Ionization device and ionization method

Abstract

To prevent the contamination of a heating gas feeding mechanism, in an ionization device to ionize components contained in a liquid sample by spraying gas from the heating gas feeding mechanism onto the liquid sample to promote desolvation, the liquid sample being sprayed from an ionization probe.SOLUTION: Provided is an ionization device which is disposed in an ionization chamber 11 separated from analysis chambers 12, 13, 14 by a partition wall provided with an ion introduction port 113. The ionization device includes: an ionization probe 111 spraying a liquid sample; a heating gas supply mechanism 112 which includes a gas supply source and a heating part for heating gas supplied from the gas supply source and which blows the gas passing through the heating part 1122 in a direction crossing a direction in which the liquid sample is sprayed from the ionization probe 111; and a control part 32 controlling the heating gas supply mechanism 112 so as to continue blowing the gas from the heating gas supply mechanism 112 regardless of operations by a user, while the liquid sample is introduced into the ionization probe 111.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a technique for ionizing a liquid sample. [Background technology]

[0002] A liquid chromatograph mass spectrometer is used to measure a target component contained in a liquid sample. In measuring a target component using a liquid chromatograph mass spectrometer, the liquid sample is introduced into a liquid chromatograph, and the target component is separated in a column of the liquid chromatograph, and then introduced into a mass spectrometer. In the mass spectrometer, the target component contained in the liquid sample is ionized by, for example, an electrospray ionization (ESI) source, and the generated ions are separated and detected according to their mass-to-charge ratio.

[0003] The ESI source includes a capillary through which a liquid sample flows, and an ESI probe having a nebulizer gas flow path provided on the outer periphery of the capillary. In the ESI probe, the liquid sample flowing in the capillary is charged and transported to the tip of the ESI probe, and the tip is sprayed with nebulizer gas to spray the liquid sample as charged droplets into the ionization chamber. The charged droplets sprayed into the ionization chamber are repeatedly broken down into fine droplets by a process in which the surface electric field increases with the evaporation of the solvent (desolvation), and the droplets are split by the repulsion of the charges, and are finally ionized. The ions generated in the ionization chamber are drawn into the mass spectrometry chamber from an ion introduction port provided in the partition between the ionization chamber and the mass spectrometry chamber due to the pressure difference between the ionization chamber, which is at approximately atmospheric pressure, and the mass spectrometry chamber, which is a vacuum chamber located behind the ionization chamber. Patent documents 1 and 2 describe an ionization device equipped with an ESI probe and a heated gas supply mechanism that blows heated gas onto the charged droplets sprayed from the ESI probe in order to promote desolvation during the ionization process. In such an ionization device, the user can set the timing of spraying the heated gas appropriately according to the characteristics of the liquid sample, thereby promoting desolvation of sample components that are difficult to ionize and improving ionization efficiency. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Pat. No. 5,412,208 [Patent Document 2] U.S. Patent No. 6,759,650 Summary of the Invention [Problem to be solved by the invention]

[0005] When the liquid sample is sprayed from the ESI probe, an airflow is generated in the ionization chamber. In the ionization devices described in the cited documents 1 and 2, the user can freely set the timing of spraying the liquid sample from the ESI probe and the timing of blowing the heated gas from the heated gas supply mechanism. However, in an ionization device configured to blow gas from a heated gas supply mechanism provided separately from the ESI probe in a direction intersecting the direction in which the charged droplets are sprayed from the ESI probe (the central axis of spraying the charged droplets from the ESI probe and the central axis of blowing the gas from the heated gas supply mechanism are different), if there is a time period during which the heated gas supply mechanism does not blow the heated gas while the liquid sample is sprayed from the ESI probe, the airflow generated in the ionization chamber causes some of the charged droplets of the liquid sample to enter the inside of the heated gas supply mechanism. As a result, there is a problem that the inside of the heated gas supply mechanism is contaminated. Here, the case where the liquid sample is ionized by the ESI method is explained as an example, but the same problem as above also occurs when ionizing by other ionization methods (such as the APCI method).

[0006] The problem that the present invention aims to solve is to prevent contamination of a heated gas supply mechanism in an ionization device that ionizes components contained in a liquid sample by spraying gas from a heated gas supply mechanism provided separately from the ionization probe onto the liquid sample sprayed from the ionization probe to promote desolvation. [Means for solving the problem]

[0007] The present invention, which has been made to solve the above problems, provides an ionization device that is disposed in an ionization chamber separated from an analysis chamber by a partition wall having an ion introduction port, the device comprising: an ionization probe for nebulizing a liquid sample; a heating gas supply mechanism having a gas supply source and a heating unit for heating the gas supplied from the gas supply source, and spraying the gas in a direction intersecting a direction in which the liquid sample is sprayed from the ionization probe; a control unit that controls the operation of the heating gas supply mechanism so as to continue spraying the gas from the heating gas supply mechanism regardless of whether or not a user operates the heating gas supply mechanism while the liquid sample is being sprayed from the ionization probe; Equipped with.

[0008] Another aspect of the present invention, which has been made to solve the above problems, is a method for ionizing a liquid sample in an ionization chamber separated from an analysis chamber by a partition wall having an ion introduction port, comprising the steps of: introducing the liquid sample into an ionization probe and nebulizing it; a step of continuously blowing the gas from a heated gas supply mechanism provided separately from the ionization probe in a direction intersecting a direction in which the liquid sample is sprayed from the ionization probe, regardless of whether or not a user operates the ionization probe; and Includes. Effect of the Invention

[0009] In the ionization device and ionization method according to the present invention, gas is sprayed from a heated gas supply mechanism provided separately from the ionization probe in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe. That is, the central axis along which the charged droplets are sprayed from the ionization probe and the central axis along which the gas is sprayed from the heated gas supply mechanism are different axes. Then, while the liquid sample is being sprayed from the ionization probe, the operation of the heated gas supply mechanism is controlled so that the gas is continuously sprayed from the heated gas supply mechanism regardless of whether or not a user operates the mechanism. That is, the spraying of gas by the heated gas supply mechanism is automatically started at the same time or before the start of spraying of the liquid sample, and the spraying of gas by the heated gas supply mechanism is continued until the end of spraying of the liquid sample at the same time or after the end of spraying of the liquid sample. Therefore, it is possible to prevent the liquid sample from entering the inside of the heated gas supply mechanism and being contaminated by the gas flow sprayed from the heated gas supply mechanism. [Brief description of the drawings]

[0010] [Figure 1] 1 is a diagram showing the configuration of a main portion of a liquid chromatograph mass spectrometer including an embodiment of an ionization device according to the present invention. [Diagram 2] 2A to 2C are diagrams illustrating the configuration of each part arranged in an ionization chamber according to the present embodiment. [Diagram 3] FIG. 2 is an enlarged view of the tip of the ESI probe of the ionization device of the present embodiment. [Figure 4] 2 is a flowchart of an embodiment of an ionization method according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of an ionization device according to the present invention will now be described with reference to the drawings. Fig. 1 is a schematic diagram of a liquid chromatograph mass spectrometer 100 equipped with an ionization device of this embodiment.

[0012] The liquid chromatograph mass spectrometer 100 of this embodiment is roughly comprised of a liquid chromatograph 2, a mass spectrometer 1, and a control / processing unit 3 that controls each of these components.

[0013] The mass spectrometer 1 includes an ionization chamber 11 that is at approximately atmospheric pressure, and a vacuum chamber whose interior is evacuated by a vacuum pump (not shown). The interior of the vacuum chamber is separated into a first intermediate vacuum chamber 12, a second intermediate vacuum chamber 13, and an analysis chamber 14, and is configured as a differential pumping system in which the degree of vacuum increases in this order. The ionization chamber 11 and the first intermediate vacuum chamber 12 communicate with each other through a desolvation tube 113 provided in a partition wall separating them. The first intermediate vacuum chamber 12 and the second intermediate vacuum chamber 13 communicate with each other through an opening at the top of a skimmer 122 provided in the partition wall separating them. The second intermediate vacuum chamber 13 and the analysis chamber 14 communicate with each other through an opening provided in the partition wall separating them.

[0014] The ionization chamber 11 is provided with an electrospray ionization (ESI) probe 111, a heating gas supply mechanism 112, and a drying gas supply mechanism 114. A liquid sample is introduced directly into the ESI probe 111, or a liquid sample after its components have been separated in a liquid chromatograph column.

[0015] The heated gas supply mechanism 112 includes a gas supply source 1121, a heater 1122 (corresponding to the heating section in the present invention), a heated gas supply probe 1123, and a temperature measurement section 1124 (see FIG. 2; only the heated gas supply probe 1123 is shown in FIG. 1). The heated gas supply probe 1123 is disposed at a position spaced a predetermined distance from the tip of the ESI probe 111 so as to spray a heated gas at a predetermined flow rate (e.g., 1.0 to 30.0 L / min) onto the charged droplets sprayed from the ESI probe 111. This flow rate is adjusted, for example, by a flow rate adjustment section provided in the gas supply source 1121. For example, dry air or nitrogen gas is used as the heated gas. The supply of electricity to the heater 1122 is controlled by a measurement control section 33 (described later). It is also possible to pass the gas without supplying electricity to the heater 1122. For example, if the target component is easily decomposed or denatured by heat, gas at room temperature is sprayed without energizing the heater 1122. When energizing the heater 1122 to heat the gas, the measurement control unit 33 performs feedback control so that the temperature of the gas measured by the temperature measurement unit 1124 approaches a target temperature (e.g., 400°C).

[0016] The dry gas supply mechanism 114 includes a gas supply source 1141, a heating block 1142, and a dry gas supply pipe 1143 (see FIG. 2; only the heating block 1142 and the dry gas supply pipe 1143 are shown in FIG. 1). The dry gas supply pipe 1143 is arranged coaxially with the desolvation pipe 113 so as to surround the desolvation pipe 113, and is configured to blow dry gas against the ion flow flowing into the desolvation pipe 113. The flow rate of the dry gas is also adjusted, for example, by a flow rate adjustment unit provided in the gas supply source 1141. As the dry gas, for example, dry air or nitrogen gas is used. In this embodiment, the gas supply source 1121 and the gas supply source 1141 are provided separately, but gas may be supplied to each of the heating gas supply mechanism 112 and the dry gas supply mechanism 114 by providing a branch flow path from one gas supply source, for example.

[0017] 3, the ESI probe 111 includes a capillary 1111 through which a liquid sample flows, a nebulizer gas flow passage 1112 provided outside the capillary 1111, and a nebulizer gas supply mechanism 1113 that supplies nebulizer gas to the nebulizer gas flow passage 1112. In the ESI probe 111, the liquid sample flowing through the capillary 1111 is charged with a predetermined voltage (ESI voltage, typically a positive or negative voltage of an appropriate magnitude of 5.0 kV or less) and transported to the tip of the ESI probe 111, and the liquid sample is sprayed into the ionization chamber 11 as charged droplets by spraying a nebulizer gas (e.g., nitrogen gas) at the tip at a predetermined flow rate (e.g., 0.5 to 5.0 L / min). This flow rate is adjusted, for example, by a flow rate adjustment unit provided in the gas supply source 1121.

[0018] The charged droplets sprayed into the ionization chamber 11 are repeatedly broken down into fine particles by the increase in the surface electric field as the solvent evaporates (desolvation), and the repulsion between the charges causes the droplets to split, and finally the droplets are ionized. In addition, the desolvation of the charged droplets is promoted by blowing heated gas from the heated gas supply probe 1123 onto the charged droplets.

[0019] The ions generated in the ionization chamber 11 are drawn into the first intermediate vacuum chamber 12 from the desolvation tube 113 due to the pressure difference in the first intermediate vacuum chamber 12 located behind the desolvation tube 113. A dry gas supply tube 1143 is provided around the desolvation tube 113, and a dry gas is supplied to the dry gas supply tube 1143 from a gas supply source 1141 and heated by a heating block 1142 constituting a part of the partition wall. The dry gas supplied from the dry gas supply tube 1143 is blown against the ion flow flowing into the desolvation tube 113 from a direction opposite to the ion flow, thereby promoting desolvation of the ion flow. The desolvation tube 113 is also heated to a predetermined temperature (e.g., 300° C.) by the heating block 1142, and desolvation is promoted even while passing through the desolvation tube 113. The heating block 1142 is heated by a heating unit (e.g., energization of a heater) not shown.

[0020] An ion guide 121 composed of a plurality of rod-shaped electrodes is disposed in the first intermediate vacuum chamber 12. Ions introduced through the desolvation tube 113 are converged by the ion guide 121 to the vicinity of the ion optical axis (the central axis in the flight direction of the ions) C, and enter the second intermediate vacuum chamber 13 through an opening at the top of the skimmer 122.

[0021] An ion guide 131 composed of multiple rod-shaped electrodes is disposed in the second intermediate vacuum chamber 13. Ions introduced through an opening at the top of the skimmer 122 are converged near the ion optical axis C by the ion guide 131 and enter the analysis chamber 14 through an opening provided in a partition wall separating the second intermediate vacuum chamber 13 and the analysis chamber 14.

[0022] The analysis chamber 14 is provided with a front quadrupole mass filter 141, a collision cell 142, a rear quadrupole mass filter 144, and an ion detector 145. Each of the front quadrupole mass filter 141 and the rear quadrupole mass filter 144 is composed of a main rod, a pre-rod located in front of the main rod, and a post rod located in the rear of the main rod. The collision cell 142 is provided with a multipole rod electrode 143 that focuses ions in the collision cell 142 in the vicinity of the ion optical axis C. The collision cell 142 is also provided with a CID gas inlet that introduces an inert gas such as nitrogen gas as a collision induced dissociation (CID) gas.

[0023] Of the ions that have entered the analysis chamber 14, ions having a predetermined mass-to-charge ratio are selected as precursor ions by the front-stage quadrupole mass filter 141 and enter the collision cell 142. Inside the collision cell 142, the precursor ions are fragmented by collision with the CID gas to generate product ions. The ions generated in the collision cell 142 are mass-separated by the rear-stage quadrupole mass filter 144 and detected by the ion detector 145. An output signal from the ion detector 145 is transmitted to the control and processing unit 3 and stored in a memory unit 31 (described later).

[0024] The control / processing unit 3 includes a storage unit 31. A compound database (compound DB) 311 that stores information such as measurement conditions and analysis parameters of various compounds is stored in the storage unit 31. In this embodiment, the compound database 311 also stores information on the operation parameters (temperature, flow rate, etc. of the heating gas) of the heating gas supply mechanism 112 used when measuring each compound.

[0025] The control / processing unit 3 further includes, as functional blocks, a measurement condition setting unit 32, a measurement control unit 33 (corresponding to the control unit in the present invention), and a heating gas supply mechanism operation setting unit 34. The actual substance of the control / processing unit 3 is a general computer, and these functional blocks are realized by executing dedicated software preinstalled in the processor. An input unit 4 consisting of a mouse, keyboard, etc., and a display unit 5 consisting of a liquid crystal display, etc. are connected to the control / processing unit 3.

[0026] The heated gas supply mechanism operation setting unit 34 sets whether or not to set a measurement condition that stops the gas spraying operation from the heated gas supply mechanism 112 during the time period when the liquid sample or mobile phase is being sprayed from the ESI probe 111. The heated gas supply mechanism operation setting unit 34 is accessible only by predetermined persons (for example, only when a specific person such as an apparatus administrator logs in with a predetermined ID and password), and cannot be accessed by general users such as analysis operators. In this embodiment, except for exceptional cases where the predetermined person changes the settings of the heated gas supply mechanism operation setting unit 34, the setting of a measurement condition that stops the gas spraying operation from the heated gas supply mechanism 112 while the liquid sample is being sprayed is not accepted.

[0027] The mass spectrometer 1 of this embodiment is characterized by the arrangement and operation of the heating gas supply mechanism 112 in the ionization chamber 11. The configuration of the ionization chamber 11 will be described below. FIG. 2 is an enlarged view of the vicinity of the ionization chamber 11 of the mass spectrometer 1.

[0028] The ESI probe 111 is arranged so that its spray axis (the central axis of the traveling direction of the charged droplets sprayed from the ESI probe 111) and the central axis of the desolvation tube 113 are perpendicular to each other at the intersection X. In the present embodiment, as the most preferred embodiment, the spray axis of the ESI probe 111 is configured to be vertical, and the central axis of the desolvation tube 113 is configured to be horizontal. In addition, the heated gas supply probe 1123 is arranged so that the angle θ between the spray direction of the heated gas supply probe 1123 (the central axis of the traveling direction of the heated gas) and the spray axis of the ESI probe 111 is 60 degrees or more and 80 degrees or less. The range of the angle θ is based on the results of the study conducted by the applicant in the previous application (PCT / JP2021 / 030953). By setting the angle θ to 60 degrees or more, the tip of the ESI probe 111 and the heated gas supply probe 1123 do not physically interfere with each other, and the arrangement of both is facilitated. Furthermore, by setting the angle θ to 80 degrees or less, it is possible to reduce the possibility that the heated gas will be sprayed onto the tip of the ESI probe 111 and the liquid sample will boil within the ESI probe 111. The desolvation tube 113, which is a capillary provided in the partition between the ionization chamber 11 and the first intermediate vacuum chamber 12, is heated to a predetermined temperature by a heating block 1142 which constitutes a part of the partition.

[0029] The heating gas supply probe 1123 and the heating block 1142 are arranged so that the upper part of the heating block 1142 (the part located above the desolvation tube 113) is located on the central axis of the gas blowing direction from the heating gas supply probe 1123. That is, the heating gas supplied from the heating gas supply probe 1123 is blown onto the charged droplets at a position between the tip of the ESI probe 111 and the intersection X of the spray axis of the ESI probe 111 and the central axis of the desolvation tube 113 (a position of a distance L from the tip of the ESI probe 111). This distance L is set, for example, to 2.5 mm or more and 10 mm or less. The range of the distance L is also based on the results of the study conducted by the applicant in the previous application (PCT / JP2021 / 030953). By setting the distance L to 2.5 mm or more, the possibility of the tip of the ESI probe 111 and the tip of the heating gas supply probe 1123 coming close to each other and causing a discharge can be reduced. Furthermore, by setting the distance L to 10 mm or less, in a commonly used ionization device in which the difference in height between the tip of the ESI probe 111 and the central axis of the desolvation tube 113 is 10.5 mm, it is possible to blow heated gas onto the charged droplets at a position above the central axis of the desolvation tube 113, thereby promoting desolvation and improving the measurement sensitivity of ions.

[0030] In this embodiment, heated gas is sprayed onto the charged droplets sprayed from the tip of the ESI probe 111 before they reach the desolvation tube 113, so that the charged droplets are prevented from entering the analysis chamber 14 (first intermediate vacuum chamber 12, second intermediate vacuum chamber 13, and analysis chamber 14) in the form of droplets from the desolvation tube 113. Furthermore, supplying heated gas to such a position also prevents things other than ions generated from the liquid sample (undesired neutral molecules and ions present in the ionization chamber 11) from entering the analysis chamber 14 through the desolvation tube 113. This prevents contamination of each chamber on the analysis chamber side, improving the robustness of the mass spectrometer 1.

[0031] Next, an example of measurement of a liquid sample using the liquid chromatograph mass spectrometer 100 of this embodiment will be described with reference to the flow chart of FIG.

[0032] When the user issues an instruction to measure a liquid sample, the measurement condition setting unit 32 displays a list of compounds stored in the compound database 311 on the screen of the display unit 5. When the user selects a compound to be measured (target component) from the displayed list, the measurement condition setting unit 32 reads out the measurement conditions and analysis parameters of the compound and the operating parameters of the heated gas supply mechanism 112 from the compound database 311, and displays them on the screen of the display unit 5. The user makes changes to the measurement conditions, etc. as necessary, and then determines the measurement conditions, etc. (Step 1). When the measurement conditions, etc. are determined by the user, the measurement condition setting unit 32 creates a batch file for executing the measurement and analysis of the sample, and stores it in the memory unit 31.

[0033] As described above, the measurement conditions set by the user include the operation parameters of the heated gas supply mechanism 112. However, unless an exceptional setting is made in the heated gas supply mechanism operation setting unit 34 that allows the setting of a measurement condition that stops the gas spraying operation from the heated gas supply mechanism 112 during a time period when the liquid sample or mobile phase is sprayed from the ESI probe 111, it is not possible to set a measurement condition that stops the gas spraying operation during a time period when the liquid sample or mobile phase is sprayed from the ESI probe 111. Alternatively, when the user sets a measurement condition that stops the gas spraying operation during a time period when the liquid sample or mobile phase is sprayed from the ESI probe 111, the measurement condition setting unit 32 may automatically apply the operation parameters (temperature, flow rate, etc. of the heated gas) of the immediately preceding time period regardless of the setting, and overwrite the measurement condition setting.

[0034] After the batch file has been created, when the user issues a command to start measurement, the measurement control unit 33 executes the batch file and controls the operation of each part of the liquid chromatograph mass spectrometer 100 to measure the target component contained in the liquid sample.

[0035] At the start of the measurement, first, the first intermediate vacuum chamber 12, the second intermediate vacuum chamber 13, and the analysis chamber 14 in the vacuum chamber are evacuated to a predetermined vacuum level. In addition, the heater 1122 of the heating gas supply mechanism 112 is energized, and gas is supplied from the gas supply source 1121 at a predetermined flow rate (e.g., 5 L / min) (step 2). After energization of the heater 1122 is started, the temperature of the gas passing through the heater 1122 is measured by the temperature measurement unit 1124, and the amount of power supplied to the heater 1122 is adjusted so that the temperature is stabilized at a predetermined temperature (e.g., 400°C). The gas heated by the heater 1122 is sprayed into the ionization chamber 11. Furthermore, the dry gas supply mechanism 114 also supplies gas (dry gas) from the gas supply source 1141, and the gas is sprayed into the ionization chamber 11 from the dry gas supply pipe 1143 (step 3). By starting the spraying of the heated gas simultaneously with or before the spraying of the dry gas, undesired substances present in the ionization chamber 11 are prevented from entering the interior of the heated gas supply mechanism 112 due to the airflow generated by the spraying of the dry gas.

[0036] When each chamber in the vacuum chamber is evacuated to a predetermined vacuum level and the gas in the heated gas supply mechanism 112 reaches a predetermined temperature, the measurement control unit 33 injects the liquid sample that has been set in advance in the liquid chromatograph 2 (or an autosampler connected to the liquid chromatograph 2) from the injector. The liquid sample introduced into the liquid chromatograph 2 is carried along by the flow of the mobile phase and introduced into the column, where each component is separated.

[0037] Various components in the liquid sample separated in the column of the liquid chromatograph 2 are sequentially introduced into the ESI probe 111 together with the mobile phase (step 4), and are sprayed into the ionization chamber 11 as charged droplets (step 5). Heated gas is blown onto the charged droplets from the heated gas supply probe 1123 (step 6), thereby promoting desolvation. The ion flow generated from the charged droplets is drawn into the first intermediate vacuum chamber 12 through the desolvation tube 113 due to the pressure difference between the ionization chamber 11 and the first intermediate vacuum chamber 12. At this time, a dry gas flow is blown from the dry gas supply tube 1143 in the opposite direction to the ion flow (step 7), and the ion flow passes through the heated desolvation tube 113, thereby further promoting desolvation.

[0038] When the measurement of the liquid sample is completed (step 8), the measurement control unit 33 stops the supply of the mobile phase in the liquid chromatograph 2. Then, the supply of gas from the gas supply source 1141 of the dry gas supply mechanism 114 is stopped (step 9). At the same time (or after the supply of gas from the gas supply source 1141 is stopped), the supply of gas from the gas supply source 1121 of the heated gas supply mechanism 112 is stopped (step 10). By stopping the blowing of the heated gas at the same time as or after the blowing of the dry gas, undesired substances present in the ionization chamber 11 are prevented from entering the inside of the heated gas supply mechanism 112 due to the airflow generated by the blowing of the dry gas.

[0039] In this way, in the liquid chromatograph mass spectrometer 100 of this embodiment, the supply of heated gas from the heated gas supply probe 1123 begins before the mobile phase or liquid sample is introduced from the liquid chromatograph 2 into the ESI probe 111, and the heated gas continues to be supplied at all times while the mobile phase or liquid sample is being introduced into the ESI probe 111.

[0040] When various components in the liquid sample are sprayed together with the mobile phase from the ESI probe 111, an airflow is generated in the ionization chamber 11. In addition, a dry gas is also sprayed from the dry gas supply mechanism 114 in a direction opposite to the ion flow. In an ionization device having a configuration in which gas is sprayed from the heated gas supply mechanism 112 provided separately from the ESI probe 111 in a direction intersecting the direction in which the charged droplets are sprayed toward the charged droplets sprayed from the ESI probe 111 as in this embodiment (the central axis for spraying the charged droplets from the ESI probe 111 and the central axis for spraying the gas from the heated gas supply mechanism 112 are different axes), if gas is not sprayed from the heated gas supply probe 1123, the components in the liquid sample and some of the charged droplets of the mobile phase may enter the inside of the heated gas supply mechanism 112 due to the airflow generated in the ionization chamber 11, thereby possibly contaminating the inside of the heated gas supply mechanism 112. Contamination occurs when components in the liquid sample that have entered the heating gas supply mechanism 112 during the previous measurement are sprayed together with the heating gas onto the liquid sample to be measured next. To prevent such contamination, the heating gas supply mechanism 112 must be cleaned after each measurement, which is time-consuming and laborious. In this embodiment, the measurement control unit 33 constantly sprays heating gas from the heating gas supply probe 1123 while the liquid sample is being introduced into the ESI probe 111, so that the components in the liquid sample and the mobile phase can be prevented from entering the heating gas supply mechanism 112 due to this gas flow.

[0041] In the above measurement example, the measurement control unit 33 operates the heated gas supply mechanism 112 in synchronization with the start and end of the measurement of the liquid sample, and the heated gas is sprayed from the heated gas supply probe 1123 to the ionization chamber before the liquid sample and the mobile phase are introduced into the ESI probe 111, but other operation modes can be adopted. For example, the supply of gas from the gas supply source 1121 of the heated gas supply mechanism 112 can be started and ended simultaneously with the start and end of the supply of nebulizer gas by the nebulizer gas supply mechanism 1113 in the ESI probe 111. The nebulizer gas is used to spray the liquid sample and the mobile phase introduced into the ESI probe 111 into the ionization chamber 11, so by spraying the gas from the heated gas supply probe 1123 in synchronization with this, it is possible to reliably prevent components in the liquid sample from entering the inside of the heated gas supply mechanism 112. That is, any method can be adopted as long as the gas can be continuously sprayed from the heated gas supply mechanism 112 at least while the liquid sample is being sprayed from the ESI probe 111.

[0042] In the above measurement example, only one liquid sample was measured, but multiple liquid samples may be set in the autosampler and measured in sequence. In such a measurement, a waiting time may be provided between the measurements of liquid samples. For example, when performing gradient analysis with the liquid chromatograph 2, after starting the measurement of one liquid sample, the mobile phase is equilibrated with the liquid chromatograph 2. In this way, if there is a time period (waiting time period) between the measurements of liquid samples during which the liquid sample or the like is not introduced into the ESI probe 111, the blowing of the heated gas from the heated gas supply probe 1123 to the ionization chamber 11 may be temporarily stopped, or the flow rate of the heated gas may be reduced from the measurement flow rate to the standby flow rate (measurement flow rate > standby flow rate). Of course, the same flow rate of gas may be blown from the heated gas supply probe 1123 to the ionization chamber 11 during both the measurement time period and the standby time period.

[0043] In the above measurement example, in the heated gas supply mechanism 112, the gas supplied from the gas supply source 1121 is heated to a predetermined temperature by the heater 1122 and sprayed from the heated gas supply probe 1123 to the ionization chamber 11, but the heater 1122 may not be energized and the gas supplied from the gas supply source 1121 may be sprayed to the ionization chamber 11 without being heated. For example, when the target component is easily decomposed or denatured by heat, it is preferable to spray unheated gas. When measuring such a target component, it is preferable to not energize the heating block 1142, but to spray unheated dry gas onto the ion flow and introduce the ion flow into an unheated desolvation tube.

[0044] In the above measurement example, the dry gas supply mechanism 114 is used, but the dry gas supply mechanism 114 may not be used (or the dry gas supply mechanism 114 may be provided but not operated for measurement). In that case, an air current that pushes the ion flow back into the ionization chamber 11 is less likely to occur than when a dry gas is blown. Therefore, when performing measurement without blowing a dry gas to the ion flow, the flow rate of the gas blown from the heated gas supply probe 1123 to the ionization chamber 11 may be reduced compared to when a dry gas is blown to the ion flow. For example, the measurement control unit 33 may blow gas from the heated gas supply mechanism 112 at a predetermined first flow rate when gas is being blown from the dry gas supply mechanism 114, and blow gas from the heated gas supply mechanism 112 at a second flow rate lower than the first flow rate when gas is not being blown from the dry gas supply mechanism 114.

[0045] The above-described embodiment and measurement examples are merely examples and can be modified as appropriate in accordance with the spirit of the present invention.

[0046] In the above embodiment, the user is required to set the measurement conditions including the operation parameters (temperature, flow rate, etc. of the heating gas) of the heating gas supply mechanism 112, but the user may not be required to set the operation parameters of the heating gas supply mechanism 112. In that case, for example, the measurement condition setting unit 32 may be configured to automatically set the measurement conditions such that the heating gas supply mechanism 112 is operated with predetermined operation parameters according to the time period during which the liquid sample or mobile phase is sprayed from the ESI probe 111, which is determined by the measurement conditions set by the user. In addition, in the above embodiment, the heating gas supply mechanism operation setting unit 34 is provided, but this is also optional. The essential requirement in the above embodiment is that the heating gas supply mechanism 112 continues to spray gas (heated gas or non-heated gas) regardless of whether or not the user operates the device while the liquid sample or mobile phase is sprayed from the ESI probe 111, and any appropriate configuration may be adopted as long as this requirement is satisfied.

[0047] Although the liquid chromatograph mass spectrometer 100 is used, the same configuration as above can also be used in a mass spectrometer that does not include a liquid chromatograph and in which a liquid sample is directly introduced into an ESI probe. In that case, gas should be continuously sprayed from the heated gas supply probe 1123 into the ionization chamber while the liquid sample is being sprayed from the ESI probe.

[0048] In the above embodiment, the ionization device (ESI source) has the ionization chamber 11 equipped with the ESI probe 111. However, the same configuration as above can be adopted in an ionization device (APCI source) equipped with an ionization probe for spraying a liquid sample and a corona needle for atmospheric pressure chemical ionization (APCI) instead of the ESI probe 111. Alternatively, the same configuration as above can be adopted in an ionization device equipped with an ESI probe and a corona needle for APCI (so-called dual ionization device). In the above embodiment, the ESI probe 111 and the desolvation tube 113 are arranged so that the direction of spraying a liquid sample from the ESI probe 111 and the central axis of the desolvation tube 113 are perpendicular to each other (orthogonal arrangement), but this is a preferred embodiment, and the present invention can be applied to other arrangements as well. Furthermore, the heated gas supply mechanism is provided separately from the ionization probe, and can be configured to spray gas in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe (the central axis along which charged droplets are sprayed from the ionization probe and the central axis along which gas is sprayed from the heated gas supply mechanism are separate axes), and any appropriate arrangement other than the preferred embodiment shown in the above can be adopted.

[0049] In the above embodiment, the generated ions are subjected to mass analysis, but the same ionization device as in the above embodiment can be used in devices for other measurements such as ion mobility measurement, etc. Furthermore, when performing mass analysis, mass analysis units of various configurations (single quadrupole type, ion trap type, time-of-flight type, etc.) other than the triple quadrupole type of the above embodiment can be used.

[0050] [Aspects] It will be apparent to those skilled in the art that the above-described exemplary embodiments are illustrative of the following aspects.

[0051] (Section 1) One aspect of the present invention is an ionization device disposed in an ionization chamber separated from an analysis chamber by a partition wall having an ion introduction port, an ionization probe for nebulizing a liquid sample; a heating gas supply mechanism having a gas supply source and a heating unit for heating the gas supplied from the gas supply source, and spraying the gas in a direction intersecting a direction in which the liquid sample is sprayed from the ionization probe; a control unit that controls the operation of the heating gas supply mechanism so as to continue spraying the gas from the heating gas supply mechanism regardless of whether or not a user operates the heating gas supply mechanism while the liquid sample is being sprayed from the ionization probe; Equipped with. (Section 7) Another aspect of the present invention is a method for ionizing a liquid sample in an ionization chamber separated from an analysis chamber by a partition wall having an ion introduction port, the method comprising the steps of: introducing the liquid sample into an ionization probe and nebulizing it; a step of continuously blowing the gas from a heated gas supply mechanism provided separately from the ionization probe in a direction intersecting a direction in which the liquid sample is sprayed from the ionization probe, regardless of whether or not a user operates the ionization probe; and Includes.

[0052] When the liquid sample is sprayed from the ionization probe in the ionization chamber, an air flow is generated in the ionization chamber. In conventional ionization devices, the user can set the timing of spraying the liquid sample from the ESI probe and the timing of blowing the heated gas from the heated gas supply mechanism as appropriate, but in an ionization device configured to blow gas from a heated gas supply mechanism provided separately from the ESI probe to the charged droplets sprayed from the ESI probe in a direction intersecting the direction in which the charged droplets are sprayed (the central axis for spraying the charged droplets from the ESI probe and the central axis for blowing the gas from the heated gas supply mechanism are different axes), if the heated gas supply mechanism does not blow gas while the liquid sample is being sprayed from the ionization probe, the air flow generated in the ionization chamber will cause some of the charged droplets of the liquid sample to enter the inside of the heated gas supply mechanism, thereby contaminating the inside of the heated gas supply mechanism. If the liquid sample that entered the inside of the heated gas supply mechanism during the previous measurement is blown together with the gas onto the liquid sample for the next measurement, contamination will occur. Furthermore, in order to prevent such contamination, the heating gas supply mechanism must be cleaned after each measurement, which is time-consuming and laborious.

[0053] In the ionization device according to paragraph 1 and the ionization method according to paragraph 7, the operation of the ionization probe and the heated gas supply mechanism is controlled so that the heated gas supply mechanism continues to spray gas while the liquid sample is being sprayed from the ionization probe, regardless of whether or not a user operates the ionization probe. In other words, the heated gas supply mechanism automatically starts spraying gas at the same time as or before the start of spraying the liquid sample, and continues spraying gas until the liquid sample has ended at the same time as or after the end of spraying. This makes it possible to prevent the liquid sample from entering the heated gas supply mechanism due to the gas flow sprayed out from the heated gas supply mechanism.

[0054] (Section 2) The ionization device according to paragraph 2 is the ionization device according to paragraph 1. The heated gas supply mechanism is capable of performing a heating operation in which the gas supplied from the gas supply source is heated by the heating unit and sprayed, and a non-heating operation in which the gas supplied from the gas supply source is sprayed without being heated by the heating unit.

[0055] In the ionization device according to paragraph 2, even if the target component to be measured is easily decomposed or denatured by heat, the heated gas supply mechanism can be operated in a non-heated manner to prevent the liquid sample from entering the inside of the heated gas supply mechanism and causing contamination, and also promotes desolvation of the charged droplets.

[0056] (Section 3) The ionization device according to paragraph 3 is an ionization device according to paragraph 1 or 2, the ionization probe includes a nebulizer gas supply mechanism for supplying a nebulizer gas for nebulizing the liquid sample; The control unit controls the operation of the heating gas supply mechanism in synchronization with the operation of the nebulizer gas supply mechanism.

[0057] In the ionization device of paragraph 3, the heating gas supply mechanism is operated to continue spraying gas in synchronization with the operation of the nebulizer gas mechanism that supplies nebulizer gas for nebulizing the liquid sample in the ESI probe, and while the liquid sample is being nebulized by the nebulizer gas, it is possible to reliably prevent the nebulized liquid sample from entering the inside of the heating gas supply mechanism and becoming contaminated.

[0058] (Section 4) The ionization device according to paragraph 4 is an ionization device according to any one of paragraphs 1 to 3, The control unit sprays the gas from the heated gas supply mechanism at a predetermined measurement flow rate during a measurement time period when measurement of the liquid sample is being performed, and sprays the gas from the heated gas supply mechanism at a standby flow rate lower than the measurement flow rate during a standby time period when measurement of the liquid sample is not being performed.

[0059] In the ionization device according to paragraph 4, the amount of gas used can be reduced by reducing the flow rate of gas sprayed from the heated gas supply mechanism during standby periods when no liquid sample measurements are being performed. Note that if nothing is sprayed from the ESI probe during standby periods when no liquid sample measurements are being performed, or if the liquid sprayed from the ESI probe does not contaminate the heated gas supply mechanism, the standby flow rate may be set to zero (i.e., gas spraying may be stopped).

[0060] (Section 5) The ionization device according to paragraph 5 is an ionization device according to any one of paragraphs 1 to 4, further comprising: A dry gas supply mechanism that blows gas in a direction opposite to the ion flow entering the ion inlet. Equipped with.

[0061] In the ionization device according to the fifth aspect, the desolvation of the ion flow introduced into the ion introduction port can be further promoted by blowing a dry gas thereon.

[0062] (Section 6) The ionization device according to paragraph 6 is an ionization device according to paragraph 5, The control unit blows the gas from the heated gas supply mechanism at a predetermined first flow rate when the gas is being blown from the dry gas supply mechanism, and blows the gas from the heated gas supply mechanism at a second flow rate lower than the first flow rate when the gas is not being blown from the dry gas supply mechanism.

[0063] In the ionization device according to paragraph 6, when gas is not being blown from the drying gas supply mechanism, the charged droplets of the liquid sample are less likely to enter the inside of the heating gas supply mechanism than when gas is being blown. By reducing the flow rate of the gas blown from the heating gas supply mechanism when gas is not being blown from the drying gas supply mechanism, the amount of gas used can be reduced. [Explanation of symbols]

[0064] 100...Liquid chromatograph mass spectrometer 1...Mass spectrometer 11…Ionization chamber 111…ESI probe 1111…Capillary 1112...Nebulizer gas flow path 1113...Nebulizer gas supply mechanism 112...Heating gas supply mechanism 1121…Gas supply source 1122…Heater 1123…Heated gas supply probe 1124...Temperature measurement section 113... Desolvation tube 114...Drying gas supply mechanism 1141…Gas supply source 1142…Heating block 1143...Dry gas supply pipe 12…First intermediate vacuum chamber 121…Ion Guide 122…Skimmer 13…Second intermediate vacuum chamber 131…Ion Guide 14…Analysis room 141...Pre-quadrupole mass filter 142…Collision cell 143...Multipole rod electrode 144...Post-quadrupole mass filter 145…Ion detector 2. Liquid chromatograph 3. Control and processing section 31...Storage section 311...Compound database 32…Measurement condition setting section 33...Measurement control section 34...Heating gas supply mechanism operation setting unit 4. Input section 5...Display section C…Ion optical axis X: Intersection of the spray axis of the ESI probe and the central axis of the ion inlet L: Distance from the tip of the ESI probe to the intersection of the spray axis of the ESI probe and the spray direction of the heated gas supply probe θ: Angle between the spray axis of the ESI probe and the spray direction of the heated gas supply probe

Claims

1. An ionization device disposed in an ionization chamber separated from an analysis chamber by a partition wall having an ion introduction port, an ionization probe for nebulizing a liquid sample; a heating gas supply mechanism having a gas supply source and a heating unit for heating the gas supplied from the gas supply source, and spraying the gas in a direction intersecting a direction in which the liquid sample is sprayed from the ionization probe; a control unit that controls the operation of the heating gas supply mechanism so as to continue spraying the gas from the heating gas supply mechanism regardless of whether or not a user operates the heating gas supply mechanism while the liquid sample is being sprayed from the ionization probe; An ionization device comprising:

2. 2. The ionization device according to claim 1, wherein the heated gas supply mechanism is capable of performing a heating operation in which the gas supplied from the gas supply source is heated by the heating unit and sprayed, and a non-heating operation in which the gas supplied from the gas supply source is sprayed without being heated by the heating unit.

3. the ionization probe includes a nebulizer gas supply mechanism for supplying a nebulizer gas for nebulizing the liquid sample; The ionization device according to claim 1 , wherein the control unit controls an operation of the heating gas supply mechanism in synchronization with an operation of the nebulizer gas supply mechanism.

4. The ionization device of claim 1, wherein the control unit sprays the gas from the heating gas supply mechanism at a predetermined measurement flow rate during a measurement period when measurement of the liquid sample is being performed, and sprays the gas from the heating gas supply mechanism at a standby flow rate lower than the measurement flow rate during a standby period when measurement of the liquid sample is not being performed.

5. moreover, A dry gas supply mechanism that blows gas in a direction opposite to the ion flow entering the ion inlet. The ionization device of claim 1 , comprising:

6. 6. The ionization device of claim 5, wherein the control unit blows the gas from the heating gas supply mechanism at a predetermined first flow rate when the gas is being blown from the drying gas supply mechanism, and blows the gas from the heating gas supply mechanism at a second flow rate lower than the first flow rate when the gas is not being blown from the drying gas supply mechanism.

7. A method for ionizing a liquid sample in an ionization chamber separated from an analysis chamber by a partition wall having an ion introduction port, comprising: introducing the liquid sample into an ionization probe and nebulizing it; a step of continuously blowing the gas from a heated gas supply mechanism provided separately from the ionization probe in a direction intersecting a direction in which the liquid sample is sprayed from the ionization probe, regardless of whether or not a user operates the ionization probe; and The ionization method comprising:

Images