JP7513216B2 - Mass spectrometry method and mass spectrometry device - Google Patents

Description

The present invention relates to a mass spectrometry method, and in particular to a method for setting ionization parameters in a mass spectrometry device.

Various ionization methods are known for ionizing samples in mass spectrometers. These ionization methods can be broadly divided into methods that perform ionization under a vacuum atmosphere and methods that perform ionization under an atmosphere at approximately atmospheric pressure, the latter of which is generally referred to as atmospheric pressure ionization (API).

As atmospheric pressure ionization methods, electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are widely used. In both of these ionization methods, a sample liquid (e.g., a mixture of a sample to be analyzed and a solvent) is sprayed from a nozzle into an atmospheric pressure atmosphere. In ESI, a high voltage is applied to a metal capillary provided in the nozzle, which charges the sample liquid and sprays it, thereby ionizing the sample molecules. On the other hand, in APCI, a corona discharge is generated by applying a high voltage to a needle-shaped discharge electrode provided near the nozzle. Then, the solvent molecules in the sample liquid sprayed from the nozzle are ionized by the corona discharge, and the sample molecules are ionized by an ion-molecule reaction between the generated solvent ions and the sample molecules.

Republished No. 2018/100612

In the atmospheric pressure ionization method described above, the sample liquid sprayed from the nozzle is heated by providing a heater at the tip of the nozzle or by spraying high-temperature gas onto the spray from the nozzle, thereby promoting the vaporization of the solvent in the sample liquid (see, for example, Patent Document 1). However, if the heating temperature is too high, the sample liquid boils, which may result in unstable ionization of the sample molecules and make it difficult to obtain stable analysis results.

The present invention has been made in consideration of the above points, and its object is to provide a mass spectrometer equipped with an ion source that ionizes a sample by atmospheric pressure ionization, capable of preventing boiling of the sample liquid in the ion source and obtaining stable analysis results.

The mass spectrometry method according to the present invention, which has been made to solve the above problems, comprises:
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
A method for setting a heating temperature by the heating unit in a mass spectrometer comprising:
a heating temperature of the heating unit is set to a predetermined initial temperature, and a sample liquid having a constant composition is sprayed from the nozzle, while monitoring an output signal from the ion detector or a current flowing through the ionization electrode;
When the fluctuation range of the output signal or the current is equal to or greater than a predetermined threshold value, the heating temperature is set to a value lower than the initial temperature.

In order to solve the above problems, 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 compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass analysis of the sample liquid while 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 an output signal from the ion detector or a current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of the 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 value;
It has the following.

In order to solve the above problems, the mass spectrometer according to the present invention comprises:
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass analysis of the sample liquid while 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 an output signal from the ion detector or a current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of the 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 value;
The present invention may also have the following structure.

The mass spectrometry method according to the present invention further comprises:
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
A method for setting ionization parameters in an ionization unit in a mass spectrometer comprising:
a heating temperature by the heating unit is set to a predetermined initial temperature, a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode, and a sample liquid having a constant composition is sprayed from the nozzle, while monitoring an output signal from the ion detector or a current flowing through the ionization electrode;
When the fluctuation range of the output signal or the current is equal to or greater than a predetermined threshold value,
determining whether the sample liquid is likely to be boiling based on at least one of the heating temperature, the flow rate of the sample liquid, and the ratio of the organic solvent 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,
If it is determined that the possibility is low, the absolute value of the voltage applied from the high voltage power supply to the ionization electrode may be set to a value smaller than the initial voltage.

Furthermore, the mass spectrometer according to the present invention comprises:
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the sample liquid supply unit, the heating unit, the high-voltage power supply, the mass separator, and the ion detector to perform mass analysis of the sample liquid while setting the heating temperature by the heating unit to a predetermined initial temperature and applying a predetermined initial voltage from the high-voltage power supply to the ionization electrode;
a determination unit that performs a first determination to determine whether or not a fluctuation range of an output signal from the ion detector or a 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, and when it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, further performs a second determination to determine whether or not it is highly likely that the sample liquid is boiling 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;
a notification unit that notifies a user to set the heating temperature to a value lower than the initial temperature when it is determined that the possibility is high, and that notifies a user to set an absolute value of the voltage applied from the high voltage power supply to the ionization electrode to a value lower than the initial voltage when it is determined that the possibility is low;
The present invention may also have the following structure.

Furthermore, the mass spectrometer according to the present invention comprises:
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the sample liquid supply unit, the heating unit, the high-voltage power supply, the mass separator, and the ion detector to perform mass analysis of the sample liquid while setting the heating temperature by the heating unit to a predetermined initial temperature and applying a predetermined initial voltage from the high-voltage power supply to the ionization electrode;
a determination unit that performs a first determination to determine whether or not a fluctuation range of an output signal from the ion detector or a 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, and when it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, further performs a second determination to determine whether or not it is highly likely that the sample liquid is boiling 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;
a setting unit that sets the heating temperature to a value lower than the initial temperature when it is determined that the possibility is high, and sets an absolute value of the voltage applied from the high voltage power supply to the ionization electrode to a value lower than the initial voltage when it is determined that the possibility is low;
The present invention may also have the following structure.

According to the mass spectrometry method or mass spectrometry apparatus of the present invention, in a mass spectrometry apparatus equipped with an ion source (ionization section) that ionizes a sample by atmospheric pressure ionization, boiling of the sample liquid in the ion source can be prevented, thereby making it possible to obtain stable analysis results.

1 is a schematic diagram of an LC-MS including a mass spectrometer according to one embodiment of the present invention. FIG. 2 is a schematic configuration diagram of the periphery of an ionization chamber in the mass spectrometer. 6 is a flowchart showing a first example of a procedure for setting ionization parameters in the embodiment. 10 is a flowchart showing a second example of a procedure for setting ionization parameters in the embodiment. 10 is a flowchart showing a third example of a procedure for setting ionization parameters in the embodiment. 10 is a flowchart showing a fourth example of a procedure for setting ionization parameters in the embodiment. FIG. 4 is a schematic diagram showing another example of the configuration of the mass spectrometer in the embodiment. FIG. 4 is a schematic diagram showing yet another configuration example of the mass spectrometer in the same embodiment. FIG. 13 is a schematic diagram showing still another configuration example of the mass spectrometer in the same embodiment.

Hereinafter, a mass spectrometer according to an embodiment of the present invention and a method for setting ionization parameters thereof will be described with reference to the drawings. FIG. 1 is a schematic diagram of a liquid chromatograph mass spectrometer (LC-MS) including a mass spectrometer according to this embodiment, and FIG. 2 is a schematic diagram showing the configuration of the ionization chamber and the surroundings of the mass spectrometer. The mass spectrometer according to this embodiment performs mass analysis on a sample liquid eluted from a column of a liquid chromatograph (hereinafter referred to as LC) 180, and includes a measurement unit 110 that performs mass analysis and collects data, a data processing unit 170 that processes the data collected by the measurement unit 110, and a control unit 150 that controls the measurement unit 110. The LC 180 corresponds to the sample liquid supply unit in the present invention. In addition, an input unit 161, which is a pointing device such as a mouse or a keyboard operated by a user (analyst), and a display unit 162 such as a liquid crystal display are connected to the control unit 150.

As shown in FIG. 1, the LC 180 includes a first liquid delivery pump 183, a second liquid delivery pump 184, a mixer 185, an injector 186, and a column 187. The first liquid delivery pump 183 draws in mobile phase A (e.g., organic solvent) from the first mobile phase container 181 and delivers it at a predetermined flow rate, and the second liquid delivery pump 184 draws in mobile phase B (e.g., water) from the second mobile phase container 182 and delivers it at a predetermined flow rate. Mobile phase A and mobile phase B are mixed in the mixer 185 and delivered to the column 187 via the injector 186. In the injector 186, the sample to be analyzed is injected into the mobile phase using a microsyringe or the like, and the sample is delivered to the 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 are eluted from the outlet end of the column 187 with a time lag.

The eluate from the column 187 is sent to a mass spectrometer as a detector. The measurement section 110 of the mass spectrometer includes an ionization chamber 111 (corresponding to the ionization section in the present invention) that is in an approximately atmospheric pressure atmosphere, an analysis chamber 114 that is maintained in a high vacuum atmosphere by a high-performance vacuum pump (not shown), and a first intermediate vacuum chamber 112 and a second intermediate vacuum chamber 113 that are located between the ionization chamber 111 and the analysis chamber 114 and have a stepwise increasing degree of vacuum. In other words, the measurement section 110 in this embodiment has a multi-stage differential pumping system configuration. The ionization chamber 111 and the first intermediate vacuum chamber 112 are connected through a small-diameter ion introduction tube 129.

In this embodiment, the ionization chamber 111 simultaneously performs electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). On the wall of the ionization chamber 111, an ESI probe 121, which is a spray nozzle that electrostatically sprays the sample liquid into the ionization chamber 111, and a needle-shaped discharge electrode (corona needle) 125 that generates a corona discharge in the ionization chamber 111 are arranged. As shown in FIG. 2, the ESI probe 121 includes a capillary 122 through which the sample liquid is supplied, a metal capillary 123 through which the capillary 122 is inserted, and a nebulizer gas tube 124 that is approximately coaxial with the capillary 122 and the metal capillary 123. The capillary 122 is, for example, a glass capillary, and its rear end is connected to the outlet end of a column 187 provided in the LC 180. The rear end of the nebulizer gas tube 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 a predetermined length from the tip of the nebulizer gas tube 124. An ESI high voltage power supply 131 is connected to the metal capillary 123.

The above-mentioned discharge electrode 125 is disposed ahead of the direction of travel of the spray flow from the ESI probe 121, and the discharge electrode 125 is connected to the APCI high voltage power supply 132. Hereinafter, the metal capillary 123 of the ESI probe 121 and the discharge electrode 125 may be collectively referred to as the "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 supplies in the present invention.

The inlet end of the ion introduction tube 129 is also arranged in front of the direction of travel of the nebulized 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 the heating unit in the present invention) for heating the ion introduction tube 129 and the dry gas supply tube 115 described later is provided. Furthermore, at the boundary between the ionization chamber 111 and the first intermediate vacuum chamber 112, a plate-shaped counter electrode 126 is arranged, and a dry gas outlet 127 is provided at the center of the counter electrode 126. From the dry gas outlet 127, dry gas (heated 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 tube 115 is ejected toward the nebulized flow from the ESI probe 121. Furthermore, the measurement unit 110 is provided with a temperature control unit 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.

The first intermediate vacuum chamber 112 and the second intermediate vacuum chamber 113 are respectively provided with ion guides 141, 143 that focus ions while transporting them to the rear stage, and the first intermediate vacuum chamber 112 and the second intermediate vacuum chamber 113 are separated by a skimmer 142 with a small hole at the top. In addition, the analysis chamber 114 is provided with a quadrupole mass filter 144 (corresponding to the mass separator in this invention) that separates ions according to m/z, and an ion detector 145 that detects ions that have passed through the quadrupole mass filter 144. Note that the configuration of each part can be changed as appropriate, such as by replacing the quadrupole mass filter 144 with an orthogonal acceleration time-of-flight mass analyzer.

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 memory unit 153 that stores the setting values of various analysis conditions. The analysis control unit 151 performs analysis of a sample by LC-MS by controlling the ESI high voltage power supply 131, the APCI high voltage power supply 132, and other power supplies (not shown, for example, those that apply voltage to the ion guides 141, 143 or the quadrupole mass filter 144, etc.), the temperature control unit 191, and the first liquid delivery pump 183 and the second liquid delivery pump 184 of the LC 180. The display control unit 152 displays information input and set by the user, the results of mass analysis, various notifications, etc. on the display unit 162.

The data processing unit 170 has a judgment unit 171 as a functional block characteristic of the present invention.

In addition, at least a part of the functions of the control unit 150 and the data processing unit 170 can be realized by using a general-purpose personal computer equipped with a CPU, memory, and a large-capacity storage device such as a hard disk drive (HDD) or a solid-state drive (SSD) as the hardware resource, and executing dedicated software pre-installed on the computer on the computer.

First, the basic analysis operation of the mass spectrometer according to this embodiment will be described. The eluate from the LC 180, i.e., a mixture of the sample components separated by the column 187 provided in the LC 180 and the solvent (mobile phase), is introduced as the sample liquid into the rear end of the capillary 122 provided in the ESI probe 121. In addition, a high voltage generated by the high voltage power supply 131 for ESI is applied to the metal capillary 123 of the ESI probe 121, and a high voltage generated by the high voltage power supply 132 for APCI 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 is sprayed as charged droplets from the tip of the ESI probe 121 with the help of nebulizing gas ejected from the nebulizing gas tube 124, which is the outer tube of the capillary 122.

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 stream from the ESI probe 121. This causes the solvent in the charged droplets to rapidly evaporate, reducing the droplet size, and gas ions are generated by Coulomb repulsion. The ions generated at this time are mainly derived from medium to high polarity components in the sample.

Furthermore, a corona discharge is generated around the tip of the discharge electrode 125 by application of a voltage by the APCI high voltage power supply 132. This corona discharge ionizes the solvent molecules in the spray stream to generate reactive ions. These reactive ions then react with the sample molecules in the spray stream (ion-molecule reaction), ionizing the sample molecules. The ions generated at this time are mainly derived from low to medium polarity components in the sample.

The sample-derived ions (sample ions) thus generated are drawn 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. In addition, some of the tiny droplets that remain in the ionization chamber 111 and are not completely evaporated are also drawn into the ion introduction tube 129, where they are heated by the block heater 128 to evaporate the solvent and promote ionization. The ions that reach the first intermediate vacuum chamber 112 are focused by the ion guide 141 and sent to the subsequent second intermediate vacuum chamber 113 and analysis chamber 114.

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. Then, the ions that pass through the quadrupole mass filter 144 reach the ion detector 145. In the ion detector 145, a current corresponding to the number of ions that reach the detector is extracted as an ion detection signal. The ion detection signal is digitized by the A/D converter 146 and sent to the data processing unit 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 perform qualitative analysis of unknown compounds or quantitative analysis of target compounds.

Next, a characteristic operation of the mass spectrometer according to this embodiment will be described. In the mass spectrometer according to this embodiment, a setting operation is performed to optimize the ionization parameters prior to performing the analysis (mass analysis to obtain the final analysis result of the sample to be analyzed). In the following, it is assumed that the temperature setting of the block heater 128 is performed as the ionization parameter, and that other ionization parameters (for example, the voltage applied to the ionization electrode) have already been set to optimal values.

This setting operation is performed while continuously supplying a standard sample of a 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 present analysis, and a sample liquid consisting of only a solvent that does not substantially contain sample components, for example, a mobile phase used in the LC 180, is used as the standard sample. In addition, in the setting operation of the ionization parameters, the analysis control unit 151 controls the high voltage power supply 131 for ESI and the high voltage power supply 132 for APCI, as well as a power supply not shown, to apply the same voltage (i.e., a voltage of an optimal value determined in advance) as that during the execution of the present analysis to the metal capillary 123, discharge electrode 125, and ion guides 141 and 143 of the ESI probe 121. In addition, the voltage applied to the rod electrodes constituting the quadrupole mass filter 144 is controlled so that ions derived from the known components pass through the quadrupole mass filter 144. In addition, in the setting of the applied voltage, the gas supplied from gas source 130 to nebulizer gas tube 124 and drying gas nozzle 127 has the same composition as the gas used when carrying out this analysis.

The procedure for setting the ionization parameters (i.e., setting the temperature of the block heater 128) will be explained with reference to the flowchart of Figure 3.

First, the user performs a predetermined operation on the input unit 161 to instruct the analysis control unit 151 to start the analysis of 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, and the application of voltage to the metal capillary 123 and the discharge electrode 125, the supply of nebulizing gas and dry gas from the gas source 130, and the heating of the dry gas by the block heater 128 are started (step 11). At this time, a predetermined initial temperature is applied as the heating temperature by the block heater 128. As the initial temperature, for example, a general value as a temperature applied to the analysis of the sample is set in advance by the manufacturer or user of the mass spectrometer and stored in the set value memory unit 153. When the 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 approximately 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 this embodiment, the judgment unit 171 monitors the ion detection signal from the ion detector 145, and judges whether the fluctuation width of the ion detection signal is equal to or greater than a predetermined threshold value at a time point when a predetermined time has elapsed since the start of the analysis of the standard sample (step 12). At this time, if the fluctuation width of the ion detection signal is below the threshold value (i.e., if the answer is No in step 12), the set temperature (i.e., the initial temperature) of the block heater 128 at this time is determined as the temperature to be applied to this analysis, and the value is stored in the set value storage unit 153 (step 14).

On the other hand, if the fluctuation range of the ion detection signal is equal to or greater than the threshold (i.e., if Yes in step 12), the judgment unit 171 judges that boiling of the sample liquid is occurring in the ionization chamber 111, and outputs a signal indicating this to the analysis control unit 151. The analysis control unit 151, which has received the signal, lowers the heating temperature of the block heater 128 by a predetermined temperature range (step 13). Thereafter, the process returns to step 12, and the processes of steps 12 to 13 are repeatedly executed until it is judged that the fluctuation range of the ion detection signal is below the threshold (i.e., until No in step 12). Then, when it is judged that the fluctuation range 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 this analysis, and the value is stored in the set value storage unit 153 (step 14). That is, in this embodiment, the analysis control unit 151 and the set value storage unit 153 correspond to the setting unit in the present invention.

After the temperature setting of the block heater 128 is completed, the sample to be analyzed is injected from the injector 186 of the LC 180, and the sample to be analyzed is separated by the column 187 and mass analyzed (main analysis) by the measurement unit 110. At this time, the analysis control unit 151 reads out the temperature setting value of the block heater 128 (determined in step 14 above) stored in the setting value memory unit 153, and controls the block heater 128 based on the temperature setting value. This allows the sample to be ionized at the optimal heating temperature set by the setting work. As a result, boiling of the sample liquid in the ionization chamber 111 is suppressed, and the ionization state in the ionization chamber 111 is stabilized, allowing mass analysis results with a high S/N ratio (i.e., mass spectrum, mass chromatogram, or total ion chromatogram, etc.) to be obtained.

In the above example, the set temperature of the block heater 128 is automatically lowered when boiling of the sample liquid is detected by the determination unit 171, but instead, the user may be notified to lower the set temperature. The operation of the control unit 150 and data processing unit 170 in such a case is shown in FIG. 4. In the flowchart of FIG. 4, the process up to the determination of whether the fluctuation range of the ion detection signal is equal to or greater than the threshold value (i.e., steps 21-22) is the same as steps 11-12 in the flowchart of FIG. 3 above, and therefore will not be described here.

In step 22 of the flowchart in FIG. 4, when the judgment unit 171 judges that the fluctuation range of the ion detection signal is equal to or greater than the threshold (hence, the sample liquid is likely to be boiling), the display control unit 152 causes the display unit 162 to display a predetermined notification screen (step 23). This notification screen displays a message urging the user to lower the heating temperature by the block heater 128. That is, in this example, the display control unit 152 and the display unit 162 correspond to the notification unit in the present invention. After checking the notification screen, the user operates the input unit 161 to instruct the control unit 150 to set the heating temperature by the block heater 128 to a value lower than the initial temperature. The control unit 150, upon receiving the instruction, stores a value lower than the initial temperature by a predetermined temperature range in the set value storage unit 153 as the set temperature to be applied to this 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 this analysis.

The ionization parameter setting method for a mass spectrometer according to the present invention can also be applied to a mass spectrometer that does not include the above-mentioned determination unit 171. In that case, after starting the analysis of the standard sample in step 11 of FIG. 3, the data processing unit 170 generates a waveform (i.e., a mass chromatogram or a total ion chromatogram) showing the time change of the ion detection signal, and the display control unit 152 displays the waveform on the display unit 162. Then, when the user visually checks the waveform for a predetermined time and determines that the fluctuation range of the ion detection signal is equal to or greater than a predetermined threshold (hence, the sample liquid is likely to be boiling) (i.e., Yes in step 12), the user operates the input unit 161 to instruct the analysis control unit 151 to set the heating temperature by the block heater 128 to a predetermined value lower than the current value (step 13). Thereafter, steps 12 and 13 are repeated until the user determines that the fluctuation range of the ion detection signal displayed on display unit 162 has fallen below the threshold, and at the point in time when the user determines that the fluctuation range of the ion detection signal has fallen below the threshold (and therefore that the possibility that the sample liquid is boiling has decreased), the user operates input unit 161 to instruct control unit 150 to set the heating temperature by block heater 128 at that time as the temperature to be applied to the analysis (step 14).

In the method for setting ionization parameters shown in the flowcharts of Figures 3 and 4, the ionization parameters other than the temperature of the block heater 128 are optimized in advance, but the method for setting ionization parameters according to the present invention is not limited to this, and in addition to the temperature of the block heater 128, the voltage applied to the ionization electrodes (i.e., the metal capillary 123 of the ESI probe 121 and the discharge electrode 125) may also be optimized. The method for setting ionization parameters in such a case is described below.

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 the sample is ionized. If the voltage value at this time is too large, an undesirable discharge (abnormal discharge) may occur in the ion source, causing the ionization of the sample molecules to become unstable. In the following example, when it is determined that the ionization of the sample molecules is unstable based on the fluctuation width of the ion detection signal, it is determined whether the cause is a high heating temperature of the block heater 128 or a high voltage applied to the ionization electrode, and the heating temperature is lowered or the applied voltage is reduced depending on the result. 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 reducing the value of the applied voltage means that the absolute value of the applied voltage is reduced without changing the positive or negative sign of the applied voltage.

The specific procedure for the setting work will be described with reference to the flowchart of FIG. 5. First, the user performs a predetermined operation on the input unit 161 to instruct the analysis control unit 151 to start the analysis of the standard sample. This starts the analysis of the standard sample under the control of the analysis control unit 151 (step 31). Specifically, the analysis control unit 151 controls the first liquid delivery pump 183 and the second liquid delivery pump 184 of the LC 180, and mobile phase A (organic solvent) is delivered from the first mobile phase container 181 at a predetermined flow rate, and 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 the mixer 185 at a predetermined mixing ratio determined by the flow rate of the first liquid delivery pump 183 and the flow rate of the second liquid delivery pump 184, and delivered to the column 187. At this time, the flow rate of the first liquid delivery pump 183 and the flow rate of the second liquid delivery pump 184 are respectively applied with values previously stored in the set value storage unit 153 by the user as flow rates to be applied to this analysis. In addition, under the control of the analysis control unit 151, the measurement unit 110 starts applying a voltage from the ESI high voltage power supply 131 to the metal capillary tube 123 of the ESI probe 121, applying a voltage from the APCI high voltage power supply 132 to the discharge electrode 125, supplying the nebulizing gas and the dry gas from the gas source 130, and heating the dry gas by the block heater 128. At this time, a predetermined initial temperature is applied as the heating temperature by the block heater 128, and a predetermined initial voltage 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. 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. The initial temperature and initial voltage are, for example, typical values of temperature and voltage applied to sample analysis, which are set in advance by the manufacturer or user of the mass spectrometer and stored in the set value storage unit 153 .

After the mass analysis 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 and determines whether the fluctuation range of the ion detection signal is equal to or greater than a predetermined threshold value when a predetermined time has elapsed since the start of the mass analysis (step 32). If the fluctuation range of the ion detection signal is below the threshold value (i.e., No in step 32), the set temperature (i.e., initial temperature) of the block heater 128 and the applied voltage (i.e., initial voltage) by the ESI high voltage power supply 131 and the APCI high voltage power supply 132 are determined as values to be applied to this analysis, and these values are stored in the set value storage unit 153 (step 40).

On the other hand, if the fluctuation range of the ion detection signal is equal to or greater than the threshold value (i.e., if the answer is Yes in step 32), the judgment unit 171 judges that the ionization of the sample molecules in the ionization chamber 111 has become unstable, and first judges whether this is due to boiling of the sample liquid. It is known that boiling of the sample liquid is likely to occur when the heating temperature by the block heater 128 is high (e.g., when the temperature is equal to or greater than the boiling point of the mobile phase solvent), when the organic solvent ratio of the mobile phase is high (e.g., when the mobile phase flow rate is low (e.g., when the flow rate is 1 mL/min or less). Therefore, the judgment unit 171 refers to various set values of the LC 180 stored in the set value storage unit 153, and judges whether the initial temperature is equal to or higher than a predetermined threshold value (step 33), whether the ratio of the organic solvent in the mobile phase (in the above example, the ratio of the "flow rate of the first liquid feed pump 183" to the "sum of the flow rate of the first liquid feed pump 183 and the second liquid feed pump 184") is equal to or higher than a predetermined threshold value (step 34), and whether the flow rate of the mobile phase (in the above example, the sum of the flow rate of the first liquid feed pump 183 and the second liquid feed pump 184) is equal to or lower than a threshold value (step 35). If any one of steps 33 to 35 is Yes, it judges that there is a high possibility that the sample liquid is boiling at that time, and sends a signal indicating this to the analysis control unit 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 reduces the heating temperature by the block heater 128 by a predetermined temperature range (step 38). Then, it is again determined whether the fluctuation range of the ion detection signal is equal to or greater than the predetermined threshold value (step 39). Thereafter, the processes of steps 38 to 39 are repeatedly executed until it is determined in step 39 that the fluctuation range of the ion detection signal is below the threshold value (i.e., until step 39 is No). When it is determined that the fluctuation range of the ion detection signal is below the threshold value, the set temperature value of the block heater 128 and the applied voltage values by the ESI high voltage power supply 131 and the APCI high voltage power supply 132 at that time are determined as the temperatures to be applied to this analysis, and these values are stored in the set value storage unit 153 (step 40).

On the other hand, if all of steps 33 to 35 are No, the cause of the large fluctuation range of the ion detection signal (i.e., the ionization of the sample molecules is unstable) is considered to be due to the occurrence of abnormal discharge in the ionization chamber 111, not the boiling of the sample solution. Therefore, in this case, the judgment unit 171 sends a signal indicating this to the analysis control unit 151, and the analysis control unit 151 that receives the signal reduces the applied voltages by the ESI high voltage power supply 131 and the APCI high voltage power supply 132 by a predetermined voltage range (step 36). The voltage range may be different or the same for the ESI high voltage power supply 131 and the APCI high voltage power supply 132. Then, it is again determined whether the fluctuation range of the ion detection signal is equal to or greater than the predetermined threshold value (step 37). Thereafter, the processes of steps 36 to 37 are repeatedly executed until it is determined in step 37 that the fluctuation range of the ion detection signal is below the threshold value (i.e., until step 37 becomes No). Then, when it is determined that the fluctuation range of the ion detection signal falls below the threshold value, the values of the applied voltages 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 determined as the values to be applied to this analysis, and these values are stored in the set value memory unit 153 (step 40).

After the ionization parameter setting work is completed as described above, the sample to be analyzed is injected from the injector 186 of the LC 180 and mass analysis (main analysis) of the sample to be analyzed is performed. At this time, the analysis control unit 151 controls the first liquid delivery pump 183 and the second liquid delivery pump 184 to deliver mobile phase A and mobile phase B at the same flow rate as when the ionization parameters were set. The analysis control unit 151 also 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 memory unit 153, and controls the block heater 128, the high voltage power supply for ESI 131, and the high voltage power supply for APCI 132 based on the set value. This allows the ionization of the sample to be analyzed to be performed at the optimal heating temperature and applied voltage set by the setting work. As a result, boiling of the solvent and the occurrence of abnormal discharge in the ionization chamber 111 are suppressed, and the ionization state in the ionization chamber 111 is stabilized, making it possible to obtain mass analysis results (i.e., mass spectrum, mass chromatogram, total ion chromatogram, etc.) with a high signal-to-noise ratio.

In the example of FIG. 5, the set temperature of the block heater 128 is automatically lowered and the applied voltage to the ionization electrode is automatically reduced depending on the result of the judgment by the judgment unit 171. Alternatively, the user may be notified to lower the set temperature or reduce the applied voltage. The operation of the control unit 150 and the data processing unit 170 in such a case is shown in FIG. 6. In the flowchart of FIG. 6, the process up to the determination of whether the fluctuation range of the ion detection signal is equal to or greater than the threshold value (i.e., steps 41-42) is the same as steps 31-32 in the flowchart of FIG. 5, and therefore will not be described here.

In step 42 of the flowchart in FIG. 6, if the fluctuation range of the ion detection signal is below the threshold value (i.e., No in step 42), the set temperature (i.e., initial temperature) of the block heater 128 at this time and the applied voltage (i.e., initial voltage) by the ESI high voltage power supply 131 and the APCI high voltage power supply 132 are determined as the values to be applied to this analysis, and these values are stored in the set value memory unit 153 (step 47).

On the other hand, if it is determined in step 42 that the fluctuation width of the ion detection signal is equal to or greater than the threshold (i.e., if the answer is Yes in step 42), the determination unit 171 first determines in order whether the initial temperature is equal to or greater than a predetermined threshold (step 43), whether the organic solvent ratio in the mobile phase is equal to or greater than a predetermined threshold (step 44), and whether the flow rate of the mobile phase is equal to or less than a threshold (step 45). If any one of steps 43 to 45 is Yes, it determines that the sample liquid is likely to be boiling at that point in time and sends a signal indicating this to the display control unit 152. Note that steps 33 to 35 may be performed in any order, not limited to the above. The display control unit 152 that receives the signal causes a predetermined notification screen to be displayed on the display unit 162 (step 48). This notification screen displays at least a message urging the user to lower the set temperature of the block heater 128. The user who has confirmed the notification screen operates the input unit 161 to instruct the control unit 150 to set the set temperature of the block heater 128 to a value smaller than the initial temperature. The control unit 150 that has received the instruction stores a value that is lower than the initial temperature by a predetermined temperature width as the set temperature to be applied to the present analysis in the set value storage unit 153. 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 present analysis.

On the other hand, if all of steps 43 to 45 are No, the judgment unit 171 sends a signal indicating that to the display control unit 152, and the display control unit 152, which has received the signal, causes the display unit 162 to display a predetermined notification screen (step 46). This notification screen displays a message urging the user to lower at least the voltage applied to the metal capillary 123 of the ESI probe 121, the voltage applied to the discharge electrode 125, or both. After checking the notification screen, the user operates the input unit 161 to instruct the control unit 150 to set the set value of the voltage applied to the metal capillary 123 of the ESI probe 121, the set value of the voltage applied to the discharge electrode 125, or both, to a value smaller than the initial voltage. The control unit 150, which has received the instruction, stores a value smaller than the initial voltage by a predetermined voltage width in the set value storage unit 153 as the voltage value to be applied to this analysis. Alternatively, the user may input a voltage value smaller than the initial voltage through 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.

In the example shown in the flowcharts of Figures 5 and 6, steps 32 and 42 correspond to the "first judgment" in the present invention, and steps 33 to 35 and steps 43 to 45 correspond to the "second judgment" in the present invention.

The method of setting ionization parameters as shown in FIG. 5 can also be applied to a mass spectrometer that does not have the above-mentioned judgment unit 171. In that case, after starting the analysis of the standard sample in step 31 of FIG. 5, the data processing unit 170 generates a waveform showing the time change of the ion detection signal, and the display control unit 152 displays the waveform on the display unit 162. Then, when the user visually checks the waveform for a predetermined time and determines that the fluctuation range of the ion detection signal is equal to or greater than a predetermined threshold (i.e., Yes in step 32), the user operates the input unit 161 to instruct the control unit 150 to display various settings related to the LC-MS of this embodiment. The control unit 150 that has received the instruction refers to the various settings stored in the setting value storage unit 153, and based on them, displays the heating temperature by the block heater 128, the organic solvent ratio of the mobile phase, and the flow rate of the mobile phase on the display unit 162. The organic solvent ratio and the mobile phase flow rate can be calculated from, for example, the set value of the flow rate of the first liquid feed pump 183 and the set value of the flow rate of the second liquid feed pump stored in the set value storage unit 153. The user checks these values displayed on the display unit 162, and when the user determines that the heating temperature of the block heater 128 is equal to or higher than a predetermined threshold, that the organic solvent ratio of the mobile phase is equal to or higher than a predetermined threshold, or that the mobile phase flow rate is equal to or lower than a predetermined threshold (i.e., when any of steps 33 to 35 is Yes), the user determines that boiling of the sample liquid is occurring in the ionization chamber 111, and instructs 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 38). Thereafter, steps 38 to 39 are repeated until the user judges that the fluctuation range of the ion detection signal displayed on the display unit 162 falls below the threshold (i.e., until step 39 becomes Yes), and at the point in time when it is judged that the fluctuation range falls below the threshold, the user operates the input unit 161 to instruct the control unit 150 to set the heating temperature value 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 this analysis (step 40). The control unit 150, which has received the instruction, stores the values in the set value storage unit 153. On the other hand, if the user judges that all of steps 33 to 35 are No, it is judged that an abnormal discharge has occurred in the ionization chamber 111, and the voltages applied by the ESI high voltage power supply 131 and the APCI high voltage power supply 132 are each reduced by a predetermined voltage range (step 36). Thereafter, steps 36 to 37 are repeated until it is determined that the fluctuation range of the ion detection signal is below the threshold (i.e., until step 37 is No), and at the point in time when it is determined that the fluctuation range is below the threshold, the user performs a predetermined operation on input unit 161 to instruct control unit 150 to set the heating temperature value of block heater 128 and the value of the voltage applied to the ionization electrode at that time as values to be applied to this analysis (step 40).

In the above example shown in the flowcharts of Figures 3 to 6, in steps 12, 22, 32, or 42, it is determined whether the ionization of the sample molecules has become unstable based on the output signal (ion detection signal) from the ion detector 145. Alternatively, it may be determined whether the ionization of the sample molecules has become unstable based on the current (hereinafter referred to as the ionization electrode current) flowing through the ionization electrode provided in the ionization chamber 111, i.e., the metal capillary 123 or the discharge electrode 125 of the ESI probe 121. The schematic configuration of the ion source in such a case will be described with reference to Figures 7 to 9. In these figures, the same or corresponding components as those shown in Figure 1 are given reference numerals with the same last two digits, and the description will be omitted as appropriate. In addition, although some components are shown in Figures 7 to 9 for simplification, the omitted components have almost the same configuration as those in Figure 1.

The ion source in the mass spectrometer shown in FIG. 7 performs ionization by both ESI and APCI, similar to that shown in FIG. 1, but the metal capillary tube 223 and the discharge electrode 225 of the ESI probe 221 are connected to a single high-voltage power supply 281. That is, this high-voltage power supply 281 is connected to both the metal capillary tube 223 and the discharge electrode 225 by a power supply line 283 having a branch portion 284. In addition, the counter electrode 226 provided between the ionization chamber 211 and the first intermediate vacuum chamber (omitted in FIG. 7) is grounded, so that the high-voltage power supply 281 can apply a high voltage between the metal capillary tube 223 and the counter electrode 226 of the ESI probe 221, and between the discharge electrode 225 and the counter electrode 226. Furthermore, a current detection unit 282 is provided between the branch 284 of the power supply line 283 and the high voltage power supply 281 to detect the current flowing through the metal capillary tube 223 and the discharge electrode 225 (i.e., the current flowing through the electric circuit including the metal capillary tube 223, the discharge electrode 225, the high voltage power supply 281, and the counter 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 the ion detector (not shown) and data obtained by the current detection unit 282. The detection signal by the current detection unit 282 is converted into digital data by an 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 includes a judgment unit 271 as a functional block. The control unit 250 and data processing unit 270 in this configuration example are actually computers equipped with a CPU, memory, and large-capacity storage device, and the functions of the functional blocks are achieved by executing dedicated software pre-installed on the computer.

8 shows ionization by ESI only, and the ionization chamber 311 is provided with an ESI probe 321 similar to that described above, but no discharge electrode for APCI is provided. 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, and a high voltage is applied between the metal capillary tube 323 of the ESI probe 321 and the counter electrode 326 by the high-voltage power supply 381. Furthermore, a current detection unit 382 is provided on the power supply line 383 between the metal capillary tube 323 and the high-voltage power supply 381 to detect the current flowing through the metal capillary tube 323 (i.e., the current flowing through the electric circuit including the metal capillary tube 323, the high-voltage power supply 381, and the counter electrode 326). Further, in this example, instead of blowing the heated dry gas toward the nebulized flow from the dry gas nozzle 327 provided in the counter electrode 326 as in the configuration shown in Fig. 1, the heated dry gas is blown toward the nebulized flow from a gas port 392 provided near the ESI probe 321. The gas port 392 includes a gas supply pipe 393 and a gas port heater 394 (corresponding to the heating section in the present invention) which is a cylindrical heater surrounding the gas supply pipe 393. The tip of the gas supply pipe 393 is directed toward the space in front of the spray nozzle of the ESI probe 321, and the base 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. The other configurations are the same as those in Fig. 7.

9 shows ionization only by APCI, and the ionization chamber 411 is provided with a discharge electrode 425 for APCI, but the spray nozzle 421 for spraying the sample liquid does not have a metal capillary as described above. 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 a high voltage is applied between the discharge electrode 425 and the counter electrode 426 by the high-voltage power supply 481. Furthermore, a current detection unit 482 for detecting a current flowing through the discharge electrode 425 (i.e., a current flowing through an electric circuit including the discharge electrode 425, the high-voltage power supply 481, and the counter electrode 426) is provided on the power supply line 483 between the discharge electrode 425 and the high-voltage power supply 481. In addition, in the configuration of FIG. 9, instead of the block heater 128 shown in FIG. 1, a nozzle heater 495 (corresponding to the heating unit in the present invention) is provided, which is a heater that cylindrically surrounds the space in front of the spray nozzle 421's spray port. The sample liquid is sprayed from the outlet of the spray nozzle 421 into the space surrounded by the nozzle heater 495, which promotes evaporation of the solvent in the sample liquid. The other configuration is the same as in FIG.

In a mass spectrometer having any of the configurations shown in Figures 7 to 9, the judgment unit 271, 371, 471 monitors the current detected by the current detection unit 282, 382, 482 (hereinafter referred to as the "ionization electrode current") and determines whether the ionization of sample molecules in the ionization chamber 211, 311, 411 has become unstable based on the fluctuation range of the current.

The method for setting ionization parameters in the configurations of Figures 7 to 9 is substantially the same as the procedure shown in the flowcharts of Figures 3 to 6. However, in this case, "ion detection signal" in the flowcharts of Figures 3 to 6 and their explanations shall be read as "ionization electrode current". Also, in the case of a configuration that includes a gas port heater 394 as in Figure 8 or a nozzle heater 495 as in Figure 9 instead of the block heater 128, "block heater 128" in the explanation of the flowcharts of Figures 3 to 6 shall be read as "gas port heater 394" or "nozzle heater 495".

Furthermore, the method for setting ionization parameters for a mass spectrometer according to the present invention can also be applied to a mass spectrometer equipped with a current detection unit 282, 382, 482 as shown in Figures 7 to 9, but not having a determination unit 271, 371, 471. In this case, the display control unit 252, 352, 452 causes the display unit 262, 362, 462 to display a waveform showing the time change in the ionization electrode current, and the user determines whether the ionization of sample molecules in the ionization chamber 211, 311, 411 has become unstable based on the waveform.

Although specific examples of the form for implementing the present invention have been described above, the present invention is not limited to the above-described embodiments, and appropriate modifications are permitted within the scope of the spirit of the present invention. For example, various examples of the configuration of the ionization electrode and the configuration of the heating unit have been given above, but the combinations thereof are not limited to those exemplified in Figures 1-2 and 7-9, and any combination may be used.

In addition, in the above embodiment, the program for executing the ionization parameter setting method according to the present invention is pre-installed on the computer, but the program can also be provided by storing it on a computer-readable recording medium.

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

(Item 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 compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
A method for setting a heating temperature by the heating unit in a mass spectrometer comprising:
a heating temperature of the heating unit is set to a predetermined initial temperature, and a sample liquid having a constant composition is sprayed from the nozzle, while monitoring an output signal from the ion detector or a current flowing through the ionization electrode;
When the fluctuation range of the output signal or the current is equal to or greater than a predetermined threshold value, the heating temperature is set to a value lower than the initial temperature.

(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 compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass analysis of the sample liquid while 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 an output signal from the ion detector or a current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of the 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 value;
It has the following.

(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 compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass analysis of the sample liquid while 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 an output signal from the ion detector or a current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of the 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 value;
The present invention may also have the following structure.

According to the mass spectrometry method described in paragraph 1, or the mass spectrometry apparatus described in paragraphs 2 or 3, in a mass spectrometry apparatus equipped with an ion source (ionization section) that ionizes a sample by atmospheric pressure ionization, boiling of the sample liquid in the ion source can be prevented, thereby making it possible to obtain stable analysis results.

(4) A mass spectrometry method according to one embodiment,
an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
A method for setting ionization parameters in an ionization unit in a mass spectrometer comprising:
a heating temperature by the heating unit is set to a predetermined initial temperature, a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode, and a sample liquid having a constant composition is sprayed from the nozzle, while monitoring an output signal from the ion detector or a current flowing through the ionization electrode;
When the fluctuation range of the output signal or the current is equal to or greater than a predetermined threshold value,
determining whether the sample liquid is likely to be boiling based on at least one of the heating temperature, the flow rate of the sample liquid, and the ratio of the organic solvent 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;
If it is determined that the possibility is low, the absolute value of the voltage applied from the high voltage power supply to the ionization electrode may be set to a value smaller than the initial voltage.

(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 compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the sample liquid supply unit, the heating unit, the high-voltage power supply, the mass separator, and the ion detector to perform mass analysis of the sample liquid while setting the heating temperature by the heating unit to a predetermined initial temperature and applying a predetermined initial voltage from the high-voltage power supply to the ionization electrode;
a determination unit that performs a first determination to determine whether or not a fluctuation range of an output signal from the ion detector or a 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, and when it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, further performs a second determination to determine whether or not it is highly likely that the sample liquid is boiling 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;
a notification unit that notifies a user to set the heating temperature to a value lower than the initial temperature when it is determined that the possibility is high, and that notifies a user to set an absolute value of the voltage applied from the high voltage power supply to the ionization electrode to a value lower than the initial voltage when it is determined that the possibility is low;
The present invention may also have the following structure.

(Item 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 compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the sample liquid supply unit, the heating unit, the high-voltage power supply, the mass separator, and the ion detector to perform mass analysis of the sample liquid while setting the heating temperature by the heating unit to a predetermined initial temperature and applying a predetermined initial voltage from the high-voltage power supply to the ionization electrode;
a determination unit that performs a first determination to determine whether or not a fluctuation range of an output signal from the ion detector or a 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, and when it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, further performs a second determination to determine whether or not it is highly likely that the sample liquid is boiling 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;
a setting unit that sets the heating temperature to a value lower than the initial temperature when it is determined that the possibility is high, and sets an absolute value of the voltage applied from the high voltage power supply to the ionization electrode to a value lower than the initial voltage when it is determined that the possibility is low;
The present invention may also have the following structure.

According to the mass spectrometry method described in paragraph 4, or the mass spectrometry apparatus described in paragraph 5 or 6, in a mass spectrometry apparatus equipped with an ion source (ionization section) that ionizes a sample by atmospheric pressure ionization, boiling of the sample liquid in the ion source and occurrence of abnormal discharge can be prevented, thereby making it possible to obtain stable analysis results.

111...Ionization chamber 121...ESI probe 123...Metal capillary 125...Discharge electrode 126...Counter electrode 128...Block heater 131...ESI high voltage power supply 132...APCI high voltage power supply 144...Quadrupole mass filter 145...Ion detector 150...Control unit 151...Analysis control unit 152...Display control unit 153...Set value storage unit 161...Input unit 162...Display unit 170...Data processing unit 171...Determination unit 180...LC
191...Temperature control unit 421...Spray nozzle 282, 382, 482...Current detection unit 281, 381, 481...High voltage power supply 394...Gas port heater 495...Nozzle heater

Claims (6)

an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds in the sample liquid by atmospheric pressure ionization;
a dry gas blowing unit that blows dry gas toward the sprayed flow from the nozzle from a front or side in the direction of travel of the sprayed flow;
a heating unit that heats the dry gas supplied to the dry gas blowing unit ;
a mass separator that separates the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
A method for setting a heating temperature by the heating unit in a mass spectrometer comprising:
a heating temperature of the heating unit is set to a predetermined initial temperature, and a sample liquid having a constant composition is sprayed from the nozzle, while monitoring an output signal from the ion detector or a current flowing through the ionization electrode;
A mass spectrometry method comprising the steps of: setting the heating temperature 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 value. an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds in the sample liquid by atmospheric pressure ionization;
a dry gas blowing unit that blows dry gas toward the sprayed flow from the nozzle from a front or side in the direction of travel of the sprayed flow;
a heating unit that heats the dry gas supplied to the dry gas blowing unit ;
a mass separator that separates the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass analysis of the sample liquid while 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 an output signal from the ion detector or a current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of the 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 value;
A mass spectrometer having a an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds in the sample liquid by atmospheric pressure ionization;
a dry gas blowing unit that blows dry gas toward the sprayed flow from the nozzle from a front or side in the direction of travel of the sprayed flow;
a heating unit that heats the dry gas supplied to the dry gas blowing unit ;
a mass separator that separates the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the heating unit, the mass separator, and the ion detector to perform mass analysis of the sample liquid while 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 an output signal from the ion detector or a current flowing through the ionization electrode is equal to or greater than a predetermined threshold value during execution of the 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 value;
A mass spectrometer having a an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
A method for setting ionization parameters in an ionization unit in a mass spectrometer comprising:
a heating temperature by the heating unit is set to a predetermined initial temperature, a predetermined initial voltage is applied from the high voltage power supply to the ionization electrode, and a sample liquid having a constant composition is sprayed from the nozzle, while monitoring an output signal from the ion detector or a current flowing through the ionization electrode;
When the fluctuation range of the output signal or the current is equal to or greater than a predetermined threshold value,
determining whether the sample liquid is likely to be boiling based on at least one of the heating temperature, the flow rate of the sample liquid, and the ratio of the organic solvent 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 supply to the ionization electrode is set to a value smaller than the initial voltage. an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the sample liquid supply unit, the heating unit, the high-voltage power supply, the mass separator, and the ion detector to perform mass analysis of the sample liquid while setting the heating temperature by the heating unit to a predetermined initial temperature and applying a predetermined initial voltage from the high-voltage power supply to the ionization electrode;
a determination unit that performs a first determination to determine whether or not a fluctuation range of an output signal from the ion detector or a 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, and when it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, further performs a second determination to determine whether or not it is highly likely that the sample liquid is boiling 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;
a notification unit that notifies a user to set the heating temperature to a value lower than the initial temperature when it is determined that the possibility is high, and that notifies a user to set an absolute value of the voltage applied from the high voltage power supply to the ionization electrode to a value lower than the initial voltage when it is determined that the possibility is low;
A mass spectrometer having a an ionization unit having a nozzle for spraying a sample liquid and an ionization electrode, and ionizing compounds 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 the ions generated in the ionization unit according to m/z;
an ion detector for detecting the ions separated by the mass separator;
a control unit that controls the ionization unit, the sample liquid supply unit, the heating unit, the high-voltage power supply, the mass separator, and the ion detector to perform mass analysis of the sample liquid while setting the heating temperature by the heating unit to a predetermined initial temperature and applying a predetermined initial voltage from the high-voltage power supply to the ionization electrode;
a determination unit that performs a first determination to determine whether or not a fluctuation range of an output signal from the ion detector or a 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, and when it is determined in the first determination that the fluctuation range is equal to or greater than the threshold value, further performs a second determination to determine whether or not it is highly likely that the sample liquid is boiling 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;
a setting unit that sets the heating temperature to a value lower than the initial temperature when it is determined that the possibility is high, and sets an absolute value of the voltage applied from the high voltage power supply to the ionization electrode to a value lower than the initial voltage when it is determined that the possibility is low;
A mass spectrometer having a

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