WO2023047546A1 - Mass spectrometry method and mass spectrometer - Google Patents

Mass spectrometry method and mass spectrometer Download PDF

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Publication number
WO2023047546A1
WO2023047546A1 PCT/JP2021/035161 JP2021035161W WO2023047546A1 WO 2023047546 A1 WO2023047546 A1 WO 2023047546A1 JP 2021035161 W JP2021035161 W JP 2021035161W WO 2023047546 A1 WO2023047546 A1 WO 2023047546A1
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Prior art keywords
ionization
sample liquid
unit
nozzle
heating
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PCT/JP2021/035161
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French (fr)
Japanese (ja)
Inventor
圭祐 磯
航 福井
功明 小寺澤
和男 向畑
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株式会社島津製作所
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Priority to PCT/JP2021/035161 priority Critical patent/WO2023047546A1/en
Priority to JP2023549269A priority patent/JPWO2023047546A1/ja
Publication of WO2023047546A1 publication Critical patent/WO2023047546A1/en

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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission

Definitions

  • the present invention relates to a mass spectrometry method, and more particularly to a method for setting ionization parameters in a mass spectrometer.
  • ionization methods are known as methods for ionizing samples in mass spectrometers. Such ionization methods can be broadly divided into methods that perform ionization under a vacuum atmosphere and methods that perform ionization under a substantially atmospheric pressure atmosphere. The latter is generally called atmospheric pressure ionization (API). be done.
  • API atmospheric pressure ionization
  • electrospray ionization ESI
  • atmospheric pressure chemical ionization APCI
  • All of these ionization methods involve spraying a sample liquid (for example, a mixture of a sample to be analyzed and a solvent) from a nozzle into an atmosphere of atmospheric pressure.
  • the sample molecules are ionized by applying an electric current, thereby charging and nebulizing the sample liquid.
  • a corona discharge is generated by applying a high voltage to a needle-like discharge electrode provided near the nozzle.
  • Solvent molecules in the sample liquid sprayed from the nozzle are ionized by the corona discharge, and ion-molecule reactions between the generated solvent ions and the sample molecules ionize the sample molecules.
  • the sample liquid sprayed from the nozzle is heated by providing a heater at the tip of the nozzle or by blowing a high-temperature gas onto the spray flow from the nozzle. It promotes vaporization of the solvent in the sample liquid (see Patent Document 1, for example). However, if the heating temperature at this time is too high, the sample liquid boils, and as a result, the ionization of the sample molecules becomes unstable, which sometimes makes it impossible to obtain stable analysis results.
  • the present invention has been made in view of the above points, and an object of the present invention is to provide a mass spectrometer equipped with an ion source that ionizes a sample by atmospheric pressure ionization, in which boiling of a sample liquid in the ion source is eliminated.
  • an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a heating unit that heats the sample liquid sprayed from the nozzle; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator;
  • a method of setting a heating temperature by the heating unit in a mass spectrometer comprising The output signal from the ion detector or the current flowing through the ionization electrode is monitored in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and the sample liquid having a constant composition is being sprayed from the nozzle. , The heating temperature is set to a value lower than the initial temperature when the variation width of the output signal or the current is equal to or greater than a predetermined threshold.
  • a mass spectrometer which has been made to solve the above problems, an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a heating unit that heats the sample liquid sprayed from the nozzle; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature.
  • a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature; a notification unit that notifies a user to set the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold; It has
  • an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a heating unit that heats the sample liquid sprayed from the nozzle; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature.
  • a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature; a setting unit that sets the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold; may have
  • the mass spectrometry method is an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a sample liquid supply unit that continuously supplies the sample liquid to the nozzle; a heating unit that heats the sample liquid sprayed from the nozzle; a high voltage power supply that applies a voltage to the ionization electrode; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; A method of setting ionization parameters in the ionization unit in a mass spectrometer comprising A state in which the heating temperature of the heating unit is set to a predetermined initial temperature, a predetermined initial voltage is applied from the high voltage power source to the ionization electrode, and a sample liquid having a constant composition is sprayed from the nozzle.
  • the heating temperature is set to a value lower than the initial temperature
  • the absolute value of the voltage applied from the high voltage power source to the ionization electrode may be set to a value smaller than the initial voltage
  • the mass spectrometer is an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a sample liquid supply unit that continuously supplies the sample liquid to the nozzle; a heating unit that heats the sample liquid sprayed from the nozzle; a high voltage power supply that applies a voltage to the ionization electrode; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector; determining whether
  • a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of If the possibility is determined to be high, the user is notified to set the heating temperature to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply a notification unit for notifying the user to set the absolute value of the voltage applied to the ionization electrode from to a value smaller than the initial voltage; may have
  • the mass spectrometer is an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a sample liquid supply unit that continuously supplies the sample liquid to the nozzle; a heating unit that heats the sample liquid sprayed from the nozzle; a high voltage power supply that applies a voltage to the ionization electrode; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power source to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector; determining whether
  • a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of If the possibility is determined to be high, the heating temperature is set to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply to the ionization electrode a setting unit that sets the absolute value of the voltage to be applied to a value smaller than the initial voltage; may have
  • the mass spectrometer provided with the ion source (ionization unit) that ionizes the sample by the atmospheric pressure ionization method prevents the sample liquid from boiling in the ion source. stable analysis results can be obtained.
  • FIG. 1 is a schematic configuration diagram of an LC-MS including a mass spectrometer according to one embodiment of the present invention
  • FIG. FIG. 2 is a schematic configuration diagram around an ionization chamber in the mass spectrometer.
  • 4 is a flowchart showing a first example of a procedure for setting ionization parameters in the embodiment
  • 4 is a flow chart showing a second example of a procedure for setting ionization parameters in the embodiment
  • 9 is a flow chart showing a third example of a procedure for setting ionization parameters in the embodiment
  • 9 is a flowchart showing a fourth example of the procedure for setting ionization parameters in the embodiment
  • FIG. 4 is a schematic diagram showing another configuration example of the mass spectrometer in the same embodiment
  • FIG. 4 is a schematic diagram showing still another configuration example of the mass spectrometer in the same embodiment.
  • FIG. 4 is a schematic diagram showing still another configuration example of the mass spectrometer in the same embodiment.
  • FIG. 1 is a schematic configuration diagram of a liquid chromatograph-mass spectrometer (LC-MS) including a mass spectrometer according to the present embodiment
  • FIG. 2 is a schematic diagram showing the configuration around the ionization chamber of the mass spectrometer. is.
  • the mass spectrometer according to this embodiment performs mass spectrometry on a sample liquid eluted from a column of a liquid chromatograph (hereinafter referred to as LC) 180, and performs mass spectrometry to collect data.
  • LC liquid chromatograph-mass spectrometer
  • a measurement unit 110 a data processing unit 170 that processes data collected by the measurement unit 110 , and a control unit 150 that controls the measurement unit 110 .
  • LC180 corresponds to the sample liquid supply unit in the present invention.
  • the control unit 150 is also connected to an input unit 161, which is a pointing device such as a mouse operated by a user (analyzer) or a keyboard, and a display unit 162 such as a liquid crystal display.
  • the LC 180 includes a first liquid-sending pump 183, a second liquid-sending pump 184, a mixer 185, an injector 186, and a column 187.
  • the first liquid-sending pump 183 is the first mobile phase.
  • the mobile phase A eg, organic solvent
  • the second liquid feeding pump 184 sucks the mobile phase B (eg, water) from the second mobile phase container 182 and delivered at a predetermined flow rate. do.
  • Mobile phase A and mobile phase B are mixed in mixer 185 and delivered to column 187 via injector 186 .
  • Injector 186 injects a sample to be analyzed into the mobile phase using a microsyringe or the like, and the sample is sent to column 187 along with the flow of the mobile phase. Various components in the sample are separated as they pass through the column 187 and elute from the outlet end of the column 187 at different times.
  • the effluent from column 187 is sent to a mass spectrometer as a detector.
  • the measurement unit 110 of the mass spectrometer includes an ionization chamber 111 (corresponding to the ionization unit in the present invention) having a substantially atmospheric pressure atmosphere, an analysis chamber 114 maintained at a high vacuum atmosphere by a high-performance vacuum pump (not shown), and these chambers.
  • a first intermediate vacuum chamber 112 and a second intermediate vacuum chamber 113 are provided between the ionization chamber 111 and the analysis chamber 114 and whose degree of vacuum increases stepwise. That is, the measurement unit 110 in this embodiment has a configuration of a multistage differential pumping system.
  • the ionization chamber 111 and the first intermediate vacuum chamber 112 are communicated through an ion introducing tube 129 having a small diameter.
  • the ionization chamber 111 in this embodiment simultaneously performs electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI).
  • An ESI probe 121 which is a spray nozzle for electrospraying, and a needle-shaped discharge electrode (corona needle) 125 for generating corona discharge in the ionization chamber 111 are arranged.
  • the ESI probe 121 includes a capillary 122 to which the sample liquid is supplied, a metal tube 123 through which the capillary 122 is inserted, and a nebulizing gas tube 124 which is substantially coaxial with the capillary 122 and the metal tube 123.
  • a thin tube made of glass, for example, is used as the capillary 122 , and its rear end is connected to the outlet end of the column 187 provided in the LC 180 .
  • the rear end of the nebulizing gas pipe 124 is connected to a gas source 130 such as a nitrogen gas generator or a gas cylinder.
  • the tip of the capillary 122 protrudes from the tip of the nebulizing gas pipe 124 by a predetermined length.
  • a high-voltage power supply 131 for ESI is connected to the metal thin tube 123 .
  • the discharge electrode 125 described above is arranged in front of the spray flow from the ESI probe 121 in the traveling direction, and the discharge electrode 125 is connected to a high voltage power supply 132 for APCI.
  • the metal capillary 123 of the ESI probe 121 and the discharge electrode 125 may be collectively referred to as "ionization electrode”.
  • the ESI high voltage power supply 131 and the APCI high voltage power supply 132 correspond to the high voltage power supply in the present invention.
  • An entrance end of an iontophoresis tube 129 is also arranged in front of the advancing direction of the spray flow from the ESI probe 121 .
  • a block heater 128 (corresponding to a heating section in the present invention) for heating an ion introduction pipe 129 and a dry gas supply pipe 115, which will be described later, is provided.
  • a plate-shaped counter electrode 126 is provided at the boundary between the ionization chamber 111 and the first intermediate vacuum chamber 112
  • a dry gas ejection port 127 is provided at the center of the counter electrode 126 .
  • the dry gas supplied from the gas source 130 and heated by the block heater 128 in the process of passing through the dry gas supply pipe 115 (heated dry gas) is directed toward the spray flow from the ESI probe 121. is ejected.
  • the measurement section 110 is provided with a temperature control section 191 for controlling the temperature of the block heater 128 .
  • the temperature control unit 191 controls the output of the block heater 128 so that the temperature measured by a temperature sensor (not shown) provided near the block heater 128 becomes a predetermined value.
  • Ion guides 141 and 143 are installed in the first intermediate vacuum chamber 112 and the second intermediate vacuum chamber 113, respectively, for converging ions and transporting them to the subsequent stages. are separated by a skimmer 142 having a small hole at the top. Further, in the analysis chamber 114, a quadrupole mass filter 144 (corresponding to the mass separator in the present invention) that separates ions according to m/z, and ions passing through the quadrupole mass filter 144 are detected. An ion detector 145 is arranged. It should be noted that the configuration of each part can be appropriately changed, such as by replacing the quadrupole mass filter 144 with an orthogonal acceleration time-of-flight mass spectrometer.
  • the control unit 150 includes an analysis control unit 151 and a display control unit 152 as functional blocks, and further includes a setting value storage unit 153 that stores setting values for various analysis conditions.
  • the analysis control unit 151 includes an ESI high-voltage power supply 131, an APCI high-voltage power supply 132, and other power supplies not shown (for example, those that apply voltage to the ion guides 141 and 143 or the quadrupole mass filter 144, etc.),
  • the sample is analyzed by LC-MS by controlling the temperature controller 191 and the first and second liquid feeding pumps 183 and 184 of the LC 180, respectively.
  • the display control unit 152 causes the display unit 162 to display information input and set by the user, the result of mass spectrometry, various notifications, and the like.
  • the data processing unit 170 includes a determination unit 171 as a functional block characteristic of the present invention.
  • control unit 150 and the data processing unit 170 are provided by a general-purpose device including a CPU, a memory, and a large-capacity storage device such as a hard disk drive (HDD) or solid state drive (SSD). It can be realized by using a personal computer as a hardware resource and executing dedicated software pre-installed in the computer on the computer.
  • a general-purpose device including a CPU, a memory, and a large-capacity storage device such as a hard disk drive (HDD) or solid state drive (SSD).
  • HDD hard disk drive
  • SSD solid state drive
  • the metal capillary 123 surrounds the capillary 122 through which the sample liquid flows, the sample liquid passing through the capillary 122 is strongly charged by the high voltage applied to the metal capillary 123, and the nebulizing gas tube, which is the outer tube of the capillary 122, is charged. With the help of the nebulizing gas ejected from 124 , the charged droplets are sprayed from the tip of the ESI probe 121 .
  • the dry gas (heated dry gas) heated by the block heater 128 and ejected from the dry gas ejection port 127 is sprayed onto the spray flow from the ESI probe 121 .
  • the solvent in the charged droplets evaporates rapidly, the droplet size becomes smaller, and gas ions are generated by Coulomb repulsive force.
  • the ions generated at this time are mainly derived from medium to high polarity components in the sample.
  • corona discharge is generated by voltage application from the APCI high-voltage power supply 132.
  • This corona discharge ionizes the solvent molecules in the spray stream to produce reactive ions.
  • the reaction ions react (ion-molecule reaction) with the sample molecules in the spray flow, thereby ionizing the sample molecules.
  • the ions generated at this time are mainly derived from low to medium polarity components in the sample.
  • sample ions are sucked into the first intermediate vacuum chamber 112 via the ion introduction tube 129 due to the pressure difference between the ionization chamber 111 and the first intermediate vacuum chamber 112 .
  • Part of the minute droplets left unevaporated in the ionization chamber 111 is also sucked into the ion introduction tube 129 and heated by the block heater 128 inside the tube to evaporate the solvent and promote ionization.
  • the ions that have reached the first intermediate vacuum chamber 112 are converged by the ion guide 141 and sent to the second intermediate vacuum chamber 113 and analysis chamber 114 in the latter stage.
  • the quadrupole mass filter 144 passes only ions having a specific m/z, or repeatedly scans the m/z of the ions to be passed within a predetermined range. Ions passing through the quadrupole mass filter 144 reach the ion detector 145 . The ion detector 145 extracts a current corresponding to the number of ions that have reached it as an ion detection signal. The ion detection signal is digitized by A/D converter 146 and sent to data processing section 170 .
  • the data processing unit 170 processes the data obtained by digitizing the ion detection signal to create, for example, a mass spectrum, a mass chromatogram, or a total ion chromatogram, or to qualitatively identify an unknown compound or a target compound. quantification of
  • This setting work is performed while continuously supplying a standard sample of constant composition containing known components from the LC 180 to the capillary 122 of the ESI probe 121 .
  • the standard sample preferably contains the solvent used in the main analysis, and a sample liquid consisting only of a solvent that does not contain substantial sample components, such as a mobile phase used in LC180, is used as the standard sample. .
  • the analysis control unit 151 controls the ESI high-voltage power supply 131, the APCI high-voltage power supply 132, and a power supply (not shown) so that the metal capillary tube 123 of the ESI probe 121, the discharge electrode 125 and the ion guides 141 and 143 are applied with the same voltage as in the execution of the main analysis (that is, the voltage with the optimum value obtained in advance). Also, the voltage applied to the rod electrodes constituting the quadrupole mass filter 144 is controlled so that the ions originating from the known component pass through the quadrupole mass filter 144 . Also, in the operation of setting the applied voltage, the gas supplied from the gas source 130 to the nebulizing gas pipe 124 and the dry gas jetting port 127 shall have the same composition as the gas used during the execution of this analysis.
  • the user performs a predetermined operation on the input unit 161 to instruct the analysis control unit 151 to start analyzing the standard sample.
  • the analysis control unit 151 under the control of the analysis control unit 151, the supply of the standard sample from the LC 180 to the ESI probe 121 is started, voltage application to the metal capillary 123 and the discharge electrode 125, nebulization gas from the gas source 130 and The supply of the dry gas and the heating of the dry gas by the block heater 128 are started (step 11).
  • a predetermined initial temperature is applied as the heating temperature by the block heater 128 at this time.
  • the initial temperature for example, a general value as a temperature applied to sample analysis is set in advance by the manufacturer or user of the mass spectrometer and stored in the set value storage unit 153 .
  • the standard sample is ionized in the ionization chamber 111 and the generated ions are sent to the quadrupole mass filter 144 via the ion guides 141 and 143 . Since the composition of the standard sample introduced into the ESI probe 121 is constant regardless of time, the signal (ion detection signal) output from the ion detector 145 at this time should also be substantially constant.
  • the determination unit 171 monitors the ion detection signal from the ion detector 145, and when a predetermined time has passed since the start of analysis of the standard sample, the change in the ion detection signal It is determined whether or not the width is greater than or equal to a predetermined threshold (step 12).
  • the set temperature (that is, the initial temperature) of the block heater 128 at this time is the temperature that is applied to this analysis. , and the value is stored in the set value storage unit 153 (step 14).
  • the determination unit 171 determines that the sample liquid is boiling in the ionization chamber 111, and A signal to that effect is output to the analysis control unit 151 .
  • the analysis control unit 151 lowers the heating temperature of the block heater 128 by a predetermined temperature range (step 13). After that, the process returns to step 12, and the processes of steps 12 and 13 are repeatedly executed until it is determined that the variation width of the ion detection signal is below the threshold value (that is, until step 12 becomes No).
  • the set temperature of the block heater 128 at that time is determined as the temperature to be applied to the main analysis, and the value is stored in the set value storage unit 153 (step 14). That is, in this embodiment, the analysis control section 151 and the set value storage section 153 correspond to the setting section of the present invention.
  • the sample to be analyzed is injected from the injector 186 of the LC 180, and separation of the sample to be analyzed by the column 187 and mass spectrometry (main analysis) by the measurement unit 110 are performed. .
  • the analysis control unit 151 reads the temperature setting value (determined in step 14 above) of the block heater 128 stored in the setting value storage unit 153, and based on the temperature setting value, the block heater 128 is to control. As a result, the sample to be analyzed can be ionized at the optimal heating temperature set by the setting operation.
  • the boiling of the sample liquid in the ionization chamber 111 is suppressed, the ionization state in the ionization chamber 111 is stabilized, and a mass spectrometry result with a high SN ratio (i.e., mass spectrum, mass chromatogram, or total ion chromatogram) is obtained. etc.) can be obtained.
  • a mass spectrometry result with a high SN ratio i.e., mass spectrum, mass chromatogram, or total ion chromatogram
  • FIG. 4 shows operations of the control unit 150 and the data processing unit 170 in such a case.
  • the processing that is, steps 21 and 22
  • steps 21 and 22 the processing until it is determined whether the variation width of the ion detection signal is equal to or greater than the threshold is the same as steps 11 and 12 in the flowchart of FIG. Therefore, the description is omitted here.
  • step 22 of the flowchart of FIG. 4 when the determination unit 171 determines that the variation width of the ion detection signal is equal to or greater than the threshold value (therefore, there is a high possibility that the sample liquid is boiling), the display control unit 152 issues a predetermined notification.
  • the screen is displayed on the display unit 162 (step 23).
  • This notification screen displays a message prompting the user to lower the heating temperature of the block heater 128 . That is, in this example, the display control section 152 and the display section 162 correspond to the notification section in the present invention.
  • the user operates the input unit 161 to instruct the control unit 150 to set the heating temperature of the block heater 128 to a value lower than the initial temperature.
  • the control unit 150 Upon receipt of the instruction, the control unit 150 causes the set value storage unit 153 to store a value lower than the initial temperature by a predetermined temperature width as the set temperature to be applied to the main analysis.
  • the user may input a temperature lower than the initial temperature from the input unit 161, and the control unit 150 may store the temperature in the set value storage unit 153 as the set temperature to be applied to the main analysis.
  • the method for setting ionization parameters for a mass spectrometer according to the present invention can also be applied to a mass spectrometer that does not include the determination unit 171 as described above.
  • the unit 152 causes the display unit 162 to display the waveform. Then, when the user visually observes the waveform for a predetermined time and determines that the variation width of the ion detection signal is equal to or greater than a predetermined threshold (thus, there is a high possibility that the sample liquid is boiling) (i.e.
  • step 12 the input unit 161 is operated to instruct the analysis control unit 151 to set the heating temperature of the block heater 128 to a predetermined value lower than the current value (step 13). After that, steps 12 and 13 are repeated until the user determines that the fluctuation range of the ion detection signal displayed on the display unit 162 is below the threshold, and the fluctuation range of the ion detection signal is below the threshold (thus, When it is determined that the possibility of the sample liquid boiling has decreased, the user operates the input unit 161 to set the heating temperature by the block heater 128 at that time as the temperature to be applied to the main analysis. The controller 150 is instructed to do so (step 14). Control unit 150 that has received the instruction stores the value in setting value storage unit 153 .
  • the ionization parameters other than the temperature of the block heater 128 are optimized in advance.
  • the method is not limited to this, and in addition to the temperature of the block heater 128, the voltage applied to the ionization electrode (that is, the metal capillary 123 of the ESI probe 121 and the discharge electrode 125) can be optimized. good.
  • a method of setting the ionization parameter in such a case will be described below.
  • a high voltage is applied to the ionization electrode when ionizing the sample.
  • Undesirable electrical discharge (abnormal electrical discharge) may occur in the sample, destabilizing the ionization of the sample molecules. Therefore, in the following example, when it is determined that the ionization of the sample molecules is unstable based on the fluctuation range of the ion detection signal, whether the cause is the high heating temperature of the block heater 128, It is determined whether the problem is caused by a large voltage applied to the ionization electrode, and depending on the result, the heating temperature is lowered or the applied voltage is decreased.
  • a large (or small) value of the applied voltage means that the absolute value of the applied voltage is large (or small), and a small value of the applied voltage means that the applied voltage is positive or negative. means to reduce its absolute value without changing it.
  • the user performs a predetermined operation on the input unit 161 to instruct the analysis control unit 151 to start analyzing the standard sample.
  • the analysis of the standard sample is started under the control of the analysis control section 151 (step 31).
  • the analysis control unit 151 controls the first liquid-sending pump 183 and the second liquid-sending pump 184 of the LC 180, and the mobile phase A (organic solvent) is sent from the first mobile phase container 181 at a predetermined flow rate.
  • the mobile phase B aqueous solvent
  • Mobile phase A and mobile phase B are mixed in mixer 185 at a predetermined mixing ratio determined by the flow rates of first liquid-sending pump 183 and second liquid-sending pump 184 and sent to column 187 .
  • the values stored in advance by the user in the setting value storage unit 153 as the flow rate applied to the main analysis are applied. be.
  • voltage is applied from the ESI high voltage power supply 131 to the metal capillary tube 123 of the ESI probe 121, and from the APCI high voltage power supply 132 to the discharge electrode 125.
  • a predetermined initial temperature is applied as the heating temperature by the block heater 128 at this time, and the predetermined initial temperature is applied as the applied voltage from the ESI high voltage power supply 131 and the applied voltage from the APCI high voltage power supply 132.
  • voltage is applied.
  • the initial voltage of the ESI high voltage power supply 131 and the initial voltage of the APCI high voltage power supply 132 may be the same value or different values.
  • the mass spectrometer maker or user sets general values for the temperature and voltage applied to the analysis of the sample in advance and stores them in the set value storage unit 153. .
  • the determination unit 171 monitors the ion detection signal from the ion detector 145, When the time has elapsed, it is determined whether or not the variation width of the ion detection signal is greater than or equal to a predetermined threshold value (step 32).
  • the set temperature (that is, the initial temperature) of the block heater 128 at this time and the ESI high The values of the voltages applied by the voltage power supply 131 and the APCI high voltage power supply 132 (that is, the initial voltages) are determined as values to be applied to this analysis, and these values are stored in the set value storage unit 153 (step 40). .
  • the determination unit 171 determines that the ionization of the sample molecules in the ionization chamber 111 is unstable. First, it is determined whether or not the cause is boiling of the sample liquid. Boiling of the sample liquid occurs when the heating temperature by the block heater 128 is high (for example, when the temperature is equal to or higher than the boiling point of the mobile phase solvent), when the organic solvent ratio of the mobile phase is high (for example, when it is 50% or more), and It has been found that this is more likely to occur when the mobile phase flow rate is low (e.g., 1 mL/min or less).
  • the determination unit 171 refers to various setting values of the LC 180 stored in the setting value storage unit 153, and determines whether the initial temperature is equal to or higher than a predetermined threshold value (step 33).
  • the ratio in the above example, the ratio of the "flow rate of the first liquid-sending pump 183" to the “sum of the flow rate of the first liquid-sending pump 183 and the flow rate of the second liquid-sending pump 184" is greater than or equal to a predetermined threshold (step 34), or whether the flow rate of the mobile phase (in the above example, the sum of the flow rate of the first liquid-sending pump 183 and the flow rate of the second liquid-sending pump 184) is equal to or less than the threshold value (step 35).
  • steps 33 to 35 are not limited to the above, and may be performed in any order.
  • the analysis control unit 151 that has received the signal lowers the heating temperature of the block heater 128 by a predetermined temperature width (step 38). Then, it is determined again whether or not the variation width of the ion detection signal is equal to or greater than the predetermined threshold value (step 39). After that, the processing of steps 38 and 39 is repeatedly executed until it is determined in step 39 that the variation width of the ion detection signal is below the threshold value (that is, until step 39 becomes No).
  • the value of the set temperature of the block heater 128 at that time and the value of the voltage applied by the high voltage power supply 131 for ESI and the high voltage power supply for APCI 132 are The temperatures to be applied to the main analysis are determined, and these values are stored in the set value storage unit 153 (step 40).
  • the determination unit 171 sends a signal to that effect to the analysis control unit 151, and the analysis control unit 151 receiving the signal causes the high voltage power supply 131 for ESI and the high voltage power supply 132 for APCI to The applied voltage is reduced by a predetermined voltage width (step 36).
  • the voltage range may be different or the same between the ESI high voltage power supply 131 and the APCI high voltage power supply 132 . Then, it is determined again whether or not the variation width of the ion detection signal is equal to or greater than the predetermined threshold value (step 37). After that, the processes of steps 36 and 37 are repeatedly executed until it is determined in step 37 that the variation width of the ion detection signal is below the threshold value (that is, until step 37 becomes No).
  • the value of the voltage applied by the ESI high-voltage power supply 131 and the APCI high-voltage power supply 132 and the set temperature value of the block heater 128 at that time are The values to be applied to the analysis are determined, and these values are stored in the set value storage unit 153 (step 40).
  • mass spectrometry main analysis of the analysis target sample injected from the injector 186 of the LC 180 is performed.
  • the analysis control unit 151 controls the first liquid-feeding pump 183 and the second liquid-feeding pump 184 so as to feed the mobile phase A and the mobile phase B at the same flow rates as when the ionization parameters were set.
  • the analysis control unit 151 reads out the set value of the heating temperature and the set value of the applied voltage (determined in step 40 above) stored in the set value storage unit 153, and based on the set values, It controls the heater 128, the high voltage power supply 131 for ESI, and the high voltage power supply 132 for APCI.
  • the sample to be analyzed can be ionized with the optimal heating temperature and applied voltage set by the setting operation.
  • the boiling of the solvent and the occurrence of abnormal discharge in the ionization chamber 111 are suppressed, the ionization state in the ionization chamber 111 is stabilized, and the mass spectrometry result with a high SN ratio (i.e., mass spectrum, mass chromatogram, or total ion chromatogram, etc.) can be obtained.
  • FIG. 6 shows operations of the control unit 150 and the data processing unit 170 in such a case.
  • the processing that is, steps 41 and 42
  • steps 41 and 42 the processing until it is determined whether the variation width of the ion detection signal is equal to or greater than the threshold is the same as steps 31 and 32 in the flowchart of FIG. Therefore, the description is omitted here.
  • step 42 of the flowchart of FIG. 6 if the variation width of the ion detection signal is below the threshold value (that is, if No in step 42), the setting temperature (that is, the initial temperature) of the block heater 128 at this time and the values of the voltages applied by the ESI high voltage power supply 131 and the APCI high voltage power supply 132 (that is, the initial voltage) are determined as values to be applied to this analysis, and these values are stored in the set value storage unit 153. Store (step 47).
  • step 42 determines that the variation width of the ion detection signal is equal to or greater than the threshold (that is, if Yes in step 42)
  • the determination unit 171 first determines that the initial temperature is equal to or greater than the predetermined threshold. Whether (step 43), whether the organic solvent ratio in the mobile phase is a predetermined threshold or more (step 44), and whether the flow rate of the mobile phase is less than or equal to the threshold (step 45) are determined in order, If any one of steps 43 to 45 results in Yes, it is determined that the sample liquid is highly likely to be boiling at that time, and a signal to that effect is sent to the display control section 152 . Note that steps 33 to 35 are not limited to the above, and may be performed in any order.
  • the display control unit 152 that has received the signal causes the display unit 162 to display a predetermined notification screen (step 48).
  • This notification screen displays at least a message prompting the user to lower the set temperature of the block heater 128 .
  • the user operates the input unit 161 to instruct the control unit 150 to set the set temperature of the block heater 128 to a value lower than the initial temperature.
  • the control unit 150 causes the set value storage unit 153 to store a value lower than the initial temperature by a predetermined temperature width as the set temperature to be applied to the main analysis.
  • the user may input a temperature lower than the initial temperature from the input unit 161, and the control unit 150 may store the temperature in the set value storage unit 153 as the set temperature to be applied to the main analysis.
  • the determination unit 171 sends a signal to that effect to the display control unit 152, and the display control unit 152 receiving the signal displays a predetermined notification screen. is displayed on the display unit 162 (step 46).
  • This notification screen displays at least a message prompting the user to lower the voltage applied to the metal tube 123 of the ESI probe 121, the voltage applied to the discharge electrode 125, or both.
  • the user operates the input unit 161 to change the set value of the voltage applied to the metal tube 123 of the ESI probe 121, the set value of the voltage applied to the discharge electrode 125, or both to the initial voltage.
  • the controller 150 is instructed to set a value smaller than .
  • the control unit 150 Upon receipt of the instruction, the control unit 150 stores a value smaller than the initial voltage by a predetermined voltage range in the set value storage unit 153 as a voltage value to be applied to the main analysis.
  • the user may input a voltage value smaller than the initial voltage from the input unit 161, and the control unit 150 may store the voltage value in the set value storage unit 153 as the voltage value to be applied to the main analysis. .
  • steps 32 and 42 correspond to the "first determination” in the present invention
  • steps 33 to 35 and steps 43 to 45 correspond to the "first determination” in the present invention. 2 judgment”.
  • the method of setting ionization parameters as shown in FIG. 5 can also be applied to a mass spectrometer that does not include the determination unit 171 as described above.
  • the input unit 161 is operated.
  • the controller 150 is instructed to display various setting items regarding the LC-MS of this embodiment.
  • the control unit 150 Upon receipt of the instruction, the control unit 150 refers to various setting items stored in the setting value storage unit 153, and based thereon, the heating temperature by the block heater 128, the organic solvent ratio of the mobile phase, and the flow rate of the mobile phase. is displayed on the display unit 162 .
  • the values of the organic solvent ratio and the flow rate of the mobile phase are obtained from, for example, the set value of the flow rate of the first liquid-sending pump 183 and the set value of the flow rate of the second liquid-sending pump stored in the set value storage unit 153. be able to.
  • the user confirms these values displayed on the display unit 162, and determines whether the heating temperature of the block heater 128 is equal to or higher than a predetermined threshold, or whether the organic solvent ratio of the mobile phase is equal to or higher than a predetermined threshold. , when it is determined that the mobile phase flow rate is equal to or less than a predetermined threshold value (that is, when any of steps 33 to 35 is Yes), it is determined that the sample liquid is boiling in the ionization chamber 111, and the block heater The analysis controller 151 is instructed to set the heating temperature of 128 to a predetermined value lower than the current value (step 38).
  • steps 38 to 39 are repeated until the user determines that the fluctuation width of the ion detection signal displayed on the display unit 162 is below the threshold value (that is, until step 39 becomes Yes), and the fluctuation width reaches the threshold value.
  • the user operates the input unit 161 to set the value of the heating temperature of the block heater 128 and the value of the voltage applied to the ionization electrode at that time as values to be applied to the main analysis.
  • the controller 150 is instructed to do so (step 40). Control unit 150 that has received the instruction stores the value in setting value storage unit 153 .
  • step 36 determines that an abnormal discharge has occurred in the ionization chamber 111, and the ESI high voltage power supply 131 and the APCI high voltage power supply 132 is reduced by a predetermined voltage width (step 36). After that, steps 36 and 37 are repeated until it is determined that the variation width of the ion detection signal is below the threshold value (that is, until step 37 becomes No).
  • the control unit sets the value of the heating temperature of the block heater 128 and the value of the voltage applied to the ionization electrode at that time as values to be applied to the main analysis. 150 (step 40). Control unit 150 that has received the instruction stores the value in setting value storage unit 153 .
  • the ionization of sample molecules is unstable based on the output signal (ion detection signal) from the ion detector 145.
  • the current flowing in the ionization electrode provided in the ionization chamber 111 that is, the metal capillary 123 or the discharge electrode 125 of the ESI probe 121 (hereinafter referred to as the ionization It may be determined whether or not the ionization of the sample molecules is unstable based on the electrode current).
  • constituent elements that are the same as or correspond to those shown in FIG. 1 are denoted by reference numerals having the same last two digits, and description thereof will be omitted as appropriate.
  • 7 to 9 show some constituent elements for the sake of simplification, the omitted constituent elements have almost the same configuration as in FIG.
  • the ion source in the mass spectrometer shown in FIG. 7 performs ionization by both ESI and APCI similarly to the one shown in FIG. , are connected to a single high voltage power supply 281 . That is, this high-voltage power supply 281 is connected to both the metal thin tube 223 and the discharge electrode 225 by a feeder line 283 having a branch portion 284 .
  • a counter electrode 226 provided between the ionization chamber 211 and the first intermediate vacuum chamber (not shown in FIG. 7) is grounded. A high voltage can be applied between the counter electrode 226 and between the discharge electrode 225 and the counter electrode 226 .
  • the mass spectrometer includes a control unit 250 that controls each unit, and a data processing unit 270 that processes data obtained by an ion detector (not shown) and data obtained by a current detection unit 282. and have.
  • a detection signal from the current detection unit 282 is converted into digital data by the A/D converter 285 and input to the data processing unit 270 .
  • the control unit 250 includes an analysis control unit 251 and a display control unit 252 as functional blocks, and further includes a setting value storage unit 253 that stores setting values of various analysis conditions.
  • the data processing unit 270 has a determination unit 271 as a functional block.
  • the control unit 250 and the data processing unit 270 in this configuration example are also actually computers equipped with a CPU, a memory, a large-capacity storage device, etc., and by executing dedicated software pre-installed in the computer, the above functional blocks can be controlled. function is achieved.
  • FIG. 8 shows ionization by ESI only, and the ionization chamber 311 is provided with an ESI probe 321 similar to that described above, but is not provided with a discharge electrode for APCI.
  • the metal capillary tube 323 of the ESI probe 321 is connected to a high voltage power supply 381 and the counter electrode 326 is grounded.
  • a high voltage is applied between Furthermore, on the feeder line 383 between the metal capillary 323 and the high voltage power supply 381, there is a current flowing through the metal capillary 323 (that is, a current flowing through an electric circuit including the metal capillary 323, the high voltage power supply 381, and the counter electrode 326). ) is provided.
  • the gas port 392 includes a gas supply pipe 393 and a gas port heater 394 (corresponding to a heating section in the present invention) which is a tubular heater surrounding the gas supply pipe 393 .
  • the distal end of the gas supply pipe 393 is directed to the front space of the spray port of the ESI probe 321, and the proximal end of the gas supply pipe 393 is connected to a gas source (not shown) such as a nitrogen gas generator or a gas cylinder.
  • a gas source not shown
  • Other configurations are the same as those in FIG.
  • ionization is performed only by APCI, and the ionization chamber 411 is provided with a discharge electrode 425 for APCI. does not have
  • the discharge electrode 425 is connected to a high voltage power supply 481 and the counter electrode 426 is grounded, and the high voltage power supply 481 applies a high voltage between the discharge electrode 425 and the counter electrode 426. be done.
  • the high voltage power supply 481 applies a high voltage between the discharge electrode 425 and the counter electrode 426. be done.
  • the feed line 483 between the discharge electrode 425 and the high voltage power supply 481 there is a current flowing through the discharge electrode 425 (i.e., a current flowing through an electrical circuit including the discharge electrode 425, the high voltage power supply 481, and the counter electrode 426). ) is provided. 9, instead of the block heater 128 as shown in FIG.
  • a nozzle heater 495 (corresponding to the heating section in the present invention), which is a heater cylindrically surrounding the space in front of the spray port of the spray nozzle 421, is used. is provided.
  • the sample liquid is sprayed from the injection port of the spray nozzle 421 into the space surrounded by the nozzle heater 495, thereby promoting the evaporation of the solvent in the sample liquid.
  • Other configurations are the same as those in FIG.
  • the method of setting ionization parameters for a mass spectrometer according to the present invention can be applied to a mass spectrometer equipped with current detectors 282, 382, and 482 as shown in FIGS. can also be applied.
  • the display control units 252, 352, and 452 cause the display units 262, 362, and 462 to display waveforms representing changes in the ionization electrode current over time, and the user can control the interior of the ionization chambers 211, 311, and 411 based on the waveforms. determines whether the ionization of sample molecules is unstable.
  • the computer is pre-installed with the program for executing the ionization parameter setting method according to the present invention. It is also possible to
  • a mass spectrometry method includes: an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a heating unit that heats the sample liquid sprayed from the nozzle; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; A method of setting a heating temperature by the heating unit in a mass spectrometer comprising The output signal from the ion detector or the current flowing through the ionization electrode is monitored in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and the sample liquid having a constant composition is being sprayed from the nozzle. , The heating temperature is set to a value lower than the initial temperature when the variation width of the output signal or the current is equal to or greater than a predetermined threshold.
  • a mass spectrometer having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a heating unit that heats the sample liquid sprayed from the nozzle; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature.
  • a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature; a notification unit that notifies a user to set the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold; It has
  • a mass spectrometer having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a heating unit that heats the sample liquid sprayed from the nozzle; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature.
  • a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature; a setting unit that sets the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold; may have
  • a mass spectrometer equipped with an ion source (ionization section) for ionizing a sample by atmospheric pressure ionization. , the boiling of the sample liquid in the ion source can be prevented to obtain stable analysis results.
  • a mass spectrometry method includes: an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a sample liquid supply unit that continuously supplies the sample liquid to the nozzle; a heating unit that heats the sample liquid sprayed from the nozzle; a high voltage power supply that applies a voltage to the ionization electrode; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; A method of setting ionization parameters in the ionization unit in a mass spectrometer comprising A state in which the heating temperature of the heating unit is set to a predetermined initial temperature, a predetermined initial voltage is applied from the high voltage power source to the ionization electrode, and a sample liquid having a constant composition is sprayed from the nozzle.
  • the heating temperature is set to a value lower than the initial temperature
  • the absolute value of the voltage applied from the high voltage power source to the ionization electrode may be set to a value smaller than the initial voltage
  • a mass spectrometer having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a sample liquid supply unit that continuously supplies the sample liquid to the nozzle; a heating unit that heats the sample liquid sprayed from the nozzle; a high voltage power supply that applies a voltage to the ionization electrode; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector;
  • a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of If the possibility is determined to be high, the user is notified to set the heating temperature to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply a notification unit for notifying the user to set the absolute value of the voltage applied to the ionization electrode from to a value smaller than the initial voltage; may have
  • an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization; a sample liquid supply unit that continuously supplies the sample liquid to the nozzle; a heating unit that heats the sample liquid sprayed from the nozzle; a high voltage power supply that applies a voltage to the ionization electrode; a mass separator that separates ions generated in the ionization unit according to m/z; an ion detector that detects the ions separated by the mass separator; the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector;
  • a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of If the possibility is determined to be high, the heating temperature is set to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply to the ionization electrode a setting unit that sets the absolute value of the voltage to be applied to a value smaller than the initial voltage; may have
  • a mass spectrometer equipped with an ion source (ionization unit) for ionizing a sample by atmospheric pressure ionization. , the boiling of the sample liquid and the occurrence of abnormal discharge in the ion source can be prevented, and stable analysis results can be obtained.
  • ion source ionization unit

Abstract

This mass spectrometer is provided with: an ionization part which has a nozzle for spraying a sample liquid and an ionization electrode and which ionizes a compound in the sample liquid by an atmospheric pressure ionization method; a heating part which heats the sample liquid sprayed from the nozzle; a mass separator which separates, by m/z, ions generated in the ionization part; and an ion detector which detects ions separated by the mass separator. The heating temperature of the heating part is set to a predetermined initial temperature, and a sample liquid having a certain composition is sprayed from the nozzle (step 11). In this state, an output signal from the ion detector or a current flowing through the ionization electrode is monitored, and if the fluctuation range is equal to or greater than a predetermined threshold value, the heating temperature is set to a value lower than the initial temperature (steps 12-14). As a result, boiling of the sample liquid in the ionization part is prevented and a stable analysis result can be obtained.

Description

質量分析方法及び質量分析装置Mass spectrometry method and mass spectrometer
　本発明は、質量分析方法に関し、特に質量分析装置におけるイオン化パラメータの設定方法に関する。 The present invention relates to a mass spectrometry method, and more particularly to a method for setting ionization parameters in a mass spectrometer.
　質量分析装置において試料をイオン化する手法として様々なイオン化法が知られている。こうしたイオン化法は、真空雰囲気の下でイオン化を行う手法と、略大気圧雰囲気の下でイオン化を行う手法とに大別でき、後者は一般に、大気圧イオン化法（ＡＰＩ：atmospheric pressure ionization）と総称される。 Various ionization methods are known as methods for ionizing samples in mass spectrometers. Such ionization methods can be broadly divided into methods that perform ionization under a vacuum atmosphere and methods that perform ionization under a substantially atmospheric pressure atmosphere. The latter is generally called atmospheric pressure ionization (API). be done.
　大気圧イオン化法としては、エレクトロスプレーイオン化法（ＥＳＩ：electrospray ionization）、又は大気圧化学イオン化法（ＡＰＣＩ：atmospheric pressure chemical ionization）が広く用いられている。これらのイオン化法は、いずれも試料液体（例えば分析対象試料と溶媒との混合物）をノズルから大気圧雰囲気中に噴霧するものであり、ＥＳＩでは、前記ノズルに設けられた金属細管に高電圧を印加し、これにより前記試料液体を帯電させて噴霧することによって、試料分子をイオン化する。一方、ＡＰＣＩでは、前記ノズルの近傍に設けられた針状の放電電極に高電圧を印加することによってコロナ放電を生成する。そして、前記ノズルから噴霧された試料液体中の溶媒分子を前記コロナ放電によってイオン化し、生成した溶媒イオンと試料分子とのイオン－分子反応によって前記試料分子をイオン化する。 As the atmospheric pressure ionization method, electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) is widely used. All of these ionization methods involve spraying a sample liquid (for example, a mixture of a sample to be analyzed and a solvent) from a nozzle into an atmosphere of atmospheric pressure. The sample molecules are ionized by applying an electric current, thereby charging and nebulizing the sample liquid. On the other hand, in APCI, a corona discharge is generated by applying a high voltage to a needle-like discharge electrode provided near the nozzle. Solvent molecules in the sample liquid sprayed from the nozzle are ionized by the corona discharge, and ion-molecule reactions between the generated solvent ions and the sample molecules ionize the sample molecules.
再表2018/100612号公報Retable 2018/100612
　上記のような大気圧イオン化法では、ノズルの先端部にヒータを設けたり、ノズルからの噴霧流に高温のガスを吹き付けたりすることで、ノズルから噴霧された前記試料液体を加熱し、これにより試料液体中の溶媒の気化を促進している（例えば、特許文献１を参照）。しかしながら、このときの加熱温度が高すぎると、試料液体が沸騰してしまい、その結果、試料分子のイオン化が不安定となって、安定した分析結果が得られなくなる場合があった。 In the atmospheric pressure ionization method as described above, the sample liquid sprayed from the nozzle is heated by providing a heater at the tip of the nozzle or by blowing a high-temperature gas onto the spray flow from the nozzle. It promotes vaporization of the solvent in the sample liquid (see Patent Document 1, for example). However, if the heating temperature at this time is too high, the sample liquid boils, and as a result, the ionization of the sample molecules becomes unstable, which sometimes makes it impossible to obtain stable analysis results.
　本発明は、上記の点に鑑みてなされたものであり、その目的とするところは、大気圧イオン化法による試料のイオン化を行うイオン源を備えた質量分析装置において、イオン源における試料液体の沸騰を防止して安定した分析結果を得られるようにすることにある。 The present invention has been made in view of the above points, and an object of the present invention is to provide a mass spectrometer equipped with an ion source that ionizes a sample by atmospheric pressure ionization, in which boiling of a sample liquid in the ion source is eliminated. To obtain stable analysis results by preventing
　上記課題を解決するために成された本発明に係る質量分析方法は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　を備えた質量分析装置において、前記加熱部による加熱温度を設定する方法であって、
　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記ノズルから一定組成の試料液体を噴霧している状態において、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流を監視し、
　前記出力信号又は前記電流の変動幅が予め定められた閾値以上であった場合に、前記加熱温度を前記初期温度よりも低い値に設定するものである。 The mass spectrometry method according to the present invention, which has been made to solve the above problems,
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a heating unit that heats the sample liquid sprayed from the nozzle;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
A method of setting a heating temperature by the heating unit in a mass spectrometer comprising
The output signal from the ion detector or the current flowing through the ionization electrode is monitored in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and the sample liquid having a constant composition is being sprayed from the nozzle. ,
The heating temperature is set to a value lower than the initial temperature when the variation width of the output signal or the current is equal to or greater than a predetermined threshold.
　上記課題を解決するために成された本発明に係る質量分析装置は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　前記加熱部による加熱温度を予め定められた初期温度とした状態で、試料液体の質量分析を実行すべく前記イオン化部、前記加熱部、前記質量分離器、及び前記イオン検出器を制御する制御部と、
　前記初期温度での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する判定部と、
　前記判定部によって前記変動幅が予め定められた閾値以上であると判定された場合に、前記加熱温度を前記初期温度よりも低い値に設定するようユーザに通知する通知部と、
　を有するものである。 A mass spectrometer according to the present invention, which has been made to solve the above problems,
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a heating unit that heats the sample liquid sprayed from the nozzle;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature. and,
a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature;
a notification unit that notifies a user to set the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold;
It has
　また、上記課題を解決するために成された本発明に係る質量分析装置は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　前記加熱部による加熱温度を予め定められた初期温度とした状態で、試料液体の質量分析を実行すべく前記イオン化部、前記加熱部、前記質量分離器、及び前記イオン検出器を制御する制御部と、
　前記初期温度での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する判定部と、
　前記判定部によって前記変動幅が予め定められた閾値以上であると判定された場合に、前記加熱温度を前記初期温度よりも低い値に設定する設定部と、
　を有するものであってもよい。 Further, the mass spectrometer according to the present invention, which has been made to solve the above problems,
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a heating unit that heats the sample liquid sprayed from the nozzle;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature. and,
a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature;
a setting unit that sets the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold;
may have
　また、本発明に係る質量分析方法は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化電極に電圧を印加する高電圧電源と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　を備えた質量分析装置において、前記イオン化部におけるイオン化パラメータを設定する方法であって、
　前記加熱部による加熱温度を予め定められた初期温度とし、前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加し、且つ前記ノズルから一定組成の試料液体を噴霧している状態において、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流を監視し、
　前記出力信号又は前記電流の変動幅が予め定められた閾値以上であった場合に、
　前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判断し、
　前記可能性が高いと判断した場合には、前記加熱温度を前記初期温度よりも低い値に設定し、
　前記可能性が低いと判断した場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定するものであってもよい。 Further, the mass spectrometry method according to the present invention is
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
a heating unit that heats the sample liquid sprayed from the nozzle;
a high voltage power supply that applies a voltage to the ionization electrode;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
A method of setting ionization parameters in the ionization unit in a mass spectrometer comprising
A state in which the heating temperature of the heating unit is set to a predetermined initial temperature, a predetermined initial voltage is applied from the high voltage power source to the ionization electrode, and a sample liquid having a constant composition is sprayed from the nozzle. , monitoring the output signal from the ion detector or the current flowing through the ionization electrode;
When the variation width of the output signal or the current is equal to or greater than a predetermined threshold,
determining whether the possibility that the sample liquid is boiling is high or low based on at least one of the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid;
If it is determined that the possibility is high, the heating temperature is set to a value lower than the initial temperature,
When it is determined that the possibility is low, the absolute value of the voltage applied from the high voltage power source to the ionization electrode may be set to a value smaller than the initial voltage.
　また、本発明に係る質量分析装置は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化電極に電圧を印加する高電圧電源と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加した状態で、試料液体の質量分析を実行すべく前記イオン化部、前記試料液体供給部、前記加熱部、前記高電圧電源、前記質量分離器、及び前記イオン検出器を制御する制御部と、
　前記初期温度且つ前記初期電圧での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する第１の判定を行い、前記第１の判定において前記変動幅が前記閾値以上であると判定した場合には、更に、前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判定する第２の判定を行う判定部と、
　前記可能性が高いと判断された場合には、前記加熱温度を前記初期温度よりも低い値に設定するようユーザに通知し、前記可能性が低いと判断された場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定するようユーザに通知する通知部と、
　を有するものであってもよい。 Further, the mass spectrometer according to the present invention is
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
a heating unit that heats the sample liquid sprayed from the nozzle;
a high voltage power supply that applies a voltage to the ionization electrode;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector;
determining whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of mass spectrometry at the initial temperature and the initial voltage; Determination 1 is performed, and if it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid are further determined. a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of
If the possibility is determined to be high, the user is notified to set the heating temperature to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply a notification unit for notifying the user to set the absolute value of the voltage applied to the ionization electrode from to a value smaller than the initial voltage;
may have
　また、本発明に係る質量分析装置は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化電極に電圧を印加する高電圧電源と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加した状態で、試料液体の質量分析を実行すべく前記イオン化部、前記試料液体供給部、前記加熱部、前記高電圧電源、前記質量分離器、及び前記イオン検出器を制御する制御部と、
　前記初期温度且つ前記初期電圧での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する第１の判定を行い、前記第１の判定において前記変動幅が前記閾値以上であると判定した場合には、更に、前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判定する第２の判定を行う判定部と、
　前記可能性が高いと判断された場合には、前記加熱温度を前記初期温度よりも低い値に設定し、前記可能性が低いと判断された場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定する設定部と、
　を有するものであってもよい。 Further, the mass spectrometer according to the present invention is
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
a heating unit that heats the sample liquid sprayed from the nozzle;
a high voltage power supply that applies a voltage to the ionization electrode;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power source to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector;
determining whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of mass spectrometry at the initial temperature and the initial voltage; Determination 1 is performed, and if it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid are further determined. a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of
If the possibility is determined to be high, the heating temperature is set to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply to the ionization electrode a setting unit that sets the absolute value of the voltage to be applied to a value smaller than the initial voltage;
may have
　上記本発明に係る質量分析方法又は質量分析装置によれば、大気圧イオン化法による試料のイオン化を行うイオン源（イオン化部）を備えた質量分析装置において、イオン源における試料液体の沸騰を防止して安定した分析結果を得られるようになる。 According to the mass spectrometry method or the mass spectrometer according to the present invention, the mass spectrometer provided with the ion source (ionization unit) that ionizes the sample by the atmospheric pressure ionization method prevents the sample liquid from boiling in the ion source. stable analysis results can be obtained.
本発明の一実施形態に係る質量分析装置を含むＬＣ－ＭＳの概略構成図。1 is a schematic configuration diagram of an LC-MS including a mass spectrometer according to one embodiment of the present invention; FIG. 前記質量分析装置におけるイオン化室周辺の概略構成図。FIG. 2 is a schematic configuration diagram around an ionization chamber in the mass spectrometer. 前記実施形態におけるイオン化パラメータの設定手順の第１の例を示すフローチャート。4 is a flowchart showing a first example of a procedure for setting ionization parameters in the embodiment; 前記実施形態におけるイオン化パラメータの設定手順の第２の例を示すフローチャート。4 is a flow chart showing a second example of a procedure for setting ionization parameters in the embodiment; 前記実施形態におけるイオン化パラメータの設定手順の第３の例を示すフローチャート。9 is a flow chart showing a third example of a procedure for setting ionization parameters in the embodiment; 前記実施形態におけるイオン化パラメータの設定手順の第４の例を示すフローチャート。9 is a flowchart showing a fourth example of the procedure for setting ionization parameters in the embodiment; 同実施形態における質量分析装置の別の構成例を示す模式図。FIG. 4 is a schematic diagram showing another configuration example of the mass spectrometer in the same embodiment; 同実施形態における質量分析装置の更に別の構成例を示す模式図。FIG. 4 is a schematic diagram showing still another configuration example of the mass spectrometer in the same embodiment. 同実施形態における質量分析装置の更にまた別の構成例を示す模式図。FIG. 4 is a schematic diagram showing still another configuration example of the mass spectrometer in the same embodiment.
　以下、本発明の一実施形態に係る質量分析装置及びそのイオン化パラメータ設定方法について、図面を参照しつつ説明を行う。図１は、本実施形態に係る質量分析装置を含む液体クロマトグラフ質量分析装置（ＬＣ－ＭＳ）の概略構成図であり、図２は、前記質量分析装置のイオン化室周辺の構成を示す概略図である。本実施形態に係る質量分析装置は、液体クロマトグラフ（以下、ＬＣとよぶ）１８０のカラムから溶出する試料液体に対して質量分析を行うものであって、質量分析を実行してデータを収集する測定部１１０と、測定部１１０で収集されたデータを処理するデータ処理部１７０と、測定部１１０を制御する制御部１５０と、を備えている。ＬＣ１８０が、本発明における試料液体供給部に相当する。また、制御部１５０には、ユーザ（分析担当者）が操作するマウスなどのポインティングデバイス又はキーボードである入力部１６１と、液晶ディスプレイ等の表示部１６２とが接続されている。 A mass spectrometer according to an embodiment of the present invention and an ionization parameter setting method thereof will be described below with reference to the drawings. FIG. 1 is a schematic configuration diagram of a liquid chromatograph-mass spectrometer (LC-MS) including a mass spectrometer according to the present embodiment, and FIG. 2 is a schematic diagram showing the configuration around the ionization chamber of the mass spectrometer. is. The mass spectrometer according to this embodiment performs mass spectrometry on a sample liquid eluted from a column of a liquid chromatograph (hereinafter referred to as LC) 180, and performs mass spectrometry to collect data. A measurement unit 110 , a data processing unit 170 that processes data collected by the measurement unit 110 , and a control unit 150 that controls the measurement unit 110 . LC180 corresponds to the sample liquid supply unit in the present invention. The control unit 150 is also connected to an input unit 161, which is a pointing device such as a mouse operated by a user (analyzer) or a keyboard, and a display unit 162 such as a liquid crystal display.
　図１に示すように、ＬＣ１８０は、第１送液ポンプ１８３、第２送液ポンプ１８４、混合器１８５、インジェクタ１８６、及びカラム１８７を備えており、第１送液ポンプ１８３は第１移動相容器１８１から移動相Ａ（例えば有機溶媒）を吸引して所定流量で送出し、第２送液ポンプ１８４は第２移動相容器１８２から移動相Ｂ（例えば水）を吸引して所定流量で送出する。移動相Ａと移動相Ｂとは混合器１８５で混合され、インジェクタ１８６を経てカラム１８７に送出される。インジェクタ１８６では分析対象の試料がマイクロシリンジなどを用いて移動相中に注入され、該試料は、移動相の流れに乗ってカラム１８７に送り込まれる。試料中の各種成分はカラム１８７を通過する際に分離され、時間差がついてカラム１８７の出口端から溶出する。 As shown in FIG. 1, the LC 180 includes a first liquid-sending pump 183, a second liquid-sending pump 184, a mixer 185, an injector 186, and a column 187. The first liquid-sending pump 183 is the first mobile phase. The mobile phase A (eg, organic solvent) is sucked from the container 181 and delivered at a predetermined flow rate, and the second liquid feeding pump 184 sucks the mobile phase B (eg, water) from the second mobile phase container 182 and delivered at a predetermined flow rate. do. Mobile phase A and mobile phase B are mixed in mixer 185 and delivered to column 187 via injector 186 . Injector 186 injects a sample to be analyzed into the mobile phase using a microsyringe or the like, and the sample is sent to column 187 along with the flow of the mobile phase. Various components in the sample are separated as they pass through the column 187 and elute from the outlet end of the column 187 at different times.
　カラム１８７からの溶出液は検出器としての質量分析装置に送られる。質量分析装置の測定部１１０は、略大気圧雰囲気であるイオン化室１１１（本発明におけるイオン化部に相当）と、図示しない高性能の真空ポンプにより高真空雰囲気に維持される分析室１１４と、それらイオン化室１１１と分析室１１４との間にあって真空度が段階的に高くなっている第１中間真空室１１２及び第２中間真空室１１３と、を備えている。すなわち、本実施形態における測定部１１０は、多段差動排気系の構成を有している。イオン化室１１１と第１中間真空室１１２とは細径のイオン導入管１２９を通して連通している。 The effluent from column 187 is sent to a mass spectrometer as a detector. The measurement unit 110 of the mass spectrometer includes an ionization chamber 111 (corresponding to the ionization unit in the present invention) having a substantially atmospheric pressure atmosphere, an analysis chamber 114 maintained at a high vacuum atmosphere by a high-performance vacuum pump (not shown), and these chambers. A first intermediate vacuum chamber 112 and a second intermediate vacuum chamber 113 are provided between the ionization chamber 111 and the analysis chamber 114 and whose degree of vacuum increases stepwise. That is, the measurement unit 110 in this embodiment has a configuration of a multistage differential pumping system. The ionization chamber 111 and the first intermediate vacuum chamber 112 are communicated through an ion introducing tube 129 having a small diameter.
　本実施形態におけるイオン化室１１１は、エレクトロスプレーイオン化（ＥＳＩ）と、大気圧化学イオン化（ＡＰＣＩ）とを同時に行うものであって、イオン化室１１１の壁面には、試料液体をイオン化室１１１内に静電噴霧するスプレーノズルであるＥＳＩプローブ１２１と、イオン化室１１１内にコロナ放電を発生させる針状の放電電極（コロナニードル）１２５とが配設されている。ＥＳＩプローブ１２１は、図２に示すように、試料液体が供給されるキャピラリ１２２と、該キャピラリ１２２が挿通される金属細管１２３と、キャピラリ１２２及び金属細管１２３と略同軸円筒状であるネブライズガス管１２４と、を含んでいる。なお、キャピラリ１２２としては、例えばガラス製の細管が用いられ、その後端は、ＬＣ１８０に設けられたカラム１８７の出口端に接続されている。また、ネブライズガス管１２４の後端は、窒素ガス発生装置又はガスボンベなどのガス源１３０に接続されている。キャピラリ１２２の先端はネブライズガス管１２４の先端より所定長さだけ突出している。金属細管１２３にはＥＳＩ用高電圧電源１３１が接続されている。 The ionization chamber 111 in this embodiment simultaneously performs electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). An ESI probe 121, which is a spray nozzle for electrospraying, and a needle-shaped discharge electrode (corona needle) 125 for generating corona discharge in the ionization chamber 111 are arranged. As shown in FIG. 2, the ESI probe 121 includes a capillary 122 to which the sample liquid is supplied, a metal tube 123 through which the capillary 122 is inserted, and a nebulizing gas tube 124 which is substantially coaxial with the capillary 122 and the metal tube 123. and includes A thin tube made of glass, for example, is used as the capillary 122 , and its rear end is connected to the outlet end of the column 187 provided in the LC 180 . Also, the rear end of the nebulizing gas pipe 124 is connected to a gas source 130 such as a nitrogen gas generator or a gas cylinder. The tip of the capillary 122 protrudes from the tip of the nebulizing gas pipe 124 by a predetermined length. A high-voltage power supply 131 for ESI is connected to the metal thin tube 123 .
　ＥＳＩプローブ１２１からの噴霧流の進行方向前方には、上述の放電電極１２５が配置され、放電電極１２５にはＡＰＣＩ用高電圧電源１３２が接続されている。以下、ＥＳＩプローブ１２１の金属細管１２３、及び放電電極１２５を、「イオン化電極」と総称することがある。なお、本実施形態においては、ＥＳＩ用高電圧電源１３１及びＡＰＣＩ用高電圧電源１３２が本発明における高電圧電源に相当する。 The discharge electrode 125 described above is arranged in front of the spray flow from the ESI probe 121 in the traveling direction, and the discharge electrode 125 is connected to a high voltage power supply 132 for APCI. Hereinafter, the metal capillary 123 of the ESI probe 121 and the discharge electrode 125 may be collectively referred to as "ionization electrode". In this embodiment, the ESI high voltage power supply 131 and the APCI high voltage power supply 132 correspond to the high voltage power supply in the present invention.
　ＥＳＩプローブ１２１からの噴霧流の進行方向前方には、イオン導入管１２９の入口端も配置されている。イオン化室１１１と第１中間真空室１１２との境界には、イオン導入管１２９及び後述する乾燥ガス供給管１１５を加熱するブロックヒータ１２８（本発明における加熱部に相当）が設けられている。更に、イオン化室１１１と第１中間真空室１１２との境界には、板状の対電極１２６が配設されており、対電極１２６の中央には、乾燥ガス噴出口１２７が設けられている。乾燥ガス噴出口１２７からは、ガス源１３０より供給され、乾燥ガス供給管１１５を通過する過程でブロックヒータ１２８により加熱された乾燥ガス（加熱乾燥ガス）が、ＥＳＩプローブ１２１からの噴霧流に向けて噴出される。更に、測定部１１０には、ブロックヒータ１２８の温度を制御するための温度制御部１９１が設けられている。温度制御部１９１は、ブロックヒータ１２８の近傍に設けられた温度センサ（図示略）で計測される温度が所定の値となるように、ブロックヒータ１２８の出力を制御する。 An entrance end of an iontophoresis tube 129 is also arranged in front of the advancing direction of the spray flow from the ESI probe 121 . At the boundary between the ionization chamber 111 and the first intermediate vacuum chamber 112, a block heater 128 (corresponding to a heating section in the present invention) for heating an ion introduction pipe 129 and a dry gas supply pipe 115, which will be described later, is provided. Further, a plate-shaped counter electrode 126 is provided at the boundary between the ionization chamber 111 and the first intermediate vacuum chamber 112 , and a dry gas ejection port 127 is provided at the center of the counter electrode 126 . From the dry gas outlet 127, the dry gas supplied from the gas source 130 and heated by the block heater 128 in the process of passing through the dry gas supply pipe 115 (heated dry gas) is directed toward the spray flow from the ESI probe 121. is ejected. Furthermore, the measurement section 110 is provided with a temperature control section 191 for controlling the temperature of the block heater 128 . The temperature control unit 191 controls the output of the block heater 128 so that the temperature measured by a temperature sensor (not shown) provided near the block heater 128 becomes a predetermined value.
　第１中間真空室１１２内及び第２中間真空室１１３内にはそれぞれ、イオンを収束させつつ後段へ輸送するイオンガイド１４１、１４３が設置され、第１中間真空室１１２と第２中間真空室１１３との間は、頂部に小孔を有するスキマー１４２で隔てられている。また、分析室１１４内には、イオンをｍ／ｚに応じて分離する四重極マスフィルタ１４４（本発明における質量分離器に相当）と、四重極マスフィルタ１４４を通り抜けたイオンを検出するイオン検出器１４５と、が配置されている。なお、四重極マスフィルタ１４４を直交加速式飛行時間型質量分析器に置き換える等、各部の構成は適宜に変更可能である。 Ion guides 141 and 143 are installed in the first intermediate vacuum chamber 112 and the second intermediate vacuum chamber 113, respectively, for converging ions and transporting them to the subsequent stages. are separated by a skimmer 142 having a small hole at the top. Further, in the analysis chamber 114, a quadrupole mass filter 144 (corresponding to the mass separator in the present invention) that separates ions according to m/z, and ions passing through the quadrupole mass filter 144 are detected. An ion detector 145 is arranged. It should be noted that the configuration of each part can be appropriately changed, such as by replacing the quadrupole mass filter 144 with an orthogonal acceleration time-of-flight mass spectrometer.
　制御部１５０は、分析制御部１５１と、表示制御部１５２とを機能ブロックとして含んでおり、更に、各種分析条件の設定値を記憶する設定値記憶部１５３を備えている。分析制御部１５１は、ＥＳＩ用高電圧電源１３１、ＡＰＣＩ用高電圧電源１３２、及び図示しないその他の電源（例えば、イオンガイド１４１、１４３又は四重極マスフィルタ１４４等に電圧を印加するもの）、温度制御部１９１、並びにＬＣ１８０の第１送液ポンプ１８３及び第２送液ポンプ１８４などをそれぞれ制御することによってＬＣ－ＭＳによる試料の分析を遂行する。表示制御部１５２は、ユーザが入力設定した情報、質量分析の結果、及び各種の通知などを表示部１６２に表示させる。 The control unit 150 includes an analysis control unit 151 and a display control unit 152 as functional blocks, and further includes a setting value storage unit 153 that stores setting values for various analysis conditions. The analysis control unit 151 includes an ESI high-voltage power supply 131, an APCI high-voltage power supply 132, and other power supplies not shown (for example, those that apply voltage to the ion guides 141 and 143 or the quadrupole mass filter 144, etc.), The sample is analyzed by LC-MS by controlling the temperature controller 191 and the first and second liquid feeding pumps 183 and 184 of the LC 180, respectively. The display control unit 152 causes the display unit 162 to display information input and set by the user, the result of mass spectrometry, various notifications, and the like.
　データ処理部１７０は、本発明に特徴的な機能ブロックとして、判定部１７１を備えている。 The data processing unit 170 includes a determination unit 171 as a functional block characteristic of the present invention.
　なお、制御部１５０及びデータ処理部１７０の機能の少なくとも一部は、ＣＰＵと、メモリと、ハードディスクドライブ（ＨＤＤ）又はソリッドステートドライブ（ＳＳＤ）等の大容量記憶装置と、を備えた、汎用のパーソナルコンピュータをハードウエア資源とし、該コンピュータに予めインストールされた専用のソフトウェアを該コンピュータ上で実行することにより実現されるようにすることができる。 Note that at least part of the functions of the control unit 150 and the data processing unit 170 are provided by a general-purpose device including a CPU, a memory, and a large-capacity storage device such as a hard disk drive (HDD) or solid state drive (SSD). It can be realized by using a personal computer as a hardware resource and executing dedicated software pre-installed in the computer on the computer.
　まず、本実施形態に係る質量分析装置における基本的な分析動作について説明する。ＥＳＩプローブ１２１に設けられたキャピラリ１２２の後端には、試料液体として、ＬＣ１８０からの溶出液、すなわち、ＬＣ１８０に設けられたカラム１８７によって分離された試料成分と、溶媒（移動相）との混合液が導入される。また、ＥＳＩ用高電圧電源１３１で発生した高電圧がＥＳＩプローブ１２１の金属細管１２３に印加されると共に、ＡＰＣＩ用高電圧電源１３２で発生した高電圧が放電電極１２５に印加される。金属細管１２３は試料液体が流通するキャピラリ１２２を囲んでいるため、キャピラリ１２２内を通過する試料液体は、金属細管１２３に印加された高電圧によって強く帯電し、キャピラリ１２２の外管であるネブライズガス管１２４から噴出するネブライズガスの助けを受けて、ＥＳＩプローブ１２１の先端から帯電液滴として噴霧される。 First, the basic analysis operation of the mass spectrometer according to this embodiment will be described. At the rear end of the capillary 122 provided in the ESI probe 121, as a sample liquid, an eluate from the LC 180, that is, a mixture of sample components separated by the column 187 provided in the LC 180 and a solvent (mobile phase) Liquid is introduced. A high voltage generated by the ESI high voltage power supply 131 is applied to the metal thin tube 123 of the ESI probe 121 , and a high voltage generated by the APCI high voltage power supply 132 is applied to the discharge electrode 125 . Since the metal capillary 123 surrounds the capillary 122 through which the sample liquid flows, the sample liquid passing through the capillary 122 is strongly charged by the high voltage applied to the metal capillary 123, and the nebulizing gas tube, which is the outer tube of the capillary 122, is charged. With the help of the nebulizing gas ejected from 124 , the charged droplets are sprayed from the tip of the ESI probe 121 .
　このとき、ブロックヒータ１２８によって加熱され、乾燥ガス噴出口１２７から噴出する乾燥ガス（加熱乾燥ガス）が、ＥＳＩプローブ１２１からの噴霧流に吹き付けられる。これにより前記帯電液滴中の溶媒が急速に蒸発して液滴サイズが小さくなり、それに伴って、クーロン反発力によって気体イオンが発生する。なお、このとき発生するイオンは、主に試料中の中～高極性の成分に由来するものである。 At this time, the dry gas (heated dry gas) heated by the block heater 128 and ejected from the dry gas ejection port 127 is sprayed onto the spray flow from the ESI probe 121 . As a result, the solvent in the charged droplets evaporates rapidly, the droplet size becomes smaller, and gas ions are generated by Coulomb repulsive force. The ions generated at this time are mainly derived from medium to high polarity components in the sample.
　更に、放電電極１２５の先端部の周囲では、ＡＰＣＩ用高電圧電源１３２による電圧印加によってコロナ放電が発生する。このコロナ放電によって、前記噴霧流中の溶媒分子がイオン化されて反応イオンが生成される。そして、この反応イオンが前記噴霧流中の試料分子と反応（イオン－分子反応）することによって、該試料分子がイオン化される。このとき発生するイオンは、主に、試料中の低～中極性の成分に由来するものである。 Furthermore, around the tip of the discharge electrode 125, corona discharge is generated by voltage application from the APCI high-voltage power supply 132. This corona discharge ionizes the solvent molecules in the spray stream to produce reactive ions. Then, the reaction ions react (ion-molecule reaction) with the sample molecules in the spray flow, thereby ionizing the sample molecules. The ions generated at this time are mainly derived from low to medium polarity components in the sample.
　こうして発生した試料由来のイオン（試料イオン）は、イオン化室１１１と第１中間真空室１１２との圧力差により、イオン導入管１２９を介して第１中間真空室１１２内に吸い込まれる。また、イオン化室１１１において蒸発しきらずに残った微小な液滴の一部もイオン導入管１２９に吸い込まれ、管内でブロックヒータ１２８に加熱されて溶媒が蒸発し、イオン化が促進される。第１中間真空室１１２に到達したイオンは、イオンガイド１４１により収束されると共に、後段の第２中間真空室１１３及び分析室１１４へと送られる。 The thus generated sample-derived ions (sample ions) are sucked into the first intermediate vacuum chamber 112 via the ion introduction tube 129 due to the pressure difference between the ionization chamber 111 and the first intermediate vacuum chamber 112 . Part of the minute droplets left unevaporated in the ionization chamber 111 is also sucked into the ion introduction tube 129 and heated by the block heater 128 inside the tube to evaporate the solvent and promote ionization. The ions that have reached the first intermediate vacuum chamber 112 are converged by the ion guide 141 and sent to the second intermediate vacuum chamber 113 and analysis chamber 114 in the latter stage.
　分析室１１４では、四重極マスフィルタ１４４が、特定のｍ／ｚを有するイオンのみを通過させるか、あるいは通過させるイオンのｍ／ｚを所定の範囲内で繰り返し走査する。そして、四重極マスフィルタ１４４を通過したイオンがイオン検出器１４５に到達する。イオン検出器１４５では、到達したイオンの数に応じた電流がイオン検出信号として取り出される。前記イオン検出信号はＡ／Ｄ変換器１４６によってデジタル化されて、データ処理部１７０に送られる。データ処理部１７０は、前記イオン検出信号をデジタル化して得られたデータを処理することにより、例えばマススペクトル、マスクロマトグラム、又はトータルイオンクロマトグラムなどを作成したり、未知化合物の定性又は目的化合物の定量などを実施したりする。 In the analysis chamber 114, the quadrupole mass filter 144 passes only ions having a specific m/z, or repeatedly scans the m/z of the ions to be passed within a predetermined range. Ions passing through the quadrupole mass filter 144 reach the ion detector 145 . The ion detector 145 extracts a current corresponding to the number of ions that have reached it as an ion detection signal. The ion detection signal is digitized by A/D converter 146 and sent to data processing section 170 . The data processing unit 170 processes the data obtained by digitizing the ion detection signal to create, for example, a mass spectrum, a mass chromatogram, or a total ion chromatogram, or to qualitatively identify an unknown compound or a target compound. quantification of
　続いて、本実施形態に係る質量分析装置の特徴的な動作について説明する。本実施形態に係る質量分析装置では、本分析（分析対象試料の最終的な分析結果を得るための質量分析）の実行に先立って、イオン化パラメータを最適化するための設定作業が行われる。なお、以下では、イオン化パラメータとしてブロックヒータ１２８の温度設定を行うものとし、他のイオン化パラメータ（例えば、イオン化電極への印加電圧）は、既に最適な値に設定されているものとする。 Next, a characteristic operation of the mass spectrometer according to this embodiment will be described. In the mass spectrometer according to this embodiment, setting work for optimizing the ionization parameters is performed prior to the execution of the main analysis (mass spectrometry for obtaining the final analysis result of the sample to be analyzed). In the following description, it is assumed that the temperature of the block heater 128 is set as an ionization parameter, and that other ionization parameters (for example, the voltage applied to the ionization electrode) have already been set to optimum values.
　この設定作業は、既知成分を含む一定組成の標準試料を、ＬＣ１８０からＥＳＩプローブ１２１のキャピラリ１２２に連続的に供給しつつ行われる。前記標準試料は、前記本分析で使用する溶媒を含むものとすることが望ましく、実質的な試料成分を含まない溶媒のみから成る試料液体、例えばＬＣ１８０で使用される移動相を、前記標準試料として使用する。なお、前記イオン化パラメータの設定作業において、分析制御部１５１は、ＥＳＩ用高電圧電源１３１及びＡＰＣＩ用高電圧電源１３２、並びに図示しない電源を制御することにより、ＥＳＩプローブ１２１の金属細管１２３、放電電極１２５、及びイオンガイド１４１、１４３に前記本分析の実行時と同様の電圧（すなわち予め求められた最適な値の電圧）を印加させる。また、前記既知成分に由来するイオンが四重極マスフィルタ１４４を通過するように、四重極マスフィルタ１４４を構成するロッド電極への印加電圧を制御する。また、前記印加電圧の設定作業において、ガス源１３０からネブライズガス管１２４及び乾燥ガス噴出口１２７へ供給するガスは、本分析の実行時に使用するガスと同様の組成を有するものとする。 This setting work is performed while continuously supplying a standard sample of constant composition containing known components from the LC 180 to the capillary 122 of the ESI probe 121 . The standard sample preferably contains the solvent used in the main analysis, and a sample liquid consisting only of a solvent that does not contain substantial sample components, such as a mobile phase used in LC180, is used as the standard sample. . In setting the ionization parameters, the analysis control unit 151 controls the ESI high-voltage power supply 131, the APCI high-voltage power supply 132, and a power supply (not shown) so that the metal capillary tube 123 of the ESI probe 121, the discharge electrode 125 and the ion guides 141 and 143 are applied with the same voltage as in the execution of the main analysis (that is, the voltage with the optimum value obtained in advance). Also, the voltage applied to the rod electrodes constituting the quadrupole mass filter 144 is controlled so that the ions originating from the known component pass through the quadrupole mass filter 144 . Also, in the operation of setting the applied voltage, the gas supplied from the gas source 130 to the nebulizing gas pipe 124 and the dry gas jetting port 127 shall have the same composition as the gas used during the execution of this analysis.
　前記イオン化パラメータの設定作業（すなわちブロックヒータ１２８の温度設定作業）の実行手順について、図３のフローチャートを参照しつつ説明する。 The execution procedure of the ionization parameter setting work (that is, the temperature setting work of the block heater 128) will be described with reference to the flowchart of FIG.
　まず、ユーザが入力部１６１で所定の操作を行うことにより、分析制御部１５１に標準試料の分析開始を指示する。これにより、分析制御部１５１の制御の下で、ＬＣ１８０からＥＳＩプローブ１２１への前記標準試料の供給が開始されると共に、金属細管１２３及び放電電極１２５への電圧印加、ガス源１３０からのネブライズガス及び乾燥ガスの供給、及びブロックヒータ１２８による前記乾燥ガスの加熱が開始される（ステップ１１）。このときのブロックヒータ１２８による加熱温度としては、予め定められた初期温度が適用される。該初期温度としては、例えば、試料の分析に適用される温度として一般的な値を、予め質量分析装置のメーカ又はユーザが設定して設定値記憶部１５３に記憶させておく。上記により標準試料の分析が開始されると、イオン化室１１１内で標準試料がイオン化され、発生したイオンがイオンガイド１４１、１４３を経て四重極マスフィルタ１４４に送られる。ＥＳＩプローブ１２１に導入される標準試料の組成は時間によらず一定であるため、このときイオン検出器１４５から出力させる信号（イオン検出信号）もほぼ一定となるはずである。しかしながら、イオン化室１１１で試料液体の沸騰が生じた場合には、イオン化室１１１におけるイオン化の状態が不安定となるため、イオン検出信号が大きく変動する。そこで、本実施形態に係る質量分析装置では、判定部１７１が、イオン検出器１４５からのイオン検出信号を監視し、標準試料の分析開始から所定の時間が経過した時点で、イオン検出信号の変動幅が予め定められた閾値以上であるか否かを判定する（ステップ１２）。このとき、イオン検出信号の変動幅が前記閾値を下回っていた場合（すなわちステップ１２でＮｏの場合）には、このときのブロックヒータ１２８の設定温度（すなわち初期温度）を本分析に適用する温度として決定し、その値を設定値記憶部１５３に記憶させる（ステップ１４）。 First, the user performs a predetermined operation on the input unit 161 to instruct the analysis control unit 151 to start analyzing the standard sample. As a result, under the control of the analysis control unit 151, the supply of the standard sample from the LC 180 to the ESI probe 121 is started, voltage application to the metal capillary 123 and the discharge electrode 125, nebulization gas from the gas source 130 and The supply of the dry gas and the heating of the dry gas by the block heater 128 are started (step 11). A predetermined initial temperature is applied as the heating temperature by the block heater 128 at this time. As the initial temperature, for example, a general value as a temperature applied to sample analysis is set in advance by the manufacturer or user of the mass spectrometer and stored in the set value storage unit 153 . When analysis of the standard sample is started as described above, the standard sample is ionized in the ionization chamber 111 and the generated ions are sent to the quadrupole mass filter 144 via the ion guides 141 and 143 . Since the composition of the standard sample introduced into the ESI probe 121 is constant regardless of time, the signal (ion detection signal) output from the ion detector 145 at this time should also be substantially constant. However, when the sample liquid boils in the ionization chamber 111, the ionization state in the ionization chamber 111 becomes unstable, and the ion detection signal fluctuates greatly. Therefore, in the mass spectrometer according to the present embodiment, the determination unit 171 monitors the ion detection signal from the ion detector 145, and when a predetermined time has passed since the start of analysis of the standard sample, the change in the ion detection signal It is determined whether or not the width is greater than or equal to a predetermined threshold (step 12). At this time, if the fluctuation width of the ion detection signal is below the threshold (that is, if No in step 12), the set temperature (that is, the initial temperature) of the block heater 128 at this time is the temperature that is applied to this analysis. , and the value is stored in the set value storage unit 153 (step 14).
　一方、イオン検出信号の変動幅が前記閾値以上であった場合（すなわちステップ１２でＹｅｓの場合）には、判定部１７１が、イオン化室１１１において試料液体の沸騰が生じていると判定し、その旨を示す信号を分析制御部１５１に出力する。前記信号を受けた分析制御部１５１は、ブロックヒータ１２８による加熱温度を予め定められた温度幅だけ低くする（ステップ１３）。その後は、ステップ１２に戻り、イオン検出信号の変動幅が閾値を下回っていると判定されるまで（すなわちステップ１２でＮｏとなるまで）ステップ１２～１３の処理を繰り返し実行する。そして、イオン検出信号の変動幅が閾値を下回ったと判定されたら、そのときのブロックヒータ１２８の設定温度を本分析に適用する温度として決定し、その値を設定値記憶部１５３に記憶させる（ステップ１４）。すなわち、本実施形態においては、分析制御部１５１及び設定値記憶部１５３が本発明における設定部に相当する。 On the other hand, if the variation width of the ion detection signal is equal to or greater than the threshold (that is, if Yes in step 12), the determination unit 171 determines that the sample liquid is boiling in the ionization chamber 111, and A signal to that effect is output to the analysis control unit 151 . Upon receiving the signal, the analysis control unit 151 lowers the heating temperature of the block heater 128 by a predetermined temperature range (step 13). After that, the process returns to step 12, and the processes of steps 12 and 13 are repeatedly executed until it is determined that the variation width of the ion detection signal is below the threshold value (that is, until step 12 becomes No). Then, when it is determined that the variation width of the ion detection signal is below the threshold, the set temperature of the block heater 128 at that time is determined as the temperature to be applied to the main analysis, and the value is stored in the set value storage unit 153 (step 14). That is, in this embodiment, the analysis control section 151 and the set value storage section 153 correspond to the setting section of the present invention.
　以上によりブロックヒータ１２８の温度設定作業が完了した後は、ＬＣ１８０のインジェクタ１８６から分析対象試料を注入して、該分析対象試料のカラム１８７による分離と測定部１１０による質量分析（本分析）を行う。このとき、分析制御部１５１は、設定値記憶部１５３に記憶されているブロックヒータ１２８の温度設定値（上記のステップ１４で決定されたもの）を読み出し、該温度設定値に基づいてブロックヒータ１２８を制御する。これにより、前記設定作業によって設定された最適な加熱温度で分析対象試料のイオン化を行うことができる。その結果、イオン化室１１１における試料液体の沸騰が抑制され、イオン化室１１１内でのイオン化の状態を安定させてＳＮ比の高い質量分析結果（すなわち、マススペクトル、マスクロマトグラム、又はトータルイオンクロマトグラム等）を得ることができる。 After the temperature setting operation of the block heater 128 is completed as described above, the sample to be analyzed is injected from the injector 186 of the LC 180, and separation of the sample to be analyzed by the column 187 and mass spectrometry (main analysis) by the measurement unit 110 are performed. . At this time, the analysis control unit 151 reads the temperature setting value (determined in step 14 above) of the block heater 128 stored in the setting value storage unit 153, and based on the temperature setting value, the block heater 128 is to control. As a result, the sample to be analyzed can be ionized at the optimal heating temperature set by the setting operation. As a result, the boiling of the sample liquid in the ionization chamber 111 is suppressed, the ionization state in the ionization chamber 111 is stabilized, and a mass spectrometry result with a high SN ratio (i.e., mass spectrum, mass chromatogram, or total ion chromatogram) is obtained. etc.) can be obtained.
　なお、上記の例では、判定部１７１において試料液体の沸騰が検知された場合に、自動的にブロックヒータ１２８の設定温度を下げるものとしたが、これに代えて、ユーザに前記設定温度を下げるように通知する構成としてもよい。このような場合における制御部１５０及びデータ処理部１７０の動作を図４に示す。なお、図４のフローチャートにおいて、イオン検出信号の変動幅が閾値以上であるかを判定するまでの処理（すなわちステップ２１～２２）は、上記の図３のフローチャートにおけるステップ１１～１２と同様であるため、ここでは説明を省略する。 In the above example, when the determination unit 171 detects boiling of the sample liquid, the set temperature of the block heater 128 is automatically lowered. It may be configured to notify as follows. FIG. 4 shows operations of the control unit 150 and the data processing unit 170 in such a case. In the flowchart of FIG. 4, the processing (that is, steps 21 and 22) until it is determined whether the variation width of the ion detection signal is equal to or greater than the threshold is the same as steps 11 and 12 in the flowchart of FIG. Therefore, the description is omitted here.
　図４のフローチャートのステップ２２において、イオン検出信号の変動幅が閾値以上である（したがって試料液体が沸騰している可能性が高い）と判定部１７１が判定すると、表示制御部１５２が所定の通知画面を表示部１６２に表示させる（ステップ２３）。この通知画面には、ブロックヒータ１２８による加熱温度を下げるようユーザに促すメッセージを表示するものとする。すなわち、この例においては、表示制御部１５２及び表示部１６２が本発明における通知部に相当する。該通知画面を確認したユーザは、入力部１６１を操作して、ブロックヒータ１２８による加熱温度を、前記初期温度よりも低い値とするよう制御部１５０に指示する。該指示を受けた制御部１５０は、前記初期温度よりも予め定められた温度幅だけ低い値を本分析に適用する設定温度として設定値記憶部１５３に記憶させる。あるいは、ユーザが前記初期温度よりも低い温度を入力部１６１から入力し、制御部１５０が、前記温度を本分析に適用する設定温度として設定値記憶部１５３に記憶させるようにしてもよい。 In step 22 of the flowchart of FIG. 4, when the determination unit 171 determines that the variation width of the ion detection signal is equal to or greater than the threshold value (therefore, there is a high possibility that the sample liquid is boiling), the display control unit 152 issues a predetermined notification. The screen is displayed on the display unit 162 (step 23). This notification screen displays a message prompting the user to lower the heating temperature of the block heater 128 . That is, in this example, the display control section 152 and the display section 162 correspond to the notification section in the present invention. After confirming the notification screen, the user operates the input unit 161 to instruct the control unit 150 to set the heating temperature of the block heater 128 to a value lower than the initial temperature. Upon receipt of the instruction, the control unit 150 causes the set value storage unit 153 to store a value lower than the initial temperature by a predetermined temperature width as the set temperature to be applied to the main analysis. Alternatively, the user may input a temperature lower than the initial temperature from the input unit 161, and the control unit 150 may store the temperature in the set value storage unit 153 as the set temperature to be applied to the main analysis.
　また、本発明に係る質量分析装置のイオン化パラメータ設定方法は、上記のような判定部１７１を備えない質量分析装置にも適用することができる。その場合、図３のステップ１１において標準試料の分析を開始した後は、データ処理部１７０がイオン検出信号の時間変化を示す波形（すなわちマスクロマトグラム又はトータルイオンクロマトグラム）を生成し、表示制御部１５２が該波形を表示部１６２に表示させる。そして、ユーザが所定時間に亘って該波形を視認し、イオン検出信号の変動幅が予め定めた閾値以上である（したがって、試料液体が沸騰している可能性が高い）と判断した場合（すなわちステップ１２でＹｅｓ）には、入力部１６１を操作して、ブロックヒータ１２８による加熱温度を現在の値よりも低い所定の値とするよう分析制御部１５１に指示する（ステップ１３）。その後は、表示部１６２に表示されるイオン検出信号の変動幅が前記閾値を下回ったとユーザが判断するまでステップ１２～１３を繰り返し行い、イオン検出信号の変動幅が前記閾値を下回った（したがって、試料液体が沸騰している可能性が低くなった）と判断した時点で、ユーザが入力部１６１を操作して、そのときのブロックヒータ１２８による加熱温度を、本分析に適用する温度として設定するよう制御部１５０に指示する（ステップ１４）。該指示を受けた制御部１５０は、その値を設定値記憶部１５３に記憶させる。 Further, the method for setting ionization parameters for a mass spectrometer according to the present invention can also be applied to a mass spectrometer that does not include the determination unit 171 as described above. In that case, after starting the analysis of the standard sample in step 11 of FIG. The unit 152 causes the display unit 162 to display the waveform. Then, when the user visually observes the waveform for a predetermined time and determines that the variation width of the ion detection signal is equal to or greater than a predetermined threshold (thus, there is a high possibility that the sample liquid is boiling) (i.e. If Yes at step 12), the input unit 161 is operated to instruct the analysis control unit 151 to set the heating temperature of the block heater 128 to a predetermined value lower than the current value (step 13). After that, steps 12 and 13 are repeated until the user determines that the fluctuation range of the ion detection signal displayed on the display unit 162 is below the threshold, and the fluctuation range of the ion detection signal is below the threshold (thus, When it is determined that the possibility of the sample liquid boiling has decreased, the user operates the input unit 161 to set the heating temperature by the block heater 128 at that time as the temperature to be applied to the main analysis. The controller 150 is instructed to do so (step 14). Control unit 150 that has received the instruction stores the value in setting value storage unit 153 .
　なお、図３又は図４のフローチャートで示したイオン化パラメータの設定方法においては、予め、ブロックヒータ１２８の温度以外のイオン化パラメータが最適化されているものとしたが、本発明に係るイオン化パラメータの設定方法はこれに限定されるものではなく、ブロックヒータ１２８の温度に加えて、イオン化電極（すなわち、ＥＳＩプローブ１２１の金属細管１２３、及び放電電極１２５）への印加電圧の最適化を行うものとしてもよい。このような場合におけるイオン化パラメータの設定方法について以下に説明する。 In the ionization parameter setting method shown in the flowchart of FIG. 3 or FIG. 4, the ionization parameters other than the temperature of the block heater 128 are optimized in advance. The method is not limited to this, and in addition to the temperature of the block heater 128, the voltage applied to the ionization electrode (that is, the metal capillary 123 of the ESI probe 121 and the discharge electrode 125) can be optimized. good. A method of setting the ionization parameter in such a case will be described below.
　図２に示したような大気圧イオン化による試料のイオン化を行うイオン源では、試料をイオン化する際にイオン化電極に高電圧が印加されるが、このときの電圧値が大きすぎると、イオン源にて望ましくない放電（異常放電）が発生して試料分子のイオン化が不安定となることがある。そこで、以下の例では、イオン検出信号の変動幅に基づいて、試料分子のイオン化が不安定になっていると判定した場合に、その原因がブロックヒータ１２８の加熱温度が高いことによるものか、イオン化電極への印加電圧が大きいことによるものかを判断し、その結果に応じて加熱温度を下げるか、あるいは印加電圧を小さくする。なお、本明細書において、印加電圧の値が大きい（又は小さい）とは、印加電圧の絶対値が大きい（又は小さい）ことを意味し、印加電圧の値を小さくするとは、印加電圧の正負を変更することなくその絶対値を小さくすることを意味する。 In an ion source that ionizes a sample by atmospheric pressure ionization as shown in FIG. 2, a high voltage is applied to the ionization electrode when ionizing the sample. Undesirable electrical discharge (abnormal electrical discharge) may occur in the sample, destabilizing the ionization of the sample molecules. Therefore, in the following example, when it is determined that the ionization of the sample molecules is unstable based on the fluctuation range of the ion detection signal, whether the cause is the high heating temperature of the block heater 128, It is determined whether the problem is caused by a large voltage applied to the ionization electrode, and depending on the result, the heating temperature is lowered or the applied voltage is decreased. In this specification, a large (or small) value of the applied voltage means that the absolute value of the applied voltage is large (or small), and a small value of the applied voltage means that the applied voltage is positive or negative. means to reduce its absolute value without changing it.
　具体的な設定作業の手順について、図５のフローチャートを参照しつつ説明する。まず、ユーザが入力部１６１で所定の操作を行うことにより、分析制御部１５１に標準試料の分析開始を指示する。これにより、分析制御部１５１の制御の下で、標準試料の分析が開始される（ステップ３１）。具体的には、分析制御部１５１によってＬＣ１８０の第１送液ポンプ１８３及び第２送液ポンプ１８４が制御され、第１移動相容器１８１から移動相Ａ（有機溶媒）が所定の流量で送出されると共に、第２移動相容器１８２から移動相Ｂ（水系溶媒）が所定の流量で送出される。移動相Ａと移動相Ｂは、混合器１８５において、第１送液ポンプ１８３の流量と第２送液ポンプ１８４の流量によって定まる所定の混合比で混合され、カラム１８７に送出される。このときの第１送液ポンプ１８３の流量及び第２送液ポンプ１８４の流量としては、それぞれ、本分析に適用する流量として予めユーザが設定値記憶部１５３に記憶させておいた値が適用される。また、測定部１１０では、分析制御部１５１の制御の下で、ＥＳＩ用高電圧電源１３１からＥＳＩプローブ１２１の金属細管１２３への電圧印加、ＡＰＣＩ用高電圧電源１３２から放電電極１２５への電圧印加、ガス源１３０からのネブライズガス及び乾燥ガスの供給、及びブロックヒータ１２８による前記乾燥ガスの加熱が開始される。このときのブロックヒータ１２８による加熱温度としては予め定められた初期温度が適用され、ＥＳＩ用高電圧電源１３１からの印加電圧及びＡＰＣＩ用高電圧電源１３２からの印加電圧としては、予め定められた初期電圧が適用される。ここで、ＥＳＩ用高電圧電源１３１の初期電圧と、ＡＰＣＩ用高電圧電源１３２の初期電圧は、同一の値であってもよく、異なる値であってもよい。該初期温度及び初期電圧としては、例えば、試料の分析に適用される温度及び電圧として一般的な値を、予め質量分析装置のメーカ又はユーザが設定して設定値記憶部１５３に記憶させておく。 The specific setting work procedure will be explained with reference to the flowchart in FIG. First, the user performs a predetermined operation on the input unit 161 to instruct the analysis control unit 151 to start analyzing the standard sample. Thereby, the analysis of the standard sample is started under the control of the analysis control section 151 (step 31). Specifically, the analysis control unit 151 controls the first liquid-sending pump 183 and the second liquid-sending pump 184 of the LC 180, and the mobile phase A (organic solvent) is sent from the first mobile phase container 181 at a predetermined flow rate. At the same time, the mobile phase B (aqueous solvent) is delivered from the second mobile phase container 182 at a predetermined flow rate. Mobile phase A and mobile phase B are mixed in mixer 185 at a predetermined mixing ratio determined by the flow rates of first liquid-sending pump 183 and second liquid-sending pump 184 and sent to column 187 . As the flow rate of the first liquid-sending pump 183 and the flow rate of the second liquid-sending pump 184 at this time, the values stored in advance by the user in the setting value storage unit 153 as the flow rate applied to the main analysis are applied. be. In the measurement unit 110, under the control of the analysis control unit 151, voltage is applied from the ESI high voltage power supply 131 to the metal capillary tube 123 of the ESI probe 121, and from the APCI high voltage power supply 132 to the discharge electrode 125. , supply of nebulizing gas and drying gas from gas source 130, and heating of the drying gas by block heater 128 is initiated. A predetermined initial temperature is applied as the heating temperature by the block heater 128 at this time, and the predetermined initial temperature is applied as the applied voltage from the ESI high voltage power supply 131 and the applied voltage from the APCI high voltage power supply 132. voltage is applied. Here, the initial voltage of the ESI high voltage power supply 131 and the initial voltage of the APCI high voltage power supply 132 may be the same value or different values. As the initial temperature and initial voltage, for example, the mass spectrometer maker or user sets general values for the temperature and voltage applied to the analysis of the sample in advance and stores them in the set value storage unit 153. .
　以上により、初期温度及び初期電圧の下での標準試料の質量分析が開始された後は、判定部１７１が、イオン検出器１４５からのイオン検出信号を監視し、前記質量分析の開始から所定の時間が経過した時点で、イオン検出信号の変動幅が予め定められた閾値以上であるか否かを判定する（ステップ３２）。このとき、イオン検出信号の変動幅が前記閾値を下回っていた場合（すなわちステップ３２でＮｏの場合）には、このときのブロックヒータ１２８の設定温度（すなわち初期温度）の値と、ＥＳＩ用高電圧電源１３１及びＡＰＣＩ用高電圧電源１３２による印加電圧（すなわち初期電圧）の値とを、それぞれ本分析に適用する値として決定し、それらの値を設定値記憶部１５３に記憶させる（ステップ４０）。 As described above, after the mass spectrometry of the standard sample is started under the initial temperature and initial voltage, the determination unit 171 monitors the ion detection signal from the ion detector 145, When the time has elapsed, it is determined whether or not the variation width of the ion detection signal is greater than or equal to a predetermined threshold value (step 32). At this time, if the variation width of the ion detection signal is below the threshold value (that is, if No in step 32), the set temperature (that is, the initial temperature) of the block heater 128 at this time and the ESI high The values of the voltages applied by the voltage power supply 131 and the APCI high voltage power supply 132 (that is, the initial voltages) are determined as values to be applied to this analysis, and these values are stored in the set value storage unit 153 (step 40). .
　一方、イオン検出信号の変動幅が前記閾値以上であった場合（すなわちステップ３２でＹｅｓの場合）には、判定部１７１が、イオン化室１１１における試料分子のイオン化が不安定になっていると判定し、まず、その原因が試料液体の沸騰によるものであるか否かを判断する。試料液体の沸騰は、ブロックヒータ１２８による加熱温度が高いとき（例えば、移動相溶媒の沸点以上の温度のとき）、移動相の有機溶媒比率が高いとき（例えば、５０％以上のとき）、及び移動相の流量が低いとき（例えば、1mL/min以下のとき）に発生しやすいことが分かっている。そこで、判定部１７１は、設定値記憶部１５３に記憶されているＬＣ１８０の各種設定値を参照し、前記初期温度が予め定められた閾値以上であるか（ステップ３３）、移動相中の有機溶媒比率（上記の例では「第１送液ポンプ１８３の流量と第２送液ポンプ１８４の流量の和」に対する「第１送液ポンプ１８３の流量」の比率）が予め定められた閾値以上であるか（ステップ３４）、移動相の流量（上記の例では第１送液ポンプ１８３の流量と第２送液ポンプ１８４の流量の和）が閾値以下であるか否か（ステップ３５）を判断し、ステップ３３～３５のいずれか１つでもＹｅｓとなった場合には、その時点で試料液体が沸騰している可能性が高いと判断してその旨を示す信号を分析制御部１５１に送出する。なお、ステップ３３～３５は、上記に限らず、いかなる順番で行ってもよい。該信号を受け取った分析制御部１５１は、ブロックヒータ１２８による加熱温度を予め定められた温度幅だけ低下させる（ステップ３８）。そして、再びイオン検出信号の変動幅が予め定められた閾値以上であるか否かを判定する（ステップ３９）。その後は、ステップ３９において、イオン検出信号の変動幅が閾値を下回っていると判定されるまで（すなわちステップ３９でＮｏとなるまで）ステップ３８～３９の処理を繰り返し実行する。そして、イオン検出信号の変動幅が閾値を下回ったと判定されたら、そのときのブロックヒータ１２８の設定温度の値、並びにＥＳＩ用高電圧電源１３１及びＡＰＣＩ用高電圧電源１３２による印加電圧の値を、本分析に適用する温度として決定し、それらの値を設定値記憶部１５３に記憶させる（ステップ４０）。 On the other hand, when the variation width of the ion detection signal is equal to or greater than the threshold (that is, when Yes in step 32), the determination unit 171 determines that the ionization of the sample molecules in the ionization chamber 111 is unstable. First, it is determined whether or not the cause is boiling of the sample liquid. Boiling of the sample liquid occurs when the heating temperature by the block heater 128 is high (for example, when the temperature is equal to or higher than the boiling point of the mobile phase solvent), when the organic solvent ratio of the mobile phase is high (for example, when it is 50% or more), and It has been found that this is more likely to occur when the mobile phase flow rate is low (e.g., 1 mL/min or less). Therefore, the determination unit 171 refers to various setting values of the LC 180 stored in the setting value storage unit 153, and determines whether the initial temperature is equal to or higher than a predetermined threshold value (step 33). The ratio (in the above example, the ratio of the "flow rate of the first liquid-sending pump 183" to the "sum of the flow rate of the first liquid-sending pump 183 and the flow rate of the second liquid-sending pump 184") is greater than or equal to a predetermined threshold (step 34), or whether the flow rate of the mobile phase (in the above example, the sum of the flow rate of the first liquid-sending pump 183 and the flow rate of the second liquid-sending pump 184) is equal to or less than the threshold value (step 35). If any one of steps 33 to 35 results in Yes, it is judged that there is a high possibility that the sample liquid is boiling at that time, and a signal to that effect is sent to the analysis control section 151. . Note that steps 33 to 35 are not limited to the above, and may be performed in any order. The analysis control unit 151 that has received the signal lowers the heating temperature of the block heater 128 by a predetermined temperature width (step 38). Then, it is determined again whether or not the variation width of the ion detection signal is equal to or greater than the predetermined threshold value (step 39). After that, the processing of steps 38 and 39 is repeatedly executed until it is determined in step 39 that the variation width of the ion detection signal is below the threshold value (that is, until step 39 becomes No). Then, when it is determined that the variation width of the ion detection signal is below the threshold value, the value of the set temperature of the block heater 128 at that time and the value of the voltage applied by the high voltage power supply 131 for ESI and the high voltage power supply for APCI 132 are The temperatures to be applied to the main analysis are determined, and these values are stored in the set value storage unit 153 (step 40).
　一方、ステップ３３～３５の全てがＮｏとなった場合、イオン検出信号の変動幅が大きくなっている（すなわち試料分子のイオン化が不安定になっている）原因は、試料溶液の沸騰ではなく、イオン化室１１１における異常放電の発生によるものであると考えられる。したがって、その場合には、判定部１７１がその旨を示す信号を分析制御部１５１に送出し、該信号を受けた分析制御部１５１が、ＥＳＩ用高電圧電源１３１及びＡＰＣＩ用高電圧電源１３２による印加電圧をそれぞれ予め定められた電圧幅だけ小さくする（ステップ３６）。前記電圧幅は、ＥＳＩ用高電圧電源１３１とＡＰＣＩ用高電圧電源１３２とで異なっていてもよく、同じであってもよい。そして、再びイオン検出信号の変動幅が予め定められた閾値以上であるか否かを判定する（ステップ３７）。その後は、ステップ３７において、イオン検出信号の変動幅が閾値を下回っていると判定されるまで（すなわちステップ３７でＮｏとなるまで）ステップ３６～３７の処理を繰り返し実行する。そして、イオン検出信号の変動幅が閾値を下回ったと判定されたら、そのときのＥＳＩ用高電圧電源１３１及びＡＰＣＩ用高電圧電源１３２による印加電圧の値及びブロックヒータ１２８の設定温度の値を、本分析に適用する値として決定し、それらの値を設定値記憶部１５３に記憶させる（ステップ４０）。 On the other hand, if all of steps 33 to 35 result in No, the cause of the wide fluctuation range of the ion detection signal (that is, the ionization of the sample molecules being unstable) is not the boiling of the sample solution, but the boiling of the sample solution. It is believed that this is due to the occurrence of abnormal discharge in the ionization chamber 111 . Therefore, in that case, the determination unit 171 sends a signal to that effect to the analysis control unit 151, and the analysis control unit 151 receiving the signal causes the high voltage power supply 131 for ESI and the high voltage power supply 132 for APCI to The applied voltage is reduced by a predetermined voltage width (step 36). The voltage range may be different or the same between the ESI high voltage power supply 131 and the APCI high voltage power supply 132 . Then, it is determined again whether or not the variation width of the ion detection signal is equal to or greater than the predetermined threshold value (step 37). After that, the processes of steps 36 and 37 are repeatedly executed until it is determined in step 37 that the variation width of the ion detection signal is below the threshold value (that is, until step 37 becomes No). Then, when it is determined that the variation width of the ion detection signal has fallen below the threshold value, the value of the voltage applied by the ESI high-voltage power supply 131 and the APCI high-voltage power supply 132 and the set temperature value of the block heater 128 at that time are The values to be applied to the analysis are determined, and these values are stored in the set value storage unit 153 (step 40).
　以上によりイオン化パラメータの設定作業が完了した後は、ＬＣ１８０のインジェクタ１８６から分析対象試料を注入した該分析対象試料の質量分析（本分析）を行う。このとき、分析制御部１５１は、前記イオン化パラメータの設定時と同じ流量で移動相Ａ及び移動相Ｂの送液を行うよう第１送液ポンプ１８３及び第２送液ポンプ１８４を制御する。また、分析制御部１５１は、設定値記憶部１５３に記憶されている加熱温度の設定値及び印加電圧の設定値（上記のステップ４０で決定されたもの）を読み出し、該設定値に基づいてブロックヒータ１２８、ＥＳＩ用高電圧電源１３１、及びＡＰＣＩ用高電圧電源１３２を制御する。これにより、前記設定作業によって設定された最適な加熱温度及び印加電圧によって分析対象試料のイオン化を行うことができる。その結果、イオン化室１１１における溶媒の沸騰及び異常放電の発生が抑制され、イオン化室１１１内でのイオン化の状態が安定してＳＮ比の高い質量分析結果（すなわち、マススペクトル、マスクロマトグラム、又はトータルイオンクロマトグラム等）を得ることが可能となる。　 After the ionization parameter setting work is completed as described above, mass spectrometry (main analysis) of the analysis target sample injected from the injector 186 of the LC 180 is performed. At this time, the analysis control unit 151 controls the first liquid-feeding pump 183 and the second liquid-feeding pump 184 so as to feed the mobile phase A and the mobile phase B at the same flow rates as when the ionization parameters were set. Further, the analysis control unit 151 reads out the set value of the heating temperature and the set value of the applied voltage (determined in step 40 above) stored in the set value storage unit 153, and based on the set values, It controls the heater 128, the high voltage power supply 131 for ESI, and the high voltage power supply 132 for APCI. As a result, the sample to be analyzed can be ionized with the optimal heating temperature and applied voltage set by the setting operation. As a result, the boiling of the solvent and the occurrence of abnormal discharge in the ionization chamber 111 are suppressed, the ionization state in the ionization chamber 111 is stabilized, and the mass spectrometry result with a high SN ratio (i.e., mass spectrum, mass chromatogram, or total ion chromatogram, etc.) can be obtained.　
　なお、上記図５の例では、判定部１７１による判定結果に応じて、自動的にブロックヒータ１２８の設定温度を下げたり、イオン化電極への印加電圧を小さくしたりするものとしたが、これに代えて、ユーザに前記設定温度を下げたり、印加電圧を小さくしたりするように通知する構成としてもよい。このような場合における制御部１５０及びデータ処理部１７０の動作を図６に示す。なお、図６のフローチャートにおいて、イオン検出信号の変動幅が閾値以上であるかを判定するまでの処理（すなわちステップ４１～４２）は、上記の図５のフローチャートにおけるステップ３１～３２と同様であるため、ここでは説明を省略する。 In the example shown in FIG. 5, the set temperature of the block heater 128 is automatically lowered or the voltage applied to the ionization electrode is lowered automatically according to the determination result of the determination unit 171. Alternatively, the user may be notified to lower the set temperature or to reduce the applied voltage. FIG. 6 shows operations of the control unit 150 and the data processing unit 170 in such a case. In the flowchart of FIG. 6, the processing (that is, steps 41 and 42) until it is determined whether the variation width of the ion detection signal is equal to or greater than the threshold is the same as steps 31 and 32 in the flowchart of FIG. Therefore, the description is omitted here.
　図６のフローチャートのステップ４２において、イオン検出信号の変動幅が前記閾値を下回っていた場合（すなわちステップ４２でＮｏの場合）には、このときのブロックヒータ１２８の設定温度（すなわち初期温度）の値と、ＥＳＩ用高電圧電源１３１及びＡＰＣＩ用高電圧電源１３２による印加電圧（すなわち初期電圧）の値とを、それぞれ本分析に適用する値として決定し、それらの値を設定値記憶部１５３に記憶させる（ステップ４７）。 In step 42 of the flowchart of FIG. 6, if the variation width of the ion detection signal is below the threshold value (that is, if No in step 42), the setting temperature (that is, the initial temperature) of the block heater 128 at this time and the values of the voltages applied by the ESI high voltage power supply 131 and the APCI high voltage power supply 132 (that is, the initial voltage) are determined as values to be applied to this analysis, and these values are stored in the set value storage unit 153. Store (step 47).
　一方、ステップ４２において、イオン検出信号の変動幅が閾値以上であると判定した場合（すなわちステップ４２でＹｅｓの場合）、判定部１７１は、まず、前記初期温度が予め定められた閾値以上であるか（ステップ４３）、移動相中の有機溶媒比率が予め定められた閾値以上であるか（ステップ４４）、移動相の流量が閾値以下であるか否か（ステップ４５）を順番に判断し、ステップ４３～４５のいずれか１つでもＹｅｓとなった場合には、その時点で試料液体が沸騰している可能性が高いと判断してその旨を示す信号を表示制御部１５２に送出する。なお、ステップ３３～３５は、上記に限らず、いかなる順番で行ってもよい。前記信号を受け取った表示制御部１５２は、所定の通知画面を表示部１６２に表示させる（ステップ４８）。この通知画面には、少なくともブロックヒータ１２８の設定温度を下げるようユーザに促すメッセージを表示するものとする。該通知画面を確認したユーザは、入力部１６１を操作して、ブロックヒータ１２８の設定温度を、前記初期温度よりも小さい値とするよう制御部１５０に指示する。該指示を受けた制御部１５０は、前記初期温度よりも予め定められた温度幅だけ低い値を本分析に適用する設定温度として設定値記憶部１５３に記憶させる。あるいは、ユーザが前記初期温度よりも低い温度を入力部１６１から入力し、制御部１５０が、前記温度を本分析に適用する設定温度として設定値記憶部１５３に記憶させるようにしてもよい。 On the other hand, if it is determined in step 42 that the variation width of the ion detection signal is equal to or greater than the threshold (that is, if Yes in step 42), the determination unit 171 first determines that the initial temperature is equal to or greater than the predetermined threshold. Whether (step 43), whether the organic solvent ratio in the mobile phase is a predetermined threshold or more (step 44), and whether the flow rate of the mobile phase is less than or equal to the threshold (step 45) are determined in order, If any one of steps 43 to 45 results in Yes, it is determined that the sample liquid is highly likely to be boiling at that time, and a signal to that effect is sent to the display control section 152 . Note that steps 33 to 35 are not limited to the above, and may be performed in any order. The display control unit 152 that has received the signal causes the display unit 162 to display a predetermined notification screen (step 48). This notification screen displays at least a message prompting the user to lower the set temperature of the block heater 128 . After confirming the notification screen, the user operates the input unit 161 to instruct the control unit 150 to set the set temperature of the block heater 128 to a value lower than the initial temperature. Upon receipt of the instruction, the control unit 150 causes the set value storage unit 153 to store a value lower than the initial temperature by a predetermined temperature width as the set temperature to be applied to the main analysis. Alternatively, the user may input a temperature lower than the initial temperature from the input unit 161, and the control unit 150 may store the temperature in the set value storage unit 153 as the set temperature to be applied to the main analysis.
　一方、ステップ４３～４５の全てがＮｏとなった場合には、判定部１７１がその旨を示す信号を表示制御部１５２に送出し、該信号を受けた表示制御部１５２が、所定の通知画面を表示部１６２に表示させる（ステップ４６）。この通知画面には、少なくともＥＳＩプローブ１２１の金属細管１２３への印加電圧、放電電極１２５への印加電圧、又はその両方を下げるようユーザに促すメッセージを表示するものとする。該通知画面を確認したユーザは、入力部１６１を操作して、ＥＳＩプローブ１２１の金属細管１２３への印加電圧の設定値、放電電極１２５への印加電圧の設定値、又はその両方を前記初期電圧よりも小さい値とするよう制御部１５０に指示する。該指示を受けた制御部１５０は、前記初期電圧よりも予め定められた電圧幅だけ小さい値を本分析に適用する電圧値として設定値記憶部１５３に記憶させる。あるいは、ユーザが前記初期電圧よりも小さい電圧値を入力部１６１から入力し、制御部１５０が、前記電圧値を本分析に適用する電圧値として設定値記憶部１５３に記憶させるようにしてもよい。 On the other hand, when all of steps 43 to 45 result in No, the determination unit 171 sends a signal to that effect to the display control unit 152, and the display control unit 152 receiving the signal displays a predetermined notification screen. is displayed on the display unit 162 (step 46). This notification screen displays at least a message prompting the user to lower the voltage applied to the metal tube 123 of the ESI probe 121, the voltage applied to the discharge electrode 125, or both. After confirming the notification screen, the user operates the input unit 161 to change the set value of the voltage applied to the metal tube 123 of the ESI probe 121, the set value of the voltage applied to the discharge electrode 125, or both to the initial voltage. The controller 150 is instructed to set a value smaller than . Upon receipt of the instruction, the control unit 150 stores a value smaller than the initial voltage by a predetermined voltage range in the set value storage unit 153 as a voltage value to be applied to the main analysis. Alternatively, the user may input a voltage value smaller than the initial voltage from the input unit 161, and the control unit 150 may store the voltage value in the set value storage unit 153 as the voltage value to be applied to the main analysis. .
　なお、図５及び図６のフローチャートで示した例においては、ステップ３２及びステップ４２が本発明における「第１の判定」に相当し、ステップ３３～３５及びステップ４３～４５が本発明における「第２の判定」に相当する。 5 and 6, steps 32 and 42 correspond to the "first determination" in the present invention, and steps 33 to 35 and steps 43 to 45 correspond to the "first determination" in the present invention. 2 judgment”.
　また、図５に示したようなイオン化パラメータの設定方法は、上記のような判定部１７１を備えない質量分析装置にも適用することができる。その場合、図５のステップ３１において標準試料の分析を開始した後は、データ処理部１７０がイオン検出信号の時間変化を示す波形を生成し、表示制御部１５２が該波形を表示部１６２に表示させる。そして、ユーザが所定時間に亘って該波形を視認し、イオン検出信号の変動幅が予め定めた閾値以上であると判断した場合（すなわちステップ３２でＹｅｓ）には、入力部１６１を操作して本実施形態のＬＣーＭＳに関する各種設定事項を表示するよう制御部１５０に指示する。該指示を受けた制御部１５０では、設定値記憶部１５３に記憶されている各種設定事項を参照し、それに基づいて、ブロックヒータ１２８による加熱温度、移動相の有機溶媒比率、及び移動相の流量の値を表示部１６２に表示させる。なお、有機溶媒比率及び移動相の流量の値は、例えば、設定値記憶部１５３に記憶されている第１送液ポンプ１８３の流量の設定値及び第２送液ポンプの流量の設定値から求めることができる。ユーザは、表示部１６２に表示されたこれらの値を確認し、ブロックヒータ１２８の加熱温度が予め定められた閾値以上であるか、移動相の有機溶媒比率が予め定められた閾値以上であるか、移動相流量が予め定めた閾値以下であると判断した場合（すなわちステップ３３～３５のいずれかがＹｅｓの場合）に、イオン化室１１１において試料液体の沸騰が生じていると判断してブロックヒータ１２８の加熱温度を現在の値よりも低い所定の値とするよう分析制御部１５１に指示する（ステップ３８）。その後は、表示部１６２に表示されるイオン検出信号の変動幅が前記閾値を下回ったとユーザが判断するまで（すなわちステップ３９でＹｅｓとなるまで）ステップ３８～３９を繰り返し行い、前記変動幅が閾値を下回ったと判断した時点で、ユーザが入力部１６１を操作することによって、そのときのブロックヒータ１２８の加熱温度の値及びイオン化電極への印加電圧の値を、それぞれ本分析に適用する値として設定するよう制御部１５０に指示する（ステップ４０）。該指示を受けた制御部１５０は、その値を設定値記憶部１５３に記憶させる。一方、ステップ３３～３５の全てがＮｏであるとユーザが判断した場合には、イオン化室１１１において異常放電が発生していると判断して、ＥＳＩ用高電圧電源１３１及びＡＰＣＩ用高電圧電源１３２による印加電圧をそれぞれ予め定められた電圧幅だけ小さくする（ステップ３６）。その後は、イオン検出信号の変動幅が閾値を下回っていると判定されるまで（すなわちステップ３７でＮｏとなるまで）ステップ３６～３７を繰り返し行い、前記変動幅が閾値を下回ったと判断した時点で、ユーザが入力部１６１で所定の操作を行うことにより、そのときのブロックヒータ１２８の加熱温度の値及びイオン化電極への印加電圧の値を、それぞれ本分析に適用する値として設定するよう制御部１５０に指示する（ステップ４０）。該指示を受けた制御部１５０は、その値を設定値記憶部１５３に記憶させる。 In addition, the method of setting ionization parameters as shown in FIG. 5 can also be applied to a mass spectrometer that does not include the determination unit 171 as described above. In that case, after starting the analysis of the standard sample in step 31 of FIG. Let Then, when the user views the waveform for a predetermined period of time and determines that the variation width of the ion detection signal is equal to or greater than the predetermined threshold value (that is, Yes in step 32), the input unit 161 is operated. The controller 150 is instructed to display various setting items regarding the LC-MS of this embodiment. Upon receipt of the instruction, the control unit 150 refers to various setting items stored in the setting value storage unit 153, and based thereon, the heating temperature by the block heater 128, the organic solvent ratio of the mobile phase, and the flow rate of the mobile phase. is displayed on the display unit 162 . The values of the organic solvent ratio and the flow rate of the mobile phase are obtained from, for example, the set value of the flow rate of the first liquid-sending pump 183 and the set value of the flow rate of the second liquid-sending pump stored in the set value storage unit 153. be able to. The user confirms these values displayed on the display unit 162, and determines whether the heating temperature of the block heater 128 is equal to or higher than a predetermined threshold, or whether the organic solvent ratio of the mobile phase is equal to or higher than a predetermined threshold. , when it is determined that the mobile phase flow rate is equal to or less than a predetermined threshold value (that is, when any of steps 33 to 35 is Yes), it is determined that the sample liquid is boiling in the ionization chamber 111, and the block heater The analysis controller 151 is instructed to set the heating temperature of 128 to a predetermined value lower than the current value (step 38). After that, steps 38 to 39 are repeated until the user determines that the fluctuation width of the ion detection signal displayed on the display unit 162 is below the threshold value (that is, until step 39 becomes Yes), and the fluctuation width reaches the threshold value. , the user operates the input unit 161 to set the value of the heating temperature of the block heater 128 and the value of the voltage applied to the ionization electrode at that time as values to be applied to the main analysis. The controller 150 is instructed to do so (step 40). Control unit 150 that has received the instruction stores the value in setting value storage unit 153 . On the other hand, if the user determines that all of steps 33 to 35 are No, it is determined that an abnormal discharge has occurred in the ionization chamber 111, and the ESI high voltage power supply 131 and the APCI high voltage power supply 132 is reduced by a predetermined voltage width (step 36). After that, steps 36 and 37 are repeated until it is determined that the variation width of the ion detection signal is below the threshold value (that is, until step 37 becomes No). , when the user performs a predetermined operation on the input unit 161, the control unit sets the value of the heating temperature of the block heater 128 and the value of the voltage applied to the ionization electrode at that time as values to be applied to the main analysis. 150 (step 40). Control unit 150 that has received the instruction stores the value in setting value storage unit 153 .
　以上の図３～図６のフローチャートで示した例では、ステップ１２、２２、３２、又は４２において、イオン検出器１４５からの出力信号（イオン検出信号）に基づいて、試料分子のイオン化が不安定になっているか否かを判別するものとしたが、これに代えて、イオン化室１１１に設けられたイオン化電極、すなわちＥＳＩプローブ１２１の金属細管１２３又は放電電極１２５に流れる電流（以下、これをイオン化電極電流とよぶ）に基づいて、試料分子のイオン化が不安定になっているか否かを判定する構成としてもよい。このような場合におけるイオン源の概略構成について図７～図９を参照しつつ説明する。なお、これらの図において、図１に示したものと同一又は対応する構成要素については、下２桁が共通する符号を付し、適宜説明を省略する。また、図７～図９では簡略化のため一部の構成要素を示しているが、省略されている構成要素は、図１とほぼ同一構成を有している。 In the examples shown in the flowcharts of FIGS. 3 to 6 above, in steps 12, 22, 32, or 42, the ionization of sample molecules is unstable based on the output signal (ion detection signal) from the ion detector 145. However, instead of this, the current flowing in the ionization electrode provided in the ionization chamber 111, that is, the metal capillary 123 or the discharge electrode 125 of the ESI probe 121 (hereinafter referred to as the ionization It may be determined whether or not the ionization of the sample molecules is unstable based on the electrode current). A schematic configuration of the ion source in such a case will be described with reference to FIGS. 7 to 9. FIG. In these drawings, constituent elements that are the same as or correspond to those shown in FIG. 1 are denoted by reference numerals having the same last two digits, and description thereof will be omitted as appropriate. 7 to 9 show some constituent elements for the sake of simplification, the omitted constituent elements have almost the same configuration as in FIG.
　図７に示す質量分析装置におけるイオン源は、図１で示したものと同様に、ＥＳＩとＡＰＣＩの両方によるイオン化を行うものであるが、ＥＳＩプローブ２２１の金属細管２２３と、放電電極２２５とが、単一の高電圧電源２８１に接続されている。すなわち、この高電圧電源２８１は、分岐部２８４を有する給電線２８３によって金属細管２２３と放電電極２２５の両方に接続されている。また、イオン化室２１１と第１中間真空室（図７では省略）との間に設けられた対電極２２６は接地されており、これにより、高電圧電源２８１によって、ＥＳＩプローブ２２１の金属細管２２３と対電極２２６の間、及び放電電極２２５と対電極２２６との間に高電圧を印加することができる。更に、給電線２８３の分岐部２８４と高電圧電源２８１との間には、金属細管２２３及び放電電極２２５を流れる電流（すなわち、これらの金属細管２２３、放電電極２２５、高電圧電源２８１、及び対電極２２６を含む電気回路を流れる電流）を検出する電流検出部２８２が設けられている。更に、本構成例に係る質量分析装置は、各部を制御する制御部２５０と、イオン検出器（図示略）で得られたデータ及び電流検出部２８２で得られたデータを処理するデータ処理部２７０と、を備えている。電流検出部２８２による検出信号はＡ／Ｄ変換器２８５でデジタルデータに変換されてデータ処理部２７０に入力される。制御部２５０は、分析制御部２５１及び表示制御部２５２を機能ブロックとして含んでおり、更に各種分析条件の設定値等を記憶する設定値記憶部２５３を備えている。データ処理部２７０は機能ブロックとして判定部２７１を有している。本構成例における制御部２５０及びデータ処理部２７０の実態もＣＰＵ、メモリ、及び大容量記憶装置等を備えたコンピュータであり、該コンピュータに予めインストールされた専用のソフトウェアを実行することにより前記機能ブロックの機能が達成される。 The ion source in the mass spectrometer shown in FIG. 7 performs ionization by both ESI and APCI similarly to the one shown in FIG. , are connected to a single high voltage power supply 281 . That is, this high-voltage power supply 281 is connected to both the metal thin tube 223 and the discharge electrode 225 by a feeder line 283 having a branch portion 284 . A counter electrode 226 provided between the ionization chamber 211 and the first intermediate vacuum chamber (not shown in FIG. 7) is grounded. A high voltage can be applied between the counter electrode 226 and between the discharge electrode 225 and the counter electrode 226 . Furthermore, between the branch portion 284 of the power supply line 283 and the high voltage power source 281, there is a current flowing through the metal thin tube 223 and the discharge electrode 225 (that is, the metal thin tube 223, the discharge electrode 225, the high voltage power source 281, and the pair A current detection unit 282 is provided for detecting a current flowing through an electric circuit including the electrode 226 . Furthermore, the mass spectrometer according to this configuration example includes a control unit 250 that controls each unit, and a data processing unit 270 that processes data obtained by an ion detector (not shown) and data obtained by a current detection unit 282. and have. A detection signal from the current detection unit 282 is converted into digital data by the A/D converter 285 and input to the data processing unit 270 . The control unit 250 includes an analysis control unit 251 and a display control unit 252 as functional blocks, and further includes a setting value storage unit 253 that stores setting values of various analysis conditions. The data processing unit 270 has a determination unit 271 as a functional block. The control unit 250 and the data processing unit 270 in this configuration example are also actually computers equipped with a CPU, a memory, a large-capacity storage device, etc., and by executing dedicated software pre-installed in the computer, the above functional blocks can be controlled. function is achieved.
　図８は、ＥＳＩのみによるイオン化を行うものであり、イオン化室３１１には上記と同様のＥＳＩプローブ３２１が設けられているが、ＡＰＣＩ用の放電電極は設けられていない。同図の構成では、ＥＳＩプローブ３２１の金属細管３２３が高電圧電源３８１に接続されると共に、対電極３２６が接地されており、高電圧電源３８１によって、ＥＳＩプローブ３２１の金属細管３２３と対電極３２６との間に高電圧が印加される。更に、金属細管３２３と高電圧電源３８１との間の給電線３８３上には、金属細管３２３を流れる電流（すなわち、金属細管３２３、高電圧電源３８１、及び対電極３２６を含む電気回路を流れる電流）を検出する電流検出部３８２が設けられている。更に、この例では、図１に示した構成のように、対電極３２６に設けられた乾燥ガス噴出口３２７から噴霧流に向けて加熱乾燥ガスを吹き付ける代わりに、ＥＳＩプローブ３２１の近傍に設けられたガスポート３９２から前記噴霧流に向けて加熱乾燥ガスを吹き付ける構成となっている。ガスポート３９２はガス供給管３９３と、ガス供給管３９３を囲繞する筒状のヒータであるガスポートヒータ３９４（本発明における加熱部に相当）と、を備えている。ガス供給管３９３の先端はＥＳＩプローブ３２１の噴霧口の前方空間に向けられており、ガス供給管３９３の基端は窒素ガス発生装置又はガスボンベ等のガス源（図示略）に接続されている。その他の構成は図７と同様である。 FIG. 8 shows ionization by ESI only, and the ionization chamber 311 is provided with an ESI probe 321 similar to that described above, but is not provided with a discharge electrode for APCI. In the configuration shown in the figure, the metal capillary tube 323 of the ESI probe 321 is connected to a high voltage power supply 381 and the counter electrode 326 is grounded. A high voltage is applied between Furthermore, on the feeder line 383 between the metal capillary 323 and the high voltage power supply 381, there is a current flowing through the metal capillary 323 (that is, a current flowing through an electric circuit including the metal capillary 323, the high voltage power supply 381, and the counter electrode 326). ) is provided. Furthermore, in this example, instead of blowing the heated dry gas toward the spray flow from the dry gas outlet 327 provided in the counter electrode 326 as in the configuration shown in FIG. A heated drying gas is blown toward the spray flow from the gas port 392 . The gas port 392 includes a gas supply pipe 393 and a gas port heater 394 (corresponding to a heating section in the present invention) which is a tubular heater surrounding the gas supply pipe 393 . The distal end of the gas supply pipe 393 is directed to the front space of the spray port of the ESI probe 321, and the proximal end of the gas supply pipe 393 is connected to a gas source (not shown) such as a nitrogen gas generator or a gas cylinder. Other configurations are the same as those in FIG.
　図９は、ＡＰＣＩのみによるイオン化を行うものであり、イオン化室４１１にはＡＰＣＩ用の放電電極４２５が設けられているが、試料液体を噴霧するためのスプレーノズル４２１は、上記のような金属細管を備えていない。同図の構成では、放電電極４２５が高電圧電源４８１に接続されると共に、対電極４２６が接地されており、高電圧電源４８１によって、放電電極４２５と対電極４２６との間に高電圧が印加される。更に、放電電極４２５と高電圧電源４８１との間の給電線４８３上には、放電電極４２５を流れる電流（すなわち、放電電極４２５、高電圧電源４８１、及び対電極４２６を含む電気回路を流れる電流）を検出する電流検出部４８２が設けられている。また、図９の構成では、図１で示したようなブロックヒータ１２８に代えて、スプレーノズル４２１の噴霧口の前方空間を筒状に囲むヒータであるノズルヒータ４９５（本発明における加熱部に相当）が設けられている。試料液体は、スプレーノズル４２１の噴射口からノズルヒータ４９５で囲まれた空間に噴霧され、これによって試料液体中の溶媒の蒸発が促進される。その他の構成は図７と同様である。 In FIG. 9, ionization is performed only by APCI, and the ionization chamber 411 is provided with a discharge electrode 425 for APCI. does not have In the configuration shown in the figure, the discharge electrode 425 is connected to a high voltage power supply 481 and the counter electrode 426 is grounded, and the high voltage power supply 481 applies a high voltage between the discharge electrode 425 and the counter electrode 426. be done. Furthermore, on the feed line 483 between the discharge electrode 425 and the high voltage power supply 481, there is a current flowing through the discharge electrode 425 (i.e., a current flowing through an electrical circuit including the discharge electrode 425, the high voltage power supply 481, and the counter electrode 426). ) is provided. 9, instead of the block heater 128 as shown in FIG. 1, a nozzle heater 495 (corresponding to the heating section in the present invention), which is a heater cylindrically surrounding the space in front of the spray port of the spray nozzle 421, is used. is provided. The sample liquid is sprayed from the injection port of the spray nozzle 421 into the space surrounded by the nozzle heater 495, thereby promoting the evaporation of the solvent in the sample liquid. Other configurations are the same as those in FIG.
　図７～図９のいずれの構成を有する質量分析装置においても、電流検出部２８２、３８２、４８２で検出された電流（以下、「イオン化電極電流」とよぶ）を判定部２７１、３７１、４７１が監視し、該電流の変動幅に基づいて、イオン化室２１１、３１１、４１１内において試料分子のイオン化が不安定となっているか否かを判別する。 In the mass spectrometer having any of the configurations of FIGS. It is determined whether the ionization of the sample molecules is unstable in the ionization chambers 211, 311, and 411 based on the fluctuation range of the current.
　図７～図９の構成におけるイオン化パラメータの設定方法は、図３～図６のフローチャートで示した手順とほぼ同様である。但し、この場合、図３～図６のフローチャート及びその説明における「イオン検出信号」は、「イオン化電極電流」と読み替えることとする。また、ブロックヒータ１２８に代えて、図８のようなガスポートヒータ３９４又は図９のようなノズルヒータ４９５を備えた構成とする場合、図３～図６のフローチャートの説明における「ブロックヒータ１２８」は、「ガスポートヒータ３９４」又は「ノズルヒータ４９５」と読み替えることとする。 The method of setting the ionization parameters in the configurations of FIGS. 7-9 is almost the same as the procedure shown in the flow charts of FIGS. 3-6. However, in this case, the "ion detection signal" in the flowcharts of FIGS. 8 or a nozzle heater 495 as shown in FIG. , "gas port heater 394" or "nozzle heater 495".
　更に、本発明に係る質量分析装置のイオン化パラメータ設定方法は、図７～図９のような電流検出部２８２、３８２、４８２を備え、且つ判定部２７１、３７１、４７１を有しない質量分析装置にも適用することができる。その場合、表示制御部２５２、３５２、４５２が、イオン化電極電流の時間変化を表す波形を表示部２６２、３６２、４６２に表示させ、ユーザが、該波形に基づいてイオン化室２１１、３１１、４１１内において試料分子のイオン化が不安定となっているか否かを判断する。 Furthermore, the method of setting ionization parameters for a mass spectrometer according to the present invention can be applied to a mass spectrometer equipped with current detectors 282, 382, and 482 as shown in FIGS. can also be applied. In that case, the display control units 252, 352, and 452 cause the display units 262, 362, and 462 to display waveforms representing changes in the ionization electrode current over time, and the user can control the interior of the ionization chambers 211, 311, and 411 based on the waveforms. determines whether the ionization of sample molecules is unstable.
　以上、本発明を実施するための形態について具体例を挙げて説明を行ったが、本発明は上記実施形態に限定されるものではなく、本発明の趣旨の範囲で適宜変更が許容される。例えば、上記ではイオン化電極の構成及び加熱部の構成として種々の例を挙げたが、それらの組み合わせは、図１～図２及び図７～図９に例示したものに限らず、いかなる組み合わせとしてもよい。 Although the embodiments for carrying out the present invention have been described above with specific examples, the present invention is not limited to the above-described embodiments, and modifications are permitted as appropriate within the scope of the present invention. For example, various examples of the configuration of the ionization electrode and the configuration of the heating unit have been described above, but the combination thereof is not limited to those illustrated in FIGS. 1 to 2 and FIGS. good.
　また、上記実施形態では、本発明に係るイオン化パラメータの設定方法を実行するためのプログラムがコンピュータに予めインストールされているものとしたが、当該プログラムを、コンピュータ読み取り可能な記録媒体に格納して提供することも可能である。 Further, in the above embodiment, the computer is pre-installed with the program for executing the ionization parameter setting method according to the present invention. It is also possible to
［態様］
　上述した複数の例示的な実施形態は、以下の態様の具体例であることが当業者により理解される。 [Aspect]
It will be appreciated by those skilled in the art that the multiple exemplary embodiments described above are specific examples of the following aspects.
（第１項）一態様に係る質量分析方法は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　を備えた質量分析装置において、前記加熱部による加熱温度を設定する方法であって、
　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記ノズルから一定組成の試料液体を噴霧している状態において、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流を監視し、
　前記出力信号又は前記電流の変動幅が予め定められた閾値以上であった場合に、前記加熱温度を前記初期温度よりも低い値に設定するものである。 (Section 1) A mass spectrometry method according to one aspect includes:
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a heating unit that heats the sample liquid sprayed from the nozzle;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
A method of setting a heating temperature by the heating unit in a mass spectrometer comprising
The output signal from the ion detector or the current flowing through the ionization electrode is monitored in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and the sample liquid having a constant composition is being sprayed from the nozzle. ,
The heating temperature is set to a value lower than the initial temperature when the variation width of the output signal or the current is equal to or greater than a predetermined threshold.
（第２項）一態様に係る質量分析装置は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　前記加熱部による加熱温度を予め定められた初期温度とした状態で、試料液体の質量分析を実行すべく前記イオン化部、前記加熱部、前記質量分離器、及び前記イオン検出器を制御する制御部と、
　前記初期温度での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する判定部と、
　前記判定部によって前記変動幅が予め定められた閾値以上であると判定された場合に、前記加熱温度を前記初期温度よりも低い値に設定するようユーザに通知する通知部と、
　を有するものである。 (Section 2) A mass spectrometer according to one aspect,
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a heating unit that heats the sample liquid sprayed from the nozzle;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature. and,
a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature;
a notification unit that notifies a user to set the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold;
It has
（第３項）一態様に係る質量分析装置は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　前記加熱部による加熱温度を予め定められた初期温度とした状態で、試料液体の質量分析を実行すべく前記イオン化部、前記加熱部、前記質量分離器、及び前記イオン検出器を制御する制御部と、
　前記初期温度での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する判定部と、
　前記判定部によって前記変動幅が予め定められた閾値以上であると判定された場合に、前記加熱温度を前記初期温度よりも低い値に設定する設定部と、
　を有するものであってもよい。 (Section 3) A mass spectrometer according to one aspect,
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a heating unit that heats the sample liquid sprayed from the nozzle;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature. and,
a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature;
a setting unit that sets the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold;
may have
　第１項に記載の質量分析方法、又は第２項若しくは第３項に記載の質量分析装置によれば、大気圧イオン化法による試料のイオン化を行うイオン源（イオン化部）を備えた質量分析装置において、イオン源における試料液体の沸騰を防止して安定した分析結果を得られるようになる。 According to the mass spectrometry method according to item 1 or the mass spectrometer according to item 2 or 3, a mass spectrometer equipped with an ion source (ionization section) for ionizing a sample by atmospheric pressure ionization. , the boiling of the sample liquid in the ion source can be prevented to obtain stable analysis results.
（第４項）一態様に係る質量分析方法は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化電極に電圧を印加する高電圧電源と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　を備えた質量分析装置において、前記イオン化部におけるイオン化パラメータを設定する方法であって、
　前記加熱部による加熱温度を予め定められた初期温度とし、前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加し、且つ前記ノズルから一定組成の試料液体を噴霧している状態において、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流を監視し、
　前記出力信号又は前記電流の変動幅が予め定められた閾値以上であった場合に、
　前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判断し、
　前記可能性が高いと判断した場合には、前記加熱温度を前記初期温度よりも低い値に設定し、
　前記可能性が低いと判断した場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定するものであってもよい。 (Section 4) A mass spectrometry method according to one aspect includes:
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
a heating unit that heats the sample liquid sprayed from the nozzle;
a high voltage power supply that applies a voltage to the ionization electrode;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
A method of setting ionization parameters in the ionization unit in a mass spectrometer comprising
A state in which the heating temperature of the heating unit is set to a predetermined initial temperature, a predetermined initial voltage is applied from the high voltage power source to the ionization electrode, and a sample liquid having a constant composition is sprayed from the nozzle. , monitoring the output signal from the ion detector or the current flowing through the ionization electrode;
When the variation width of the output signal or the current is equal to or greater than a predetermined threshold,
determining whether the possibility that the sample liquid is boiling is high or low based on at least one of the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid;
If it is determined that the possibility is high, the heating temperature is set to a value lower than the initial temperature,
When it is determined that the possibility is low, the absolute value of the voltage applied from the high voltage power source to the ionization electrode may be set to a value smaller than the initial voltage.
（第５項）一態様に係る質量分析装置は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化電極に電圧を印加する高電圧電源と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加した状態で、試料液体の質量分析を実行すべく前記イオン化部、前記試料液体供給部、前記加熱部、前記高電圧電源、前記質量分離器、及び前記イオン検出器を制御する制御部と、
　前記初期温度且つ前記初期電圧での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する第１の判定を行い、前記第１の判定において前記変動幅が前記閾値以上であると判定した場合には、更に、前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判定する第２の判定を行う判定部と、
　前記可能性が高いと判断された場合には、前記加熱温度を前記初期温度よりも低い値に設定するようユーザに通知し、前記可能性が低いと判断された場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定するようユーザに通知する通知部と、
　を有するものであってもよい。 (Section 5) A mass spectrometer according to one aspect,
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
a heating unit that heats the sample liquid sprayed from the nozzle;
a high voltage power supply that applies a voltage to the ionization electrode;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector;
determining whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of mass spectrometry at the initial temperature and the initial voltage; Determination 1 is performed, and if it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid are further determined. a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of
If the possibility is determined to be high, the user is notified to set the heating temperature to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply a notification unit for notifying the user to set the absolute value of the voltage applied to the ionization electrode from to a value smaller than the initial voltage;
may have
（第６項）一態様に係る質量分析装置は、
　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
　前記イオン化電極に電圧を印加する高電圧電源と、
　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加した状態で、試料液体の質量分析を実行すべく前記イオン化部、前記試料液体供給部、前記加熱部、前記高電圧電源、前記質量分離器、及び前記イオン検出器を制御する制御部と、
　前記初期温度且つ前記初期電圧での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する第１の判定を行い、前記第１の判定において前記変動幅が前記閾値以上であると判定した場合には、更に、前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判定する第２の判定を行う判定部と、
　前記可能性が高いと判断された場合には、前記加熱温度を前記初期温度よりも低い値に設定し、前記可能性が低いと判断された場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定する設定部と、
　を有するものであってもよい。 (Section 6) A mass spectrometer according to one aspect,
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
a heating unit that heats the sample liquid sprayed from the nozzle;
a high voltage power supply that applies a voltage to the ionization electrode;
a mass separator that separates ions generated in the ionization unit according to m/z;
an ion detector that detects the ions separated by the mass separator;
the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector;
determining whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of mass spectrometry at the initial temperature and the initial voltage; Determination 1 is performed, and if it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid are further determined. a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of
If the possibility is determined to be high, the heating temperature is set to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply to the ionization electrode a setting unit that sets the absolute value of the voltage to be applied to a value smaller than the initial voltage;
may have
　第４項に記載の質量分析方法、又は第５項若しくは第６項に記載の質量分析装置によれば、大気圧イオン化法による試料のイオン化を行うイオン源（イオン化部）を備えた質量分析装置において、イオン源における試料液体の沸騰及び異常放電の発生を防止して、安定した分析結果を得られるようになる。 According to the mass spectrometry method according to item 4 or the mass spectrometer according to item 5 or 6, a mass spectrometer equipped with an ion source (ionization unit) for ionizing a sample by atmospheric pressure ionization. , the boiling of the sample liquid and the occurrence of abnormal discharge in the ion source can be prevented, and stable analysis results can be obtained.
１１１…イオン化室
１２１…ＥＳＩプローブ
１２３…金属細管
１２５…放電電極
１２６…対電極
１２８…ブロックヒータ
１３１…ＥＳＩ用高電圧電源
１３２…ＡＰＣＩ用高電圧電源
１４４…四重極マスフィルタ
１４５…イオン検出器
１５０…制御部
１５１…分析制御部
１５２…表示制御部
１５３…設定値記憶部
１６１…入力部
１６２…表示部
１７０…データ処理部
１７１…判定部
１８０…ＬＣ
１９１…温度制御部
４２１…スプレーノズル
２８２、３８２、４８２…電流検出部
２８１、３８１、４８１…高電圧電源
３９４…ガスポートヒータ
４９５…ノズルヒータ DESCRIPTION OF SYMBOLS 111... Ionization chamber 121... ESI probe 123... Metal capillary tube 125... Discharge electrode 126... Counter electrode 128... Block heater 131... High voltage power supply for ESI 132... High voltage power supply for APCI 144... Quadrupole mass filter 145... Ion detector Reference Signs List 150 Control unit 151 Analysis control unit 152 Display control unit 153 Setting value storage unit 161 Input unit 162 Display unit 170 Data processing unit 171 Judgment unit 180 LC
Reference Signs List 191 Temperature control unit 421 Spray nozzles 282, 382, 482 Current detectors 281, 381, 481 High voltage power supply 394 Gas port heater 495 Nozzle heater

Claims (6)

  1. 　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
    　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
    　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
    　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
    　を備えた質量分析装置において、前記加熱部による加熱温度を設定する方法であって、
    　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記ノズルから一定組成の試料液体を噴霧している状態において、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流を監視し、
    　前記出力信号又は前記電流の変動幅が予め定められた閾値以上であった場合に、前記加熱温度を前記初期温度よりも低い値に設定する質量分析方法。     an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
    a heating unit that heats the sample liquid sprayed from the nozzle;
    a mass separator that separates ions generated in the ionization unit according to m/z;
    an ion detector that detects the ions separated by the mass separator;
    A method of setting a heating temperature by the heating unit in a mass spectrometer comprising
    The output signal from the ion detector or the current flowing through the ionization electrode is monitored in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and the sample liquid having a constant composition is being sprayed from the nozzle. ,
    A mass spectrometry method, wherein the heating temperature is set to a value lower than the initial temperature when the fluctuation width of the output signal or the current is equal to or greater than a predetermined threshold.
  2. 　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
    　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
    　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
    　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
    　前記加熱部による加熱温度を予め定められた初期温度とした状態で、試料液体の質量分析を実行すべく前記イオン化部、前記加熱部、前記質量分離器、及び前記イオン検出器を制御する制御部と、
    　前記初期温度での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する判定部と、
    　前記判定部によって前記変動幅が予め定められた閾値以上であると判定された場合に、前記加熱温度を前記初期温度よりも低い値に設定するようユーザに通知する通知部と、
    　を有する質量分析装置。     an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
    a heating unit that heats the sample liquid sprayed from the nozzle;
    a mass separator that separates ions generated in the ionization unit according to m/z;
    an ion detector that detects the ions separated by the mass separator;
    A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature. and,
    a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature;
    a notification unit that notifies a user to set the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold;
    A mass spectrometer having
  3. 　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
    　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
    　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
    　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
    　前記加熱部による加熱温度を予め定められた初期温度とした状態で、試料液体の質量分析を実行すべく前記イオン化部、前記加熱部、前記質量分離器、及び前記イオン検出器を制御する制御部と、
    　前記初期温度での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する判定部と、
    　前記判定部によって前記変動幅が予め定められた閾値以上であると判定された場合に、前記加熱温度を前記初期温度よりも低い値に設定する設定部と、
    　を有する質量分析装置。     an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
    a heating unit that heats the sample liquid sprayed from the nozzle;
    a mass separator that separates ions generated in the ionization unit according to m/z;
    an ion detector that detects the ions separated by the mass separator;
    A control unit for controlling the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature. and,
    a determination unit that determines whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold during execution of mass spectrometry at the initial temperature;
    a setting unit that sets the heating temperature to a value lower than the initial temperature when the determination unit determines that the fluctuation range is equal to or greater than a predetermined threshold;
    A mass spectrometer having
  4. 　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
    　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
    　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
    　前記イオン化電極に電圧を印加する高電圧電源と、
    　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
    　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
    　を備えた質量分析装置において、前記イオン化部におけるイオン化パラメータを設定する方法であって、
    　前記加熱部による加熱温度を予め定められた初期温度とし、前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加し、且つ前記ノズルから一定組成の試料液体を噴霧している状態において、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流を監視し、
    　前記出力信号又は前記電流の変動幅が予め定められた閾値以上であった場合に、
    　前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判断し、
    　前記可能性が高いと判断した場合には、前記加熱温度を前記初期温度よりも低い値に設定し、
    　前記可能性が低いと判断した場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定する質量分析方法。     an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
    a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
    a heating unit that heats the sample liquid sprayed from the nozzle;
    a high voltage power supply that applies a voltage to the ionization electrode;
    a mass separator that separates ions generated in the ionization unit according to m/z;
    an ion detector that detects the ions separated by the mass separator;
    A method of setting ionization parameters in the ionization unit in a mass spectrometer comprising
    A state in which the heating temperature of the heating unit is set to a predetermined initial temperature, a predetermined initial voltage is applied from the high voltage power source to the ionization electrode, and a sample liquid having a constant composition is sprayed from the nozzle. , monitoring the output signal from the ion detector or the current flowing through the ionization electrode;
    When the variation width of the output signal or the current is equal to or greater than a predetermined threshold,
    determining whether the possibility that the sample liquid is boiling is high or low based on at least one of the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid;
    If it is determined that the possibility is high, the heating temperature is set to a value lower than the initial temperature,
    A mass spectrometry method, wherein, when the possibility is determined to be low, the absolute value of the voltage applied from the high-voltage power supply to the ionization electrode is set to a value smaller than the initial voltage.
  5. 　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
    　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
    　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
    　前記イオン化電極に電圧を印加する高電圧電源と、
    　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
    　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
    　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加した状態で、試料液体の質量分析を実行すべく前記イオン化部、前記試料液体供給部、前記加熱部、前記高電圧電源、前記質量分離器、及び前記イオン検出器を制御する制御部と、
    　前記初期温度且つ前記初期電圧での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する第１の判定を行い、前記第１の判定において前記変動幅が前記閾値以上であると判定した場合には、更に、前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判定する第２の判定を行う判定部と、
    　前記可能性が高いと判断された場合には、前記加熱温度を前記初期温度よりも低い値に設定するようユーザに通知し、前記可能性が低いと判断された場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定するようユーザに通知する通知部と、
    　を有する質量分析装置。     an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
    a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
    a heating unit that heats the sample liquid sprayed from the nozzle;
    a high voltage power supply that applies a voltage to the ionization electrode;
    a mass separator that separates ions generated in the ionization unit according to m/z;
    an ion detector that detects the ions separated by the mass separator;
    the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector;
    determining whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of mass spectrometry at the initial temperature and the initial voltage; Determination 1 is performed, and if it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid are further determined. a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of
    If the possibility is determined to be high, the user is notified to set the heating temperature to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply a notification unit for notifying the user to set the absolute value of the voltage applied to the ionization electrode from to a value smaller than the initial voltage;
    A mass spectrometer having
  6. 　試料液体を噴霧するノズルとイオン化電極とを有し、大気圧イオン化法によって前記試料液体中の化合物をイオン化するイオン化部と、
    　前記ノズルに前記試料液体を連続的に供給する試料液体供給部と、
    　前記ノズルから噴霧された前記試料液体を加熱する加熱部と、
    　前記イオン化電極に電圧を印加する高電圧電源と、
    　前記イオン化部で発生したイオンをｍ／ｚに応じて分離する質量分離器と、
    　前記質量分離器で分離された前記イオンを検出するイオン検出器と、
    　前記加熱部による加熱温度を予め定められた初期温度とし、且つ前記高電圧電源から前記イオン化電極に予め定められた初期電圧を印加した状態で、試料液体の質量分析を実行すべく前記イオン化部、前記試料液体供給部、前記加熱部、前記高電圧電源、前記質量分離器、及び前記イオン検出器を制御する制御部と、
    　前記初期温度且つ前記初期電圧での質量分析の実行中に、前記イオン検出器からの出力信号又は前記イオン化電極に流れる電流の変動幅が予め定められた閾値以上であるか否かを判定する第１の判定を行い、前記第１の判定において前記変動幅が前記閾値以上であると判定した場合には、更に、前記加熱温度、前記試料液体の流量、及び前記試料液体中の有機溶媒比率のうちの少なくとも１つに基づいて前記試料液体が沸騰している可能性が高いか低いかを判定する第２の判定を行う判定部と、
    　前記可能性が高いと判断された場合には、前記加熱温度を前記初期温度よりも低い値に設定し、前記可能性が低いと判断された場合には、前記高電圧電源から前記イオン化電極に印加する電圧の絶対値を前記初期電圧よりも小さい値に設定する設定部と、
    　を有する質量分析装置。     an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing a compound in the sample liquid by atmospheric pressure ionization;
    a sample liquid supply unit that continuously supplies the sample liquid to the nozzle;
    a heating unit that heats the sample liquid sprayed from the nozzle;
    a high voltage power supply that applies a voltage to the ionization electrode;
    a mass separator that separates ions generated in the ionization unit according to m/z;
    an ion detector that detects the ions separated by the mass separator;
    the ionization unit for mass spectrometry of the sample liquid in a state in which the heating temperature of the heating unit is set to a predetermined initial temperature and a predetermined initial voltage is applied from the high voltage power source to the ionization electrode; a control unit that controls the sample liquid supply unit, the heating unit, the high voltage power supply, the mass separator, and the ion detector;
    determining whether or not a fluctuation range of the output signal from the ion detector or the current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of mass spectrometry at the initial temperature and the initial voltage; Determination 1 is performed, and if it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, the heating temperature, the flow rate of the sample liquid, and the organic solvent ratio in the sample liquid are further determined. a determination unit that performs a second determination to determine whether the possibility that the sample liquid is boiling is high or low based on at least one of
    If the possibility is determined to be high, the heating temperature is set to a value lower than the initial temperature, and if the possibility is determined to be low, the high voltage power supply to the ionization electrode a setting unit that sets the absolute value of the voltage to be applied to a value smaller than the initial voltage;
    A mass spectrometer having
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US20200203141A1 (en) * 2018-12-21 2020-06-25 Thermo Finnigan Llc Apparatus and System for Active Heat Transfer Management in Ion Sources

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200203141A1 (en) * 2018-12-21 2020-06-25 Thermo Finnigan Llc Apparatus and System for Active Heat Transfer Management in Ion Sources

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