Ionization apparatus 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

[0003]

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

Background Art

[0002] In order to measure a target component contained in a liquid sample, a liquid chromatography mass spectrometer is used. In the measurement of the target component using a liquid chromatography mass spectrometer, a liquid sample is introduced into a liquid chromatograph, the target component is separated by a column of the liquid chromatograph, and then introduced into a mass spectrometer. In the mass spectrometer, for example, a target component contained in a liquid sample is ionized by an electrospray ionization (ESI) source, and the generated ions are separated and detected according to the 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 through the capillary is charged and transported to the tip of the ESI probe, and by spraying nebulizer gas at the tip, the liquid sample is sprayed into the ionization chamber as charged droplets. The charged droplets sprayed into the ionization chamber are repeatedly refined through a process in which the surface electric field increases as the solvent evaporates (desolvation) and the droplets split due to the repulsion between charges, and are finally ionized. The ions generated in the ionization chamber are drawn into the mass spectrometry chamber through an ion inlet provided in the partition wall 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 in the subsequent stage. Patent Documents 1 and 2 describe an ionization device provided with a heating gas supply mechanism for spraying a heating gas onto the charged droplets sprayed from the ESI probe in addition to the ESI probe in order to promote desolvation in such an ionization process. In such an ionization device, the user can promote the desolvation of a sample component that is difficult to ionize and increase the ionization efficiency by appropriately setting the timing of spraying the heating gas according to the characteristics of the liquid sample.

Prior Art Documents

[0004] [Patent Document 1] U.S. Patent No. 5412208 [Patent Document 2] U.S. Patent No. 6,759,650 [Overview of the project] [Problems that the invention aims to solve]

[0005] When a liquid sample is sprayed from the ESI probe, an airflow is generated in the ionization chamber. In the ionization apparatus described in References 1 and 2, the timing of spraying the liquid sample from the ESI probe and the timing of blowing heated gas from the heating gas supply mechanism can be freely set by the user. However, in an ionization apparatus configured such that the heated gas supply mechanism, which is provided separately from the ESI probe, blows gas onto the charged droplets sprayed from the ESI probe in a direction intersecting the direction in which the charged droplets are sprayed (the central axis from which the charged droplets are sprayed from the ESI probe and the central axis from which the gas is blown from the heating gas supply mechanism are on different axes), if there is a period of time when heated gas is not blown from the heating gas supply mechanism while the liquid sample is being sprayed from the ESI probe, some of the charged droplets of the liquid sample will enter the heating gas supply mechanism due to the airflow generated in the ionization chamber. As a result, there was a problem of contamination inside the heating gas supply mechanism. Here, we have explained using the case of ionizing a liquid sample by the ESI method as an example, but the same problem exists 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 the heating gas supply mechanism in an ionization apparatus that ionizes components contained in a liquid sample by blowing gas from a heating gas supply mechanism, which is 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, made to solve the above problems, is an ionization apparatus arranged in an ionization chamber separated from an analysis chamber by a partition wall provided with an ion inlet, An ionization probe that sprays a liquid sample, A heating gas supply mechanism comprising a gas supply source and a heating unit for heating the gas supplied from the gas supply source, wherein the gas is blown in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe, A control unit controls the operation of the heating gas supply mechanism so that the heating gas supply mechanism continues to blow the gas from the heating gas supply mechanism regardless of whether or not the user is operating it, while the liquid sample is being sprayed from the ionization probe. It is equipped with.

[0008] Another aspect of the present invention, 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 provided with an ion inlet, A step of introducing the liquid sample into the ionization probe and spraying it, The system includes a gas supply source and a heating unit for heating the gas supplied from the gas supply source, and a heating gas supply mechanism, provided separately from the ionization probe, continuously blows the gas in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe, regardless of whether or not the user is operating the system. Includes. [Effects of the Invention]

[0009] In the ionization apparatus and ionization method according to the present invention, a heating gas supply mechanism, provided separately from the ionization probe, blows gas in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe. That is, the central axis from which charged droplets are sprayed from the ionization probe and the central axis from which gas is blown from the heating gas supply mechanism are separate axes. The operation of the heating gas supply mechanism is controlled so that it continues to blow gas from the heating gas supply mechanism regardless of whether or not the user is operating it while the liquid sample is being sprayed from the ionization probe. In other words, the heating gas supply mechanism automatically starts blowing gas at the same time as or before the start of spraying the liquid sample and continues blowing gas from the heating gas supply mechanism until the same time as or after the end of spraying the liquid sample. Therefore, it is possible to prevent the liquid sample from entering the inside of the heating gas supply mechanism and contaminating it with the gas flow blown out from the heating gas supply mechanism. [Brief explanation of the drawing]

[0010] [Figure 1] A diagram showing the main components of a liquid chromatograph-mass spectrometer, including one embodiment of the ionization apparatus according to the present invention. [Figure 2] A diagram illustrating the configuration of each part arranged in the ionization chamber of this embodiment. [Figure 3] An enlarged view of the tip of the ESI probe of the ionization apparatus in this embodiment. [Figure 4] A flowchart of one embodiment of the ionization method according to the present invention. [Modes for carrying out the invention]

[0011] Embodiments of the ionization apparatus according to the present invention will be described below with reference to the drawings. Figure 1 is a schematic diagram of a liquid chromatograph-mass spectrometer 100 equipped with the ionization apparatus of this embodiment.

[0012] The liquid chromatograph-mass spectrometer 100 of this embodiment comprises, broadly speaking, a liquid chromatograph 2, a mass spectrometer 1, and a control / processing unit 3 that controls each of these parts.

[0013] The mass spectrometer 1 comprises an ionization chamber 11 at approximately atmospheric pressure and a vacuum chamber whose interior is evacuated by a vacuum pump (not shown). The inside of the vacuum chamber is divided into a first intermediate vacuum chamber 12, a second intermediate vacuum chamber 13, and an analysis chamber 14, and has a differential pumping system configuration in which the vacuum level increases in this order. The ionization chamber 11 and the first intermediate vacuum chamber 12 are connected by a desolvation tube 113 provided in the partition wall separating them. The first intermediate vacuum chamber 12 and the second intermediate vacuum chamber 13 are connected by 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 are connected by an opening provided in the partition wall separating them.

[0014] The ionization chamber 11 houses an electrospray ionization (ESI) probe 111, a heating gas supply mechanism 112, and a drying gas supply mechanism 114. The ESI probe 111 is either directly into the liquid sample or into the liquid sample after its components have been separated by a liquid chromatography column.

[0015] The heating gas supply mechanism 112 comprises a gas supply source 1121, a heater 1122 (corresponding to the heating section in this invention), a heating gas supply probe 1123, and a temperature measuring unit 1124 (see Figure 2; only the heating gas supply probe 1123 is shown in Figure 1). The heating gas supply probe 1123 is positioned at a predetermined distance from the tip of the ESI probe 111 and is configured to blow heating gas at a predetermined flow rate (e.g., 1.0 to 30.0 L / min) onto charged droplets sprayed from the ESI probe 111. This flow rate is adjusted, for example, by a flow rate adjustment unit provided in the gas supply source 1121. As the heating gas, for example, dry air or nitrogen gas can be used. The energization of the heater 1122 is controlled by the measurement control unit 33 (described later). It is also possible to pass the gas through without energizing the heater 1122. For example, if the target component is easily decomposed or denatured by heat, the heater 1122 is not energized, and room temperature gas is blown in. When the heater 1122 is energized to heat the gas, the measurement control unit 33 performs feedback control to bring the gas temperature measured by the temperature measurement unit 1124 closer to the target temperature (e.g., 400°C).

[0016] The drying gas supply mechanism 114 comprises a gas supply source 1141, a heating block 1142, and a drying gas supply pipe 1143 (see Figure 2; Figure 1 shows only the heating block 1142 and the drying gas supply pipe 1143). The drying 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 drying gas onto the ion flow flowing into the desolvation pipe 113. The flow rate of the drying gas is also adjusted, for example, by a flow rate adjustment unit provided in the gas supply source 1141. Dry gas can be used, for example, dry air or nitrogen gas. In this embodiment, gas supply sources 1121 and 1141 are provided separately, but gas may be supplied to both the heating gas supply mechanism 112 and the drying gas supply mechanism 114 by providing branched flow paths from a single gas supply source.

[0017] As shown in the partial enlarged view of the tip in FIG. 3, the ESI probe 111 includes a capillary 1111 through which a liquid sample flows, a nebulizer gas flow path 1112 provided outside the capillary 1111, and a nebulizer gas supply mechanism 1113 that supplies nebulizer gas to the nebulizer gas flow path 1112. In the ESI probe 111, the liquid sample flowing through the capillary 1111 is charged by 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. At the tip, a nebulizer gas (e.g., nitrogen gas) is sprayed at a predetermined flow rate (e.g., 0.5 to 5.0 L / min), thereby spraying the liquid sample into the ionization chamber 11 as charged droplets. 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 refined by repeating the process of increasing the surface electric field due to the evaporation (desolvation) of the solvent and splitting due to the repulsion between charges, and finally ionized. In addition, the desolvation of the charged droplets is promoted by spraying 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 in the subsequent stage. A drying gas supply tube 1143 is provided around the desolvation tube 113, and the drying gas supply tube 1143 is supplied with drying gas heated by a heating block 1142 that is supplied from the gas supply source 1141 and constitutes a part of the partition wall. The drying gas supplied from the drying gas supply tube 1143 is sprayed onto the ion flow flowing into the desolvation tube 113 from the direction opposite to the ion flow, thereby promoting the 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 this desolvation tube 113. The heating block 1142 is heated by a heating unit (such as energizing a heater) not shown.

[0020] An ion guide 121, composed of multiple rod-shaped electrodes, is placed in the first intermediate vacuum chamber 12. Ions introduced through the desolvation tube 113 are focused by the ion guide 121 near the ion optical axis (the central axis of the ion's flight direction) C, and enter the second intermediate vacuum chamber 13 through the opening at the top of the skimmer 122.

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

[0022] The analysis chamber 14 houses a pre-quadrupole mass filter 141, a collision cell 142, a post-quadrupole mass filter 144, and an ion detector 145. Both the pre-quadrupole mass filter 141 and the post-quadrupole mass filter 144 consist of a main rod, a pre-rod located in front of the main rod, and a post-rod located behind the main rod. The collision cell 142 is equipped with a multipole rod electrode 143 that focuses ions within the collision cell 142 near the ion optical axis C. The collision cell 142 is also provided with a CID gas introduction section for introducing an inert gas such as nitrogen gas as a collision-induced dissociation (CID) gas.

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

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

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

[0026] The heating gas supply mechanism operation setting unit 34 sets whether or not to allow the setting of measurement conditions that stop the gas blowing operation from the heating gas supply mechanism 112 during the time when a liquid sample or mobile phase is being sprayed from the ESI probe 111. The heating gas supply mechanism operation setting unit 34 is accessible only to predetermined persons (for example, only when a specific person such as the device administrator logs in with a predetermined ID and password), and is not accessible to general users such as analysis operators. In this embodiment, except in the exceptional case where the above predetermined person changes the setting of the heating gas supply mechanism operation setting unit 34, the setting of measurement conditions that stop the gas blowing operation from the heating gas supply mechanism 112 while a 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. Figure 2 is an enlarged view of the vicinity of the ionization chamber 11 of the mass spectrometer 1.

[0028] The ESI probe 111 is positioned such that its spray axis (the central axis of the direction of travel of charged droplets sprayed from the ESI probe 111) and the central axis of the desolvation tube 113 are perpendicular at the intersection point X. In this embodiment, the most preferred configuration is that the spray axis of the ESI probe 111 is vertical and the central axis of the desolvation tube 113 is horizontal. The heating gas supply probe 1123 is positioned such that the angle θ between the spraying direction of the heating gas supply probe 1123 (the central axis of the direction of travel of the heating gas) and the spray axis of the ESI probe 111 is between 60 and 80 degrees. The range of angle θ is based on the results of studies conducted by the applicant in a previous application (PCT / JP2021 / 030953). An angle θ of 60 degrees or more allows for easy positioning of the ESI probe 111 and the heating gas supply probe 1123 without physical interference between them. Furthermore, by keeping the angle θ at 80 degrees or less, the heating gas is blown onto the tip of the ESI probe 111, reducing the possibility of the liquid sample boiling inside the ESI probe 111. The desolvation tube 113, which is a capillary located in the partition wall between the ionization chamber 11 and the first intermediate vacuum chamber 12, is heated to a predetermined temperature by a heating block 1142 that forms part of the partition wall.

[0029] Furthermore, the heating gas supply probe 1123 and the heating block 1142 are positioned such 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 direction of gas blowing 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 droplet at a position between the tip of the ESI probe 111 and the intersection point X of the spray axis of the ESI probe 111 and the central axis of the desolvation tube 113 (at 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 distance L is also based on the results of studies 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 discharge occurring due to the tip of the ESI probe 111 and the tip of the heating gas supply probe 1123 being in close proximity can be reduced. Furthermore, by setting the distance L to 10 mm or less, in a typical ionization apparatus where the difference in height between the tip of the widely used 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 droplet at a position above the central axis of the desolvation tube 113 to promote desolvation and improve the sensitivity of ion measurement.

[0030] In this embodiment, a heating gas is blown onto the charged droplets sprayed from the tip of the ESI probe 111 before they reach the desolvation tube 113. This prevents the charged droplets from entering the analysis chamber 14 (first intermediate vacuum chamber 12, second intermediate vacuum chamber 13, and analysis chamber 14) from the desolvation tube 113 while still in droplet form. Furthermore, supplying heating gas to this location also prevents substances other than ions generated from the liquid sample (unwanted neutral molecules and ions present in the ionization chamber 11) from entering the analysis chamber 14 through the desolvation tube 113. This suppresses contamination of each chamber on the analysis chamber side and improves the robustness of the mass spectrometer 1.

[0031] Next, with reference to the flowchart in Figure 4, an example of measuring a liquid sample using the liquid chromatograph-mass spectrometer 100 of this embodiment will be explained.

[0032] When the user instructs the measurement of a liquid sample, the measurement condition setting unit 32 displays a list of compounds included 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 the measurement conditions and analysis parameters for that compound, as well as the operating parameters of the heating gas supply mechanism 112, from the compound database 311 and displays them on the screen of the display unit 5. The user makes any necessary changes to the measurement conditions, etc., and then finalizes the measurement conditions, etc. (Step 1). Once the user has finalized the measurement conditions, etc., the measurement condition setting unit 32 creates a batch file for performing the measurement and analysis of the sample and saves it in the storage unit 31.

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

[0034] After a batch file is created, when the user instructs the start of 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 measurement, the first intermediate vacuum chamber 12, the second intermediate vacuum chamber 13, and the analysis chamber 14 within the vacuum chamber are first evacuated to a predetermined vacuum level. At the same time, power is supplied to the heater 1122 of the heating gas supply mechanism 112, and gas is supplied from the gas supply source 1121 at a predetermined flow rate (e.g., 5 L / min) (Step 2). After power is supplied to the heater 1122, the temperature of the gas that has passed through the heater 1122 is measured by the temperature measuring unit 1124, and the amount of power supplied to the heater 1122 is adjusted so that the temperature stabilizes at a predetermined temperature (e.g., 400°C). The gas heated by the heater 1122 is blown into the ionization chamber 11. Furthermore, the drying gas supply mechanism 114 also supplies gas (dry gas) from the gas supply source 1141 and blows it into the ionization chamber 11 from the drying gas supply pipe 1143 (Step 3). By starting the blowing of the heating gas at the same time as or before the blowing of the drying gas, the airflow generated by the blowing of the drying gas prevents unwanted substances present in the ionization chamber 11 from entering the heating gas supply mechanism 112.

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

[0037] The various components in the liquid sample separated by the column of the liquid chromatograph 2 are sequentially introduced into the ESI probe 111 along with the mobile phase (step 4) and sprayed into the ionization chamber 11 as charged droplets (step 5). A heating gas is blown onto these charged droplets from the heating gas supply probe 1123 (step 6), thereby promoting desolvation. The ion stream 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 drying gas stream is blown from the drying gas supply tube 1143 to counteract the ion stream (step 7), and desolvation is further promoted as the ion stream passes through the heated desolvation tube 113.

[0038] When the measurement of the liquid sample is completed (step 8), the measurement control unit 33 stops the supply of the mobile phase to the liquid chromatograph 2. Subsequently, it stops the supply of gas from the gas supply source 1141 of the drying gas supply mechanism 114 (step 9). Simultaneously with this (or after the gas supply from gas supply source 1141 is stopped), it stops the supply of gas from the gas supply source 1121 of the heating gas supply mechanism 112 (step 10). By stopping the blowing of the heating gas at the same time as or after the blowing of the drying gas, it is prevented that unwanted substances present in the ionization chamber 11 will enter the heating gas supply mechanism 112 due to the airflow generated by the blowing of the drying gas.

[0039] Thus, in the liquid chromatograph mass spectrometer 100 of this embodiment, the supply of heating gas from the heating gas supply probe 1123 is started before the mobile phase or liquid sample is introduced from the liquid chromatograph 2 to the ESI probe 111, and the heating gas is continuously supplied while the mobile phase or liquid sample is being introduced to the ESI probe 111.

[0040] When various components in a 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 drying gas is blown from the drying gas supply mechanism 114 in a direction opposite to the ion flow. In an ionization apparatus configured as in this embodiment, where a heating gas supply mechanism 112, which is provided separately from the ESI probe 111, blows gas onto the charged droplets sprayed from the ESI probe 111 in a direction intersecting the direction in which the charged droplets are sprayed (the central axis from which the charged droplets are sprayed from the ESI probe 111 and the central axis from which the gas is blown from the heating gas supply mechanism 112 are on different axes), if gas is not blown from the heating gas supply probe 1123, some of the components in the liquid sample and the charged droplets of the mobile phase may enter the heating gas supply mechanism 112 due to the airflow generated in the ionization chamber 11, potentially contaminating the inside of the heating gas supply mechanism 112. If components from the liquid sample that entered the heating gas supply mechanism 112 during the previous measurement are blown onto the liquid sample for the next measurement along with the heating gas, contamination will occur. Furthermore, 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 continuously blows heating gas from the heating gas supply probe 1123 while the liquid sample is introduced into the ESI probe 111, so that components from the liquid sample and the mobile phase can be prevented from entering the heating gas supply mechanism 112 by this gas flow.

[0041] In the above measurement example, the measurement control unit 33 operates the heating gas supply mechanism 112 in synchronization with the start and end of the liquid sample measurement, blowing heating gas from the heating gas supply probe 1123 into the ionization chamber before the liquid sample and mobile phase are introduced into the ESI probe 111. However, other operating modes are also possible. For example, the supply of gas from the gas supply source 1121 of the heating gas supply mechanism 112 can be started and stopped simultaneously with the start and end of the supply of nebulizer gas by the nebulizer gas supply mechanism 1113 to the ESI probe 111. Since the nebulizer gas is used to spray the liquid sample and mobile phase introduced into the ESI probe 111 into the ionization chamber 11, blowing gas from the heating gas supply probe 1123 in synchronization with this can reliably prevent components of the liquid sample from entering the heating gas supply mechanism 112. In other words, any method can be adopted as long as the heating gas supply mechanism 112 can continue to blow gas while the liquid sample is being sprayed from the ESI probe 111.

[0042] In the measurement example above, only one liquid sample was measured, but in some cases, multiple liquid samples may be set in the autosampler and measured sequentially. In such measurements, a waiting period may be provided between measurements of liquid samples. For example, when performing gradient analysis with liquid chromatograph 2, after starting the measurement of one liquid sample, the mobile phase is equilibrated in liquid chromatograph 2. In such cases, if there is a period between measurements of liquid samples during which no liquid sample is introduced into the ESI probe 111 (waiting period), the blowing of heating gas from the heating gas supply probe 1123 to the ionization chamber 11 may be temporarily stopped, or the flow rate of the heating gas may be reduced from the measurement flow rate to the waiting flow rate (measurement flow rate > waiting flow rate). Of course, the same flow rate of gas may be blown from the heating gas supply probe 1123 to the ionization chamber 11 during both the measurement period and the waiting period.

[0043] Furthermore, in the above measurement example, in the heated gas supply mechanism 112, the gas supplied from the gas supply source 1121 was heated to a predetermined temperature by the heater 1122 and blown into the ionization chamber 11 from the heated gas supply probe 1123. However, the heater 1122 may be not energized, and the gas supplied from the gas supply source 1121 may be blown into the ionization chamber 11 without heating. For example, if the target component is easily decomposed or denatured by heat, it is preferable to blow an unheated gas. Also, when measuring such a target component, it is preferable not to energize the heating block 1142, to blow an unheated dry gas into the ion stream, and to introduce the ion stream into an unheated desolvation tube.

[0044] Furthermore, although the drying gas supply mechanism 114 was used in the above measurement example, it is not necessary to use the drying gas supply mechanism 114 (or the drying gas supply mechanism 114 may be provided but not operated during the measurement). In that case, it becomes less likely to generate an airflow that pushes the ion flow back into the ionization chamber 11 compared to when the drying gas is blown onto the ion flow. Therefore, when measuring without blowing the drying gas onto the ion flow, the flow rate of the gas blown from the heating gas supply probe 1123 into the ionization chamber 11 may be reduced compared to when the drying gas is blown onto the ion flow. For example, the measurement control unit 33 blows gas from the heating gas supply mechanism 112 at a predetermined first flow rate when gas is being blown from the drying gas supply mechanism 114, and the drying gas supply mechanism 114 and others If no gas is being supplied, the heating gas supply mechanism 112 should be configured to supply gas at a second flow rate lower than the first flow rate.

[0045] The above embodiments and measurement examples are all 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 operating parameters of the heating gas supply mechanism 112 (temperature, flow rate, etc. of the heating gas). However, the user may not be required to set the operating 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 measurement conditions such that the heating gas supply mechanism 112 operates with predetermined operating parameters, in accordance with 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. Furthermore, although the above embodiment includes a heating gas supply mechanism operation setting unit 34, this is also optional. The essential requirement in the above embodiment is that the heating gas supply mechanism 112 continues to blow gas (heated gas or unheated gas) while the liquid sample or mobile phase is sprayed from the ESI probe 111, regardless of whether or not the user is operating it. As long as this requirement is met, an appropriate configuration can be adopted.

[0047] Although this is described as a liquid chromatograph mass spectrometer 100, the same configuration can be adopted for a mass spectrometer that does not have a liquid chromatograph and directly introduces the liquid sample into the ESI probe. In that case, while the liquid sample is being sprayed from the ESI probe, the heating gas supply probe 1123 should be continuously blown into the ionization chamber.

[0048] In the above embodiment, an ionization apparatus (ESI source) having an ionization chamber 11 equipped with an ESI probe 111 was used. However, the same configuration can be adopted in an ionization apparatus (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 can be adopted in an ionization apparatus equipped with an ESI probe and a corona needle for APCI (a so-called dual ionization apparatus). Furthermore, in the above embodiment, the ESI probe 111 and the desolvation tube 113 were arranged so that the direction in which the liquid sample is sprayed from the ESI probe 111 and the central axis of the desolvation tube 113 are perpendicular (orthogonal arrangement). However, this is a preferred embodiment, and the present invention can be applied to other arrangements as well. Furthermore, the heating gas supply mechanism is provided separately from the ionization probe, and only needs to be configured to blow gas in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe (i.e., the central axis from which charged droplets are sprayed from the ionization probe and the central axis from which gas is blown from the heating gas supply mechanism are on different axes). In addition to the preferred configuration shown in the above embodiment, other appropriate configurations can be adopted.

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

[0050] [Aspect] It will be obvious to those skilled in the art that the exemplary embodiments described above are specific examples of the following embodiments.

[0051] (Section 1) One aspect of the present invention is an ionization apparatus arranged in an ionization chamber separated from an analysis chamber by a partition wall provided with an ion inlet, An ionization probe that sprays a liquid sample, A heating gas supply mechanism comprising a gas supply source and a heating unit for heating the gas supplied from the gas supply source, wherein the gas is blown in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe, A control unit controls the operation of the heating gas supply mechanism so that the heating gas supply mechanism continues to blow the gas from the heating gas supply mechanism regardless of whether or not the user is operating it, while the liquid sample is being sprayed from the ionization probe. It is 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 provided with an ion inlet, A step of introducing the liquid sample into the ionization probe and spraying it, The system includes a gas supply source and a heating unit for heating the gas supplied from the gas supply source, and a heating gas supply mechanism, provided separately from the ionization probe, continuously blows the gas in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe, regardless of whether or not the user is operating the system. Includes.

[0052] When a liquid sample is sprayed from an ionization probe inside the ionization chamber, an airflow is generated within the chamber. In conventional ionization devices, the timing of spraying the liquid sample from the ESI probe and the timing of blowing the heating gas from the heating gas supply mechanism can be set by the user as appropriate. However, in an ionization device where the heating gas supply mechanism, which is provided separately from the ESI probe, blows gas onto the charged droplets sprayed from the ESI probe in a direction intersecting the direction in which the charged droplets are sprayed (the central axis from which the charged droplets are sprayed from the ESI probe and the central axis from which the gas is blown from the heating gas supply mechanism are on different axes), if the heating gas supply mechanism does not blow gas while the liquid sample is being sprayed from the ionization probe, some of the charged droplets of the liquid sample will enter the heating gas supply mechanism due to the airflow generated inside the ionization chamber, thereby contaminating the inside of the heating gas supply mechanism. If the liquid sample that entered the inside of the heating gas supply mechanism during the previous measurement is sprayed onto the liquid sample for the next measurement along with the gas, contamination will occur. Furthermore, preventing such contamination requires cleaning the heating gas supply mechanism after each measurement, which is time-consuming and laborious.

[0053] In the ionization apparatus described in paragraph 1 and the ionization method described in paragraph 7, the operation of the ionization probe and the heating gas supply mechanism is controlled so that gas is continuously blown from the heating gas supply mechanism regardless of whether or not the user is operating it while the liquid sample is being sprayed from the ionization probe. In other words, the heating gas supply mechanism automatically starts blowing gas at the same time as or before the start of spraying the liquid sample, and continues blowing gas from the heating gas supply mechanism until the same time as or after the end of spraying the liquid sample. Therefore, the gas flow blown out from the heating gas supply mechanism prevents the liquid sample from entering the inside of the heating gas supply mechanism.

[0054] (Section 2) The ionizing apparatus referred to in paragraph 2 is the ionizing apparatus referred to in paragraph 1. The heating 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 blown out, and a non-heating operation in which the gas supplied from the gas supply source is blown out without being heated by the heating unit.

[0055] In the ionization apparatus described in paragraph 2, even when the target component to be measured is prone to decomposition or denaturation by heat, the heating gas supply mechanism can be operated without heating, thereby preventing the liquid sample from entering and contaminating the inside of the heating gas supply mechanism, and also promoting the desolvation of charged droplets.

[0056] (Section 3) The ionizing apparatus referred to in paragraph 3 is, in the ionizing apparatus referred to in paragraph 1 or 2, The ionization probe includes a nebulizer gas supply mechanism for supplying nebulizer gas for spraying 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 apparatus described in paragraph 3, the nebulizer gas supplied for spraying the liquid sample in the ESI probe is a nebulizer gas. supply By synchronizing the operation of the mechanism and operating the heating gas supply mechanism to continuously blow gas while the liquid sample is being sprayed by the nebulizer gas, it is possible to reliably prevent the sprayed liquid sample from entering the heating gas supply mechanism and contaminating it.

[0058] (Section 4) The ionizing apparatus referred to in paragraph 4 is an ionizing apparatus referred to in any of paragraphs 1 to 3, The control unit blows the gas from the heating gas supply mechanism at a predetermined measurement flow rate during the measurement period when the liquid sample is being measured, and blows the gas from the heating gas supply mechanism at a standby flow rate lower than the measurement flow rate during the standby period when the liquid sample is not being measured.

[0059] In the ionization apparatus described in paragraph 4, gas consumption can be reduced by decreasing the flow rate of gas blown from the heating gas supply mechanism during standby periods when liquid samples are not being measured. Furthermore, if nothing is sprayed from the ESI probe during standby periods when liquid samples are not being measured, or if the liquid sprayed from the ESI probe does not contaminate the heating gas supply mechanism, the standby flow rate may be set to zero (i.e., gas blowing may be stopped).

[0060] (Section 5) The ionizing apparatus relating to paragraph 5 is an ionizing apparatus relating to any of paragraphs 1 to 4, further comprising: A drying gas supply mechanism that blows gas in a direction opposite to the ion flow entering the ion inlet. It is equipped with.

[0061] In the ionization apparatus described in paragraph 5, the desolvation of the ion stream introduced into the ion inlet can be further accelerated by blowing a drying gas onto it.

[0062] (Section 6) The ionizing apparatus referred to in paragraph 6 is, in the ionizing apparatus referred to in paragraph 5, 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.

[0063] In the ionization apparatus described in paragraph 6, when gas is not being blown from the drying gas supply mechanism, charged droplets of the liquid sample are less likely to enter the heating gas supply mechanism compared to when gas is being blown. When gas is not being blown from the drying gas supply mechanism, the amount of gas used can be reduced by reducing the flow rate of gas blown from the heating gas supply mechanism. [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...Heating gas supply probe 1124...Temperature measurement section 113... Desolvent removal tube 114... Dry gas supply mechanism 1141... Gas supply source 1142...Heating block 1143... Drying gas supply pipe 12…First intermediate vacuum chamber 121... Aeon Guide 122... Skimmer 13…Second Intermediate Vacuum Chamber 131... Aeon Guide 14…Analysis room 141... Pre-stage quadrupole mass filter 142...Collision cell 143…Multipole rod electrode 144...Later stage quadrupole mass filter 145... Ion detector 2…Liquid Chromatography 3…Control and Processing Unit 31...Storage section 311... Compound Database 32...Measurement condition setting unit 33...Measurement Control Unit 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 formed by the spray axis of the ESI probe and the spray direction of the heating gas supply probe.

Claims

1. An ionization apparatus located in an ionization chamber separated from the analysis chamber by a partition wall equipped with an ion inlet, An ionization probe that sprays a liquid sample, A heating gas supply mechanism comprising a gas supply source and a heating unit for heating the gas supplied from the gas supply source, wherein the gas is blown in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe, A control unit controls the operation of the heating gas supply mechanism so that the operation of blowing the gas from the heating gas supply mechanism starts at the same time as or earlier than the start of spraying the liquid sample and continues until the same time as or later than the end of spraying the liquid sample. An ionization device equipped with the following features.

2. The ionization apparatus according to claim 1, wherein the heating 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 blown out, and a non-heating operation in which the gas supplied from the gas supply source is blown out without being heated by the heating unit.

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

4. The ionization apparatus according to claim 1, wherein the control unit blows the gas from the heating gas supply mechanism at a predetermined measurement flow rate during the measurement period in which the liquid sample is being measured, and blows the gas from the heating gas supply mechanism at a standby flow rate lower than the measurement flow rate during the standby period in which the liquid sample is not being measured.

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

6. The ionization apparatus according to 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 equipped with an ion inlet, A step of introducing the liquid sample into the ionization probe and spraying it, The heating gas supply mechanism has a gas supply source and a heating unit for heating the gas supplied from the gas supply source, and is provided separately from the ionization probe and blows the gas in a direction intersecting the direction in which the liquid sample is sprayed from the ionization probe. The heating gas supply mechanism starts blowing the gas at the same time as or earlier than when the spraying of the liquid sample begins, and continues blowing the gas until the same time as or later than when the spraying of the liquid sample ends. An ionization method that includes [a specific component].

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