ion trap, wherein the ion trap has a first electrode and a second electrode different from the first electrode, and the process includes: a first voltage control process of periodically switching a DC voltage of multiple different values ​​and applying it to the first electrode; and a second voltage control process of applying a sinusoidal wave voltage to the second electrode when dissociating ions trapped by the ion trap, and the control program causes the computer to execute the process.

[0017] Effects of the Invention

[0018] According to the present invention, when ions are dissociated using an ion trap, mass spectrometry with high accuracy can be performed. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a conceptual diagram showing the structure of an ion trap mass spectrometer according to one embodiment.

[0020] Figure 2 It is a conceptual diagram showing the configuration of the information processing unit.

[0021] Figure 3 This is a conceptual diagram showing the waveform of a voltage applied to an electrode of an ion trap according to an embodiment.

[0022] Figure 4 This is a flowchart showing the flow of a mass spectrometry method according to one embodiment.

[0023] Figure 5 This is a conceptual diagram for explaining provision of a program.

[0024] Figure 6 This is the product ion spectrum of angiotensin II in Example 1.

[0025] Figure 7 This is the product ion spectrum of angiotensin II in Comparative Example 1.

[0026] Figure 8 This is the product ion spectrum of ACTH (18-39) in Example 2.

[0027] Fig. 9 This is the product ion spectrum of ACTH (18-39) in Comparative Example 2. DETAILED DESCRIPTION

[0028] Hereinafter, specific embodiments of the present invention will be described with reference to the accompanying drawings.

[0029] Figure 11 is a conceptual diagram showing the structure of the ion trap mass spectrometer of the present embodiment. The ion trap mass spectrometer 1 includes a measuring unit 100 and an information processing unit 40. The measuring unit 100 includes an ionization unit 10; an ion trap 20 for trapping ions S from a sample; a first voltage application unit 21; a second voltage application unit 22; a gas supply unit 23; and a detection unit 30. The ion trap 20 includes an end cap electrode 201, an annular electrode 202, an ion introduction port 203, and an ion ejection port 204. The end cap electrode 201 includes an inlet-side end cap electrode 201a and an outlet-side end cap electrode 201b. The first voltage application unit 21 includes a direct current (DC) power supply 211 and a switching unit 212. The gas supply unit 23 includes a gas supply source 230, a valve 231, and a gas introduction unit 232.

[0030] The measurement unit 100 analyzes the sample and outputs data obtained by measuring ions S derived from the sample to the information processing unit 40 .

[0031] The ionization unit 10 of the measurement unit 100 is configured with an ion source, and ionizes molecules contained in the sample. The ionization method is not particularly limited, and for example, matrix assisted laser desorption / ionization (MALD I) or electrospray ionization (ESI) can be used. The ions S derived from the sample generated by ionization of the ionization unit 10 move according to electromagnetic action based on a voltage applied to an electrode not shown in the figure, and are introduced into the ion trap 20 (arrow A1) through the ion introduction port 203 provided on the entrance side end cap electrode 201a.

[0032] The ion trap 20 of this embodiment is a three-dimensional quadrupole ion trap. Ions S from the sample introduced from the ion introduction port 203 are trapped in the space Sp surrounded by the end cap electrode 201 and the annular electrode 202. The end cap electrode 201 and the annular electrode 202 are rotationally symmetric with respect to the central axis Ax, and preferably, the surfaces of the end cap electrode 201 and the annular electrode 202 that are opposite to the space Sp are formed to be hyperbolic in the cross section containing the central axis Ax.

[0033] The type and shape of the ion trap 20 are not particularly limited as long as the ion trap 20 includes a plurality of electrodes and can trap ions inside the ion trap 20 by applying a voltage from the first voltage application unit 21 to at least one of the electrodes. For example, the ion trap 20 may be a linear ion trap.

[0034] The first voltage applying unit 21 applies a rectangular wave voltage to the annular electrode 202. The DC power supply 211 includes at least one voltage source configured to output a plurality of DC voltages of different values. The switching unit 212 includes a switching element such as a MOSFET (Metal-Oxide-Semiconductor Field-Effect Transistor), switches the plurality of DC voltages of different values ​​and applies them to the annular electrode 202. The switching unit 212 periodically switches two DC voltages of different values ​​at a predetermined frequency and applies them to the annular electrode 202, thereby applying a rectangular wave to the annular electrode 202.

[0035] As long as the precursor ions to be dissociated can be captured, the amplitude of the rectangular wave applied by the first voltage application unit 21 to the annular electrode 202 is not particularly limited. For example, the difference between the voltage on the high voltage side and the voltage on the low voltage side of the rectangular wave, or the difference between the two voltages output by the DC power supply 211, is preferably 400V to 2kV.

[0036] As will be described later, the frequency of the rectangular wave applied by the first voltage applying unit 21 to the annular electrode 202 is controlled by the first voltage control unit 511 ( Figure 2 The frequency of the rectangular wave, in other words, the frequency of the DC voltage switched by the switching unit 212 is set based on the m / z (corresponding to the mass-to-charge ratio) of the precursor ions contained in the ions S derived from the sample, etc.

[0037] The second voltage applying unit 22 controls the voltage of the second voltage control unit 512 ( Figure 2 ) is controlled to apply a sinusoidal voltage to the end cap electrode 201. The second voltage applying unit 22 has a digital / analog (D / A) converter. When performing dissociation, the second voltage control unit 512 outputs a sinusoidal digital signal to the second voltage applying unit 22. The dissociation is collision-induced dissociation (CID). The second voltage applying unit 22 converts the digital signal into an analog sinusoidal voltage through the D / A converter and applies it to one of the inlet-side end cap electrode 201a and the outlet-side end cap electrode 201b, and applies a voltage of antiphase to the sinusoidal voltage to the other.

[0038] In addition, as long as a sinusoidal voltage can be applied to the annular electrode 202 , the configuration of the second voltage applying unit 22 is not particularly limited, and a sinusoidal wave may be generated using an analog circuit without performing D / A conversion.

[0039] As described in detail later, the frequency of the sine wave applied by the second voltage applying unit 22 to the end cap electrode 201 is preferably based on the secular frequency of the precursor ions. The amplitude of the sine wave is not particularly limited as long as dissociation is performed with desired accuracy, and can be 0.1V to 2.0V.

[0040] Figure 3 2 is a conceptual diagram schematically showing the waveforms of the voltages applied to the end cap electrode 201 and the ring electrode 202. In the graphs showing the waveforms W1, W21, and W22, the vertical axis is the voltage value of the electrode and the horizontal axis is time. Figure 3 , the correspondence between the waveforms W21 , W1 , and W22 and the electrodes to which the voltages of the waveforms are applied is schematically shown by arrows A31 , A32 , and A33 .

[0041] The waveform W1 shows the waveform of the rectangular wave applied by the first voltage applying unit 21 to the annular electrode 202. The voltage value on the high voltage side of the rectangular wave is set to +HV, and the voltage value on the low voltage side is set to -HV. The waveforms W21 and W22 respectively show the waveforms of the voltage applied to the outlet end cap electrode 201b and the inlet end cap electrode 201a. The maximum value of the voltage in the sine wave is set to +EV, and the minimum value is set to -EV. The ions S from the sample are resonantly excited by the electric field and magnetic field generated in the space Sp by the voltage applied by the second voltage applying unit 22 to the end cap electrode 201, and collide with the molecules contained in the CID gas described later, thereby being dissociated.

[0042] The ion trap 20 can selectively capture or discharge ions S from the sample based on their m / z. For example, in the ion trap 20, after capturing ions above a specified m / z by low mass cutoff (LMCO), the second voltage application unit 22 can separate precursor ions (also assumed to be multiple ions) by applying a FNF (Filtered Noise Field) signal or a SWIFT (Stored Wave Inverse Fourier Transform) signal to the end cap electrode 201.

[0043] The ion trap 20 can eject the ions S from the sample from the ion ejection port 204 while mass-separating them by resonant excitation ejection. In the resonant excitation ejection, in synchronization with the frequency of the rectangular wave voltage applied to the annular electrode 202, a rectangular wave voltage having a frequency obtained by frequency-dividing the rectangular wave voltage is appropriately applied to the end cap electrode 201 by the second voltage applying unit 22. In this state, the first voltage applying unit 21 sweeps the frequency in a direction that reduces the frequency of the rectangular wave voltage applied to the annular electrode 202. Thus, the ions are selectively resonantly excited in sequence from the ions with lower m / z to the ions with higher m / z, and are ejected from the ion trap 20 while being mass-separated. Alternatively, in the above state, the first voltage applying unit 21 sweeps the frequency in a direction that increases the frequency of the rectangular wave voltage applied to the annular electrode 202. Thus, the ions are selectively resonantly excited in sequence from the ions with higher m / z to the ions with lower m / z, and are ejected from the ion trap 20 while being mass-separated.

[0044] return Figure 1 The sample-derived ions S including the product ions generated by dissociation in the ion trap 20 are ejected from the ion trap 20 by resonance excitation. The sample-derived ions S ejected from the ion trap 20 enter the detection unit 30 (arrow A2).

[0045] The gas supply unit 23 supplies cooling gas and CID gas to the ion trap 20. The gas supply source 230 includes a cooling gas storage container (not shown) containing a cooling gas such as helium and a CID gas storage container (not shown) containing a CID gas such as argon. The composition of the cooling gas and the CID gas is not particularly limited. The introduction of the cooling gas and the CID gas is arranged in the middle of the pipeline of these gases, and is controlled by the opening and closing of the valve 231 controlled by the device control unit 51 described later. The gas introduction unit 232 includes a pipeline extending to the ion trap 20, and preferably the cooling gas and the CID gas are introduced into the ion trap 20 via the pipeline.

[0046] In addition, Figure 1 Although only one pipeline is shown as the gas introduction part 232 , the cooling gas and the CID gas can be introduced into the ion trap 20 through a plurality of different pipelines.

[0047] The detection unit 30 is equipped with an ion detector, which includes a conversion dynode and a secondary electron multiplier tube, etc., to detect ions and appropriately multiply the detection signal generated by the detection. In the detection unit 30, the incident ions S originating from the sample are detected. The data obtained by the detection of the detection unit 30 is called measurement data. The detection signal generated by the detection is converted into an analog / digital (Analog / Digital; A / D) converter (not shown), and is output as measurement data to the information processing unit 40 (arrow A3), and is appropriately stored in the storage unit 43, etc.

[0048] Figure 2 : is a conceptual diagram showing the structure of the information processing unit 40. The information processing unit 40 includes an input unit 41, a communication unit 42, a storage unit 43, an output unit 44, and a control unit 50. The control unit 50 includes a device control unit 51, a data processing unit 52, and an output control unit 53. The device control unit 51 includes a first voltage control unit 511 and a second voltage control unit 512. Figure 1 In FIG. 1 , the control of the measuring unit 100 by the device control unit 51 is schematically shown by arrow A4.

[0049] The information processing unit 40 includes an information processing device such as an electronic computer, and appropriately serves as an interface with a user of the ion trap mass spectrometer 1 (hereinafter referred to as a user), and also performs processes such as communication, storage, and calculation related to various data.

[0050] In addition, the information processing unit 40 may be configured as one device integrated with the measuring unit 100. In addition, part of the data used by the ion trap mass spectrometer 1 may be stored in a remote server or the like.

[0051] The input unit 41 of the information processing unit 40 includes an input device such as a mouse, a keyboard, various buttons or a touch panel, etc. The input unit 41 receives information required for controlling the operation of the measurement unit 100 and information required for processing by the control unit 50 from the user.

[0052] The communication unit 42 of the information processing unit 40 is configured to include a communication device capable of communicating via a network such as the Internet by wireless or wired connection. The communication unit 42 transmits and receives appropriate necessary data.

[0053] The storage unit 43 of the information processing unit 40 is composed of a nonvolatile storage medium, and stores analysis conditions, measurement data, and a program for the control unit 50 to execute processing.

[0054] The output unit 44 of the information processing unit 40 includes a display such as a liquid crystal display or a printer, and displays information related to the measurement of the measuring unit 100 or information obtained by the processing of the data processing unit 52 on the display or prints it on a paper medium.

[0055] The control unit 50 of the information processing unit 40 is configured to include a processor such as a central processing unit (CPU) and a storage medium such as a memory, and functions as a main body for controlling the operation of the ion trap mass spectrometer 1. The control unit 50 is a processing device that performs processing such as controlling the voltage applied to each electrode of the ion trap 20. The control unit 50 holds the program stored in the storage unit 43 and the like in the memory, and the processor performs various processes by executing the program.

[0056] In addition, as long as the control unit 50 of this embodiment can perform processing, the physical structure of the control unit 50 is not particularly limited.

[0057] The device control unit 51 of the control unit 50 controls the operation of each unit of the measurement unit 100 based on information on analysis conditions based on input from the input unit 41 and the like and information stored in the storage unit 43 .

[0058] The first voltage applying unit 21 ( Figure 1 ) is set to Ω, and the angular frequency of the sine wave applied by the second voltage applying unit 22 to the end cap electrode 201 is set to ω. The device control unit 51 sets the angular frequency Ω of the rectangular wave and the angular frequency ω of the sine wave according to the m / z of the precursor ion set based on the user's input, etc.

[0059] Alternatively, the user may directly input the angular frequency Ω of the rectangular wave and the angular frequency ω of the sine wave via the input unit 41 .

[0060] The device control unit 51 obtains the m / z of the precursor ion input by the user. Alternatively, the device control unit 51 can also automatically detect a peak with a large peak intensity or peak area from data corresponding to a mass spectrum obtained by mass separation of an ionized sample without dissociation (hereinafter referred to as MS1 mass spectrum data), thereby obtaining the m / z corresponding to the peak. Here, in the MS1 mass spectrum data, the m / z is associated with the intensity of the detected ion having the m / z. The peak intensity is the maximum intensity of the peak, and the peak area is the area of ​​the peak.

[0061] The behavior of ions is described by the Matthew equation. In the Matthew equation, the stability of ions is evaluated by parameters a and q. If the average value of the rectangular wave voltage is set to U, the amplitude of the rectangular wave voltage (half the difference between the maximum and minimum voltages) is set to V, and the inscribed radius of the annular electrode 202 is set to r0, the parameters a and q are respectively expressed by the following equations (1) and (2) (see non-patent document 3).

[0062] a=8U / ((m / z)(r0) 2 Ω 2 )…(1)

[0063] q=4V / ((m / z)(r0) 2 Ω 2 )…(2)

[0064] If the average value U of the voltage applied to the annular electrode 202 is set to 0, the parameter a is 0. At this time, the maximum value q0 of q that satisfies the stability condition derived from the Matthew equation is 0.7125. Therefore, if the m / z that becomes the threshold value of LMCO is (m / z) LMCO , set the m / z of the precursor ion to (m / z) PRE , then according to formula (2), it is derived that there is a relationship between them as shown by the following formula (3).

[0065] q / q0=(m / z) LMCO / (m / z) PRE …(3)

[0066] If the ratio of m / z serving as a threshold value of LMCO to the m / z of the precursor ion is set in advance, the device control unit 51 can calculate the parameter q of the precursor ion according to equation (3).

[0067] Alternatively, the device control unit 51 may be configured to set the ratio of the m / z serving as the threshold value of LMCO to the m / z of the precursor ion based on the user's input.

[0068] Let the m / z on the right side of equation (2) be (m / z) PRE The device control unit 51 can adjust the amplitude V of the rectangular wave according to the calculated parameter q and the m / z of the precursor ion (m / z) PRE , use formula (2) to calculate the angular frequency Ω of the rectangular wave.

[0069] If the long-term frequency associated with the resonant excitation of the ion is set to ω s , then ω s It is calculated by the following formula (4) using the parameter β.

[0070] ω s =βΩ / 2…(4)

[0071] Here, the parameter β is calculated by the following formula (5) (see Non-Patent Document 3).

[0072] β=arccos(cos(π(q / 2) 0.5 )cosh(π(q / 2) 0.5 )) / π…(5)

[0073] Therefore, the device control unit 51 can calculate the parameter β of the precursor ion by equation (5) based on the parameter q calculated above, and calculate the long-term frequency ω of the precursor ion based on the parameter β and the angular frequency Ω of the rectangular wave calculated above. s .

[0074] In addition, the order in which the device control unit 51 calculates the above-mentioned parameters q and β, and the angular frequency Ω of the rectangular wave, etc. is not particularly limited. In addition, the values ​​of the above-calculated angular frequency ω, etc. can also be adjusted using correction data obtained through appropriate actual measurements. Furthermore, even when the parameter a is not 0, the device control unit 51 can calculate the long-term frequency ω using the Matthew equation and data related to the stability of the parameters a and q. s .

[0075] The first voltage control unit 511 of the device control unit 51 controls the first voltage application unit 21 to apply a voltage to the annular electrode 202. After the ions S from the sample are introduced into the ion trap 20, the first voltage control unit 511 controls the switching unit 212 to switch the DC voltage output from the DC power supply 211 at a frequency equivalent to the angular frequency Ω (Ω / 2π if the switching from high voltage to low voltage and the switching from low voltage to high voltage are set as one set). As a result, a rectangular wave voltage is applied to the annular electrode 202.

[0076] The switching frequency performed by the switching unit 212 may allow a difference of plus or minus 5% or the like from a frequency equivalent to the appropriate angular frequency Ω.

[0077] The second voltage control unit 512 of the device control unit 51 controls the second voltage application unit 22 to apply a sinusoidal voltage to the end cap electrode 201. The second voltage control unit 512 preferably applies a single sinusoidal wave of a predetermined angular frequency ω to the end cap electrode 201. Theoretically, from the perspective of efficiently performing resonance excitation, it is preferred to set the angular frequency ω of the sinusoidal wave to the long-term frequency ω. s However, due to the change in the waveform of the rectangular wave caused by stray capacitance of the circuit constituting the first voltage applying unit 21 or the influence of the deceleration of ions caused by the collision of the CID gas, the second voltage control unit 512 can set the angular frequency ω of the sine wave to be based on the long-term frequency ω. sThe second voltage control unit 512 can set the angular frequency ω of the sine wave to the long-term frequency ω. s The angular frequency is set to be 95% or more and less than 105%, preferably 97% or more and less than 103%.

[0078] The second voltage control unit 512 controls the operation of each unit of the measurement unit 100 according to the analysis conditions set by the user input, etc., and outputs a digital signal of a sine wave of an angular frequency ω to the second voltage application unit 22 during dissociation. The second voltage control unit 512 controls the second voltage application unit 22 to perform D / A conversion on the digital signal and apply it to the end cap electrode 201 (see Figure 3 ).

[0079] The second voltage control unit 512 preferably applies a sinusoidal voltage to the end cap electrode 201 when the m / z of the precursor ion is 2500 or more, more preferably 2400 or more, further preferably 1100 or more, and further preferably 1000 or more. The second voltage control unit 512 may also make the waveform of the voltage applied to the end cap electrode 201 via the second voltage application unit 22 different based on the m / z value of the precursor ion. Here, "making the waveform different" refers to a change in the shape of the waveform, and does not include a change in period or amplitude. For example, when the m / z of the precursor ion is greater than a specified threshold value such as 2500, 2400, 1100 or 1000, the second voltage control unit 512 applies a sinusoidal voltage to the end cap electrode 201. When the m / z of the precursor ion is below a specified threshold value, the second voltage control unit 512 can apply a rectangular wave voltage of a frequency other than a sine wave to the end cap electrode 201 after frequency division of the above-mentioned rectangular wave voltage.

[0080] The data processing unit 52 of the control unit 50 performs analysis processing on the measurement data output from the detection unit 30. The data processing unit 52 generates data corresponding to a mass spectrum that associates m / z with the intensity of the detected ions having the m / z based on the measurement data. The data processing unit 52 can generate data corresponding to a mass spectrum, i.e., a product ion spectrum, containing peaks of product ions of ions S derived from the sample obtained by the above dissociation. The data processing method performed by the data processing unit 52 is not particularly limited, and identification or quantification of molecules corresponding to the above peaks can be appropriately performed.

[0081] The output control unit 53 of the control unit 50 generates an output image showing the product ion spectrum generated by the data processing unit 52 or the analysis conditions of the measurement unit 100, outputs it to the output unit 44, and causes the output unit 44 to display it on a display.

[0082] Figure 4: is a flowchart showing the flow of the mass spectrometry method of this embodiment. In step S101, the device control unit 51 controls the ionization unit 10 to ionize the sample to generate ions S derived from the sample. After step S101 is completed, step S103 is started.

[0083] In step S103, the device control unit 51 applies a voltage to an extraction electrode (not shown) and the like, and introduces the ions S from the sample into the ion trap 20 by the action of the electric field generated by the voltage and the like. After step S103 is completed, step S105 is started. In step S105, the first voltage control unit 511 applies a rectangular wave to the annular electrode 202, and the ions S from the sample are trapped in the ion trap 20. After step S105 is completed, step S107 is started.

[0084] In step S107, the device control unit 51 excludes a portion of the ions trapped by the ion trap 20 based on the m / z. The second voltage control unit 512 applies an FNF signal or a SWIFT signal to the end cap electrode via the second voltage application unit 22, thereby trapping the precursor ions in the ion trap 20 and reducing ions other than the precursor ions. After step S107 is completed, step S109 is started.

[0085] In addition, as long as the precursor ions can be separated with desired accuracy, step S107 may be omitted.

[0086] In step S109, the device control unit 51 controls the gas supply unit 23 to introduce CID gas into the ion trap 20, and the second voltage control unit 512 controls the second voltage application unit 22 to apply a sine wave to the end cap electrode 201, thereby dissociating the precursor ions through CID. After step S109 is completed, step S111 is started. In step S111, the device control unit 51 performs mass separation and detection on the product ions generated by dissociation. After step S111 is completed, step S113 is started.

[0087] In step S113, the data processing unit 52 analyzes the measurement data obtained by the detection. After step S113 is completed, the processing ends.

[0088] The following modifications are also within the scope of the present invention and can be combined with the above-mentioned embodiment. In the following modifications, the same reference numerals are used for the same structures and parts showing functions as those in the above-mentioned embodiment, and the description thereof is omitted as appropriate.

[0089] (Variant 1)

[0090] The ion trap mass spectrometer 1 of the above-mentioned embodiment is configured to include only an ion trap as a mass spectrometer. However, in addition to the ion trap 20, the ion trap mass spectrometer 1 can also include any one or more mass spectrometers, or can also be connected to a gas chromatograph or a liquid chromatograph. The term "ion trap mass spectrometer" in the above-mentioned embodiment refers to a situation that also includes these or a combination thereof. The ion trap mass spectrometer 1 is preferably an ion trap-time-of-flight mass spectrometer. In this case, it is preferred that the ions S derived from the sample generated by dissociation are not discharged by resonant excitation, but are set to be non-selectively discharged regardless of m / z and provided for mass separation by a time-of-flight mass spectrometer. In addition, in the above-mentioned embodiment, it is configured to perform two stages of mass spectrometry, but it is also possible to perform more than two dissociations and perform more than three stages of mass separation.

[0091] (Variant 2)

[0092] In the above-mentioned embodiment, the user may input the amplitude of the sine wave applied by the second voltage control unit 512 via the second voltage applying unit 22 via the input unit 41. The user can input a numerical value using a keyboard or a touch panel or the like in a display element such as a text box displayed on the display screen of the output unit 44 under the control of the output control unit 53. Alternatively, the user may select a numerical value from a drop-down list or the like displayed on the above-mentioned display screen under the control of the output control unit 53. The second voltage control unit 512 functions as a setting unit that sets the amplitude of the voltage of the sine wave based on the input of the user.

[0093] (Variant 3)

[0094] The program for realizing the information processing function of the ion trap mass spectrometer 1 can also be recorded in a computer-readable recording medium, so that the computer system reads and executes the program recorded in the recording medium related to the control of the processing of the above-mentioned device control unit 51 and the processing associated therewith. In addition, the "computer system" mentioned here includes the OS (Operating System) and the hardware of the peripheral devices. In addition, the "computer-readable recording medium" refers to a removable recording medium such as a floppy disk, a magneto-optical disk, an optical disk, a memory card, a hard disk built into the computer system, or a storage device such as an SSD (Solid State Drive). In addition, the "computer-readable recording medium" can also include a medium that dynamically maintains the program in a short time in the form of a communication line in the case of sending the program via a network such as the Internet, a communication line such as a telephone line, and a volatile memory in the computer system of the server or client in this case to maintain the program for a certain period of time. In addition, the above-mentioned program can be used to realize part of the above-mentioned function, and the above-mentioned function can also be realized by combining with a program already recorded in the computer system.

[0095] In addition, when applied to a personal computer (hereinafter referred to as PC) or the like, the program related to the above-mentioned control can be provided via a recording medium such as a DVD-ROM or a data signal such as the Internet. Figure 5 950 is a diagram showing this form. PC950 receives the provision of the program via DVD-ROM953. In addition, PC950 has a connection function with a communication line 951. Computer 952 is a server computer that provides the above-mentioned program, and stores the program in a recording medium such as a hard disk. Communication line 951 is a communication line of the Internet, computer communication, etc., or a dedicated communication line, etc. Computer 952 uses a hard disk to read the program and sends the program to PC950 via communication line 951. That is, the program is transmitted as a data signal through a carrier wave and sent via communication line 951. In this way, the program can be provided as a computer-readable computer program product in various forms such as a recording medium and a carrier wave.

[0096] (plan)

[0097] Those skilled in the art will appreciate that the above-described multiple exemplary embodiments or modifications thereof are specific examples of the following aspects.

[0098] (Item 1) An ion trap mass spectrometer of one embodiment comprises: an ion trap having a first electrode (annular electrode 202) and a second electrode (end cap electrode 201) different from the first electrode; a first voltage control unit that periodically switches a plurality of different DC voltages and applies them to the first electrode; and a second voltage control unit that applies a sinusoidal voltage to the second electrode when ions trapped by the ion trap are dissociated. Thus, when the ion trap is used to dissociate ions, mass spectrometry analysis with good accuracy can be performed.

[0099] (Item 2) In another embodiment of the ion trap mass spectrometer, in the ion trap mass spectrometer described in Item 1, the frequency of the sinusoidal voltage is based on the long-term frequency of the ions. This promotes resonance excitation and enables mass spectrometry with high accuracy.

[0100] (Item 3) In another embodiment of the ion trap mass spectrometer, in the ion trap mass spectrometer described in Item 1 or Item 2, the first voltage control unit applies a rectangular wave voltage to the first electrode to trap the ions inside the ion trap, and the second voltage control unit applies a sinusoidal wave voltage to the second electrode to perform collision induced dissociation of the ions. Thus, mass spectrometry with good accuracy can be performed more reliably.

[0101] (Item 4) In another embodiment of the ion trap mass spectrometer, in the ion trap mass spectrometer described in any one of Items 1 to 3, there is also a setting unit for setting the amplitude of the voltage of the sine wave based on the user's input. Thus, the amplitude of the sine wave can be adjusted in accordance with the analysis conditions, etc., and mass spectrometry with good accuracy can be performed in various situations.

[0102] (Item 5) In another embodiment of the ion trap mass spectrometer, in the ion trap mass spectrometer described in any one of Items 1 to 4, the second voltage control unit applies voltages of different waveforms to the second electrode based on the m / z of the dissociated ions. Thus, the voltage applied to the second electrode can be adjusted in accordance with the dissociated ions, and mass spectrometry with good accuracy can be performed in various situations.

[0103] (Item 6) Another mass spectrometry method uses an ion trap mass spectrometer having an ion trap, wherein the ion trap has a first electrode and a second electrode different from the first electrode, and the mass spectrometry method comprises: periodically switching a plurality of different DC voltages and applying them to the first electrode; and applying a sinusoidal voltage to the second electrode when ions trapped by the ion trap are dissociated. Thus, when the ion trap is used to dissociate ions, mass spectrometry with good accuracy can be performed.

[0104] (Item 7) In a computer-readable medium of one embodiment, a control program is stored for causing a processing device to perform a process of controlling an ion trap mass spectrometer having an ion trap, wherein the ion trap has a first electrode and a second electrode different from the first electrode, wherein the process includes: a first voltage control process (corresponding to Figure 4 The control program of the present invention is as follows: (i) a first electrode is provided with a first electrode and a second electrode is provided with a second voltage control process (corresponding to step S109). The control program of the present invention is as follows: (i) a first electrode is provided with a second voltage control process (corresponding to step S105 in the flowchart of the present invention); a DC voltage of different values ​​is periodically switched and applied to the first electrode; and (ii) a second voltage control process (corresponding to step S109), the control program causes the computer to execute the process. When the ions trapped by the ion trap are dissociated, a sinusoidal voltage is applied to the second electrode. Thus, when the ions are dissociated using the ion trap, a mass spectrometry analysis with good accuracy can be performed.

[0105] The present invention is not limited to the contents of the above-mentioned embodiment, and other aspects that can be conceived within the scope of the technical concept of the present invention are also included in the scope of the present invention.

[0106] [Example]

[0107] Examples are shown below, but the present invention is not limited to the analysis conditions and the like in the following examples.

[0108] (Example 1)

[0109] A sample containing angiotensin II (50 fmol) as a peptide was ionized, the generated ions were trapped in a digital ion trap, and a sine wave was applied to the end cap electrode, thereby providing the trapped ions to the CID. The parameter β was set to 0.3331. Then, a product ion spectrum of the product ions generated in the CID was generated. As an ion trap mass spectrometer, a device with a structure similar to that of the digital ion trap mass spectrometer MALDImini-1 (Shimadzu Corporation) was used. The m / z of the precursor ion was set to 1046.

[0110] Figure 6 is a diagram showing the product ion spectrum obtained in this example. The product ion spectrum shows the m / z of the detected ions on the horizontal axis and the intensity of the detection signal of the ions on the vertical axis. The same is true for the following figures. Figure 6 In the figure, the m / z of the precursor ion is schematically shown by arrow A51. Peak P1 is the peak of the product ion with the highest intensity, and is the peak corresponding to the y sequence ion (y7). The peak intensity of peak P1 is 0.01475, and the RMS (Root Mean Square) of the baseline noise is 0.00006024. The signal-to-noise ratio (S / N ratio) is calculated by dividing the peak intensity by the RMS, which is 244.8.

[0111] (Comparative Example 1)

[0112] The sample containing angiotensin II is ionized, the generated ions are trapped in a digital ion trap, and a rectangular wave is applied to the end cap electrode, thereby providing the trapped ions to the CID. The rectangular wave applied to the end cap electrode is set to be obtained by dividing the rectangular wave applied to the ring electrode by 1 / 6. This is equivalent to parameter β=0.3333. Then, a product ion spectrum of the product ions generated in the CID is generated. Other conditions are the same as in Example 1.

[0113] Figure 7 FIG. 4 is a graph showing the product ion spectrum obtained in this comparative example. Figure 7 In the figure, the m / z of the precursor ion is schematically shown by arrow A52. Peak P2 is the peak of the product ion with the highest intensity, and is the peak corresponding to the y sequence ion (y7). The peak intensity of peak P2 is 0.007777, and the RMS of the baseline noise is 0.00003767. By dividing the peak intensity by the RMS, the S / N ratio is calculated to be 206.5.

[0114] The S / N ratio in Example 1 is higher than that in Comparative Example 1. Furthermore, when the product ion spectrum of Example 1 is compared with the product ion spectrum of Comparative Example 1, the patterns of peaks corresponding to product ions are substantially the same.

[0115] (Example 2)

[0116] A sample containing a peptide consisting of amino acids 18-39 of adrenocorticotropic hormone (ACTH) (hereinafter referred to as ACTH (18-39)) (100 fmol) was ionized, the generated ions were trapped in a digital ion trap, and a sine wave was applied to the end cap electrode, thereby providing the trapped ions to CID. The parameter β was set to 0.3331. Then, a product ion spectrum of the product ions generated in CID was generated. The m / z of the precursor ion was set to 2465. The other conditions were the same as in Example 1.

[0117] Figure 8 FIG. 4 is a graph showing the product ion spectrum obtained in this example. Figure 8 In the figure, the m / z of the precursor ion is schematically shown by arrow A53. Peak P3 is the peak of the product ion with the highest intensity, which is the peak corresponding to the y sequence ion (y20). The peak intensity of peak P3 is 0.03017, and the RMS of the baseline noise is 0.0003855. The S / N ratio is calculated by dividing the peak intensity by the RMS to be 78.3.

[0118] (Comparative Example 2)

[0119] A sample containing ACTH (18-39) is ionized, the generated ions are trapped in a digital ion trap, and a rectangular wave is applied to the end cap electrode, thereby providing the trapped ions to the CID. The rectangular wave applied to the end cap electrode is set to be obtained by dividing the rectangular wave applied to the annular electrode by 1 / 6. This is equivalent to parameter β = 0.3333. Then, a product ion spectrum of the product ions generated in the CID is generated. Other conditions are the same as in Example 1.

[0120] Fig. 9 FIG. 4 is a graph showing the product ion spectrum obtained in this example. Fig. 9 In the figure, the m / z of the precursor ion is schematically shown by arrow A54. Peak P4 is the peak of the product ion with the highest intensity, which is the peak corresponding to the y sequence ion (y20). The peak intensity of peak P4 is 0.001090, and the RMS of the baseline noise is 0.00003973. The S / N ratio is calculated to be 27.4 by dividing the peak intensity by the RMS.

[0121] The S / N ratio in Example 2 is higher than that in Comparative Example 2, and the difference is greater than the difference between Example 1 and Comparative Example 1. In addition, when the product ion spectrum of Example 2 is compared with the product ion spectrum of Comparative Example 2, the pattern of peaks corresponding to product ions is different.

[0122] The disclosures of the following priority applications are incorporated herein by reference.

[0123] Japanese Special Application No. 2019-177979 (applied on September 27, 2019)

[0124] Description of Reference Numerals

[0125] 1 Ion trap mass spectrometer

[0126] 10. Ionization section

[0127] 20 Ion Trap

[0128] 21 First voltage applying unit

[0129] 22 Second voltage applying unit

[0130] 23 Gas supply unit

[0131] 30. Inspection Department

[0132] 40 Information Processing Department

[0133] 41 Input section

[0134] 50 Control Department

[0135] 51 Device control unit

[0136] 100 Measurement Department

[0137] 211 DC Power Supply

[0138] 212 Switching Department

[0139] 201 End cap electrode

[0140] 201a Inlet side end cap electrode

[0141] 201b Outlet side end cap electrode

[0142] 202 Ring Electrode

[0143] 511 1st voltage control unit

[0144] 512 Second voltage control unit

[0145] S Ions from the sample

[0146] Waveforms of the W1, W21, and W22 voltages.

Claims

1. An ion trap mass spectrometer, characterized in that: have: An ion trap comprising a first electrode and a second electrode different from the first electrode; a first voltage control unit that periodically switches a plurality of DC voltages of different values ​​and applies the DC voltages to the first electrode; The second voltage control unit applies a sinusoidal voltage to the second electrode when ions trapped in the ion trap are dissociated.

2. The ion trap mass spectrometer according to claim 1, characterized in that: The frequency of the sinusoidal voltage is based on the frequency of the long-term frequency of the ions.

3. The ion trap mass spectrometer according to claim 1 or 2, characterized in that: The first voltage control unit applies a rectangular wave voltage to the first electrode to trap the ions inside the ion trap. The second voltage control unit performs collision-induced dissociation of the ions by applying a sinusoidal voltage to the second electrode.

4. The ion trap mass spectrometer according to claim 1 or 2, characterized in that: A setting unit is further provided for setting the amplitude of the voltage of the sinusoidal wave based on a user input.

5. The ion trap mass spectrometer according to claim 1 or 2, characterized in that: The second voltage control unit applies voltages of different waveforms to the second electrode based on the m / z of the dissociated ions.

6. A mass spectrometry method using an ion trap mass spectrometer having an ion trap, wherein the ion trap has a first electrode and a second electrode different from the first electrode, characterized in that: have: Periodically switching a plurality of direct current voltages of different values ​​and applying them to the first electrode; When ions trapped in the ion trap are dissociated, a sinusoidal voltage is applied to the second electrode.

7. A computer-readable medium storing a control program for causing a processing device to perform a process of controlling an ion trap mass spectrometer having an ion trap, wherein the ion trap has a first electrode and a second electrode different from the first electrode, wherein: The processing includes: a first voltage control process of periodically switching a plurality of different DC voltage values ​​and applying the DC voltages to the first electrode; The second voltage control process is to apply a sinusoidal voltage to the second electrode when the ions trapped in the ion trap are dissociated. The control program causes a computer to execute the processing.

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