JP2019212390A - Ion source and analysis device - Google Patents

Abstract

To provide an ion source capable of implementing a plurality of ionization schemes and also capable of obtaining high ionic strength.SOLUTION: An ion source according to the present invention has a first mode in which a sample solution and voltage are supplied to a first probe and a second mode in which a sample solution and voltage are supplied to a second probe. The flow rates of a sample solution and voltages supplied to the first probe and the second probe are different from each other between the first mode and the second mode.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an ion source and an analyzer using the same.

  Examples of ionization methods used for mass spectrometry include an electrospray method (hereinafter referred to as “ESI method”) and an atmospheric pressure chemical ionization method (hereinafter referred to as “APCI method”). In an atmospheric pressure ionization mass spectrometer, by using ESI, APCI, or the like, ions generated under atmospheric pressure are introduced into a vacuum system to analyze the mass of the ions.

  The ESI method generates a charged droplet by flowing a sample solution through a capillary to which a high voltage is applied and spraying the sample solution from the tip of the capillary, and generates ions by repeating evaporation and splitting of the charged droplet. It is. The ESI method is an ionization method that can be applied to a high molecular weight sample, a high polarity sample, and the like. In the ESI method, generally, a method of spraying a large amount of heated gas or the like to promote evaporation / vaporization of droplets is used in combination.

  The APCI method is a method in which a sample solution is heated and vaporized, and sample molecules are ionized by corona discharge. In the case of this system, charge transfer occurs between primary ions (ions different from sample molecules) generated by corona discharge and sample molecules, whereby the sample molecules are ionized. The APCI method can be applied to a low molecular weight sample having a small molecular weight or a low polarity sample having a small polarity compared to the ESI method.

  If ionization methods (for example, ESI method and APCI method) having different target samples and principles can be realized in one ion source, the range of substances to be measured and the application range of the ion source can be expanded. The following Patent Documents 1 and 2 describe techniques for realizing a plurality of ionization methods by one ion source as described above. In these documents, methods for executing ionization by the ESI method and ionization by the APCI method with one ion source are proposed.

Japanese Patent No. 4553011 US Pat. No. 7,488,953

  In Patent Document 1, an electrostatic spraying portion by ESI method and a needle electrode by APCI method are arranged in the same space, and ionization by ESI method and ionization by APCI method are executed simultaneously. In this document, a sample sprayed from an ESI probe is ionized by corona discharge of a needle electrode. The ESI probe has a structure in which the capillary is not heated so much because the sample may bump up if the capillary itself is heated too much. In contrast, APCI probes generally need to actively heat the capillary tip. Therefore, if the ESI probe is shared also in APCI ionization as in the same document, vaporization due to heating becomes insufficient in the APCI ionization step, and the sensitivity may be lowered.

  In Patent Document 2, as in Patent Document 1, the ESI probe is shared in APCI ionization. However, in this document, means for heating the spray region of the ESI probe is provided, thereby improving the APCI sensitivity. On the other hand, when the electric field interferes between the ESI probe and the APCI probe, the electric field at the time of ESI ionization may be disturbed, and the ESI sensitivity may decrease. A similar problem exists in Patent Document 1.

  Thus, although ion sources capable of performing both the ESI method and the APCI method have been proposed, there is a possibility that these conventional methods can obtain only a low ion intensity in each ionization method. . Therefore, conventionally, in analytical applications that require high sensitivity, it is common to use an ion source that uses a single ionization scheme.

  This invention is made | formed in view of the above subjects, and it aims at providing the ion source which can implement | achieve a several ionization system and can obtain high ionic strength.

  The ion source according to the present invention has a first mode for supplying the sample solution and voltage to the first probe, and a second mode for supplying the sample solution and voltage to the second probe. Between the first mode and the second mode, the flow rate and voltage of the sample solution supplied to the first probe and the second probe are different from each other.

  According to the ion source of the present invention, by switching the voltage supplied to each of the first probe and the second probe between the first mode and the second mode, the electric field interference at the probe tip is suppressed, High ionic strength can be obtained. Further, by switching the flow rate of the sample solution, it is possible to suppress problems such as clogging of the sample solution in the probe that is not being used while suppressing the consumption of the sample solution.

1 is a configuration diagram of a multi-ion source 1 according to Embodiment 1. FIG. In this example, the first ion source probe 3 or the second ion source probe 4 is configured as an ESI probe. In this example, the first ion source probe 3 or the second ion source probe 4 is configured as an APCI probe. 4 is a time chart for explaining the operation procedure of the multi-ion source 1. 6 is a configuration diagram of a multi-ion source 1 according to Embodiment 2. FIG. In this example, the first ion source probe 3 or the second ion source probe 4 is configured as an ESI probe. In this example, the first ion source probe 3 or the second ion source probe 4 is configured as an APCI probe. 4 is a time chart for explaining the operation procedure of the multi-ion source 1. 6 is a configuration diagram of a multi-ion source 1 according to Embodiment 3. FIG. In this example, the first ion source probe 3 or the second ion source probe 4 is configured as an ESI probe. In this example, the first ion source probe 3 or the second ion source probe 4 is configured as an APCI probe. 4 is a time chart for explaining the operation procedure of the multi-ion source 1. 4 is a graph showing the relationship between the flow rate of spray gas supplied to the first ion source probe 3 and the ion intensity by the second ion source probe 4. FIG. 10 is a diagram illustrating a configuration used in place of the first solution 5 and the first solution flow rate control unit 7 (or the second solution 6 and the second solution flow rate control unit 8) in the fourth embodiment. It is an operation | movement sequence of a liquid chromatography (LC). It is a figure explaining the relationship between the peak of the sample substance supplied with respect to an APCI probe, and the spray gas flow rate in an ESI probe. 10 is a time chart for explaining the operation of the multi-ion source 1 according to Embodiment 5. 1 is a schematic configuration diagram of an analyzer 100 that uses a multi-ion source 1. FIG. The analysis device 100 is a device that continuously analyzes a plurality of specimen samples 41. It is a flowchart explaining the procedure which determines the sample solution amount which the control part 10 supplies with respect to a probe. This is a configuration example when the second ion source probe 4 is an APCI ion source. It is XZ sectional drawing of FIG. It is a graph which illustrates the relationship between the ion intensity of an ESI mode, and the voltage of the needle electrode 21 in case the 1st ion source probe 3 is an ESI ion source. 10 is a configuration diagram of a multi-ion source 1 according to Embodiment 8. FIG. In the ESI probe of FIG. 10, it is a figure which shows the temperature change of the heat block 29 when gas supply is turned ON / OFF during implementing ESI ionization. It is a structural example of the heat block 29 with which the multi ion source 1 which concerns on Embodiment 9 is provided. It is a time chart explaining the operation | movement which the gas switching part 53 switches the flow path which supplies gas.

<Embodiment 1>
FIG. 1 is a configuration diagram of a multi-ion source 1 according to Embodiment 1 of the present invention. The multi ion source 1 includes an ion source chamber 2, a first ion source probe 3, and a second ion source probe 4. A first ion source probe 3 and a second ion source probe 4 are attached to the ion source chamber 2. As the first ion source probe 3 and the second ion source probe 4, various types of ionization probes such as an ESI method, an APCI method, an atmospheric pressure light method (APPI), and a sonic spray method (SSI) can be used.

  The multi ion source 1 further includes a first solution flow rate control unit 7 that controls the flow rate of the first solution 5, a second solution flow rate control unit 8 that controls the flow rate of the second solution 6, and a solution flow path switching unit 9. The solution flow path switching unit 9 switches the sample solution supplied to each probe. For example, when the first solution 5 flows through the first ion source probe 3, the second solution 6 flows through the second ion source probe 4, and when the second solution 6 flows through the first ion source probe 3, the second ion source. Solution supply can be controlled so that the first solution 5 flows through the probe 4. That is, it can be controlled so that one of the solutions always flows through either ion source probe. For example, a combination in which one of the first solution 5 and the second solution 6 is a sample solution containing an analysis target component and the other is a cleaning solution can be used.

  The control unit 10 controls the flow rate and switching timing of each solution by controlling each flow rate control unit and the solution flow path switching unit 9. The control unit 10 further includes power supplies 12 and 20 that apply a voltage to each probe.

  In FIG. 1, the XYZ axes are defined as shown for convenience of explanation. The longitudinal direction of the first ion source probe 3 was taken as the Z axis, the longitudinal direction of the second ion source probe 4 was taken as the Y axis, and the direction perpendicular to both the YZ axes was taken as the X axis. Ions ionized by the ion source probe travel in the extension direction of the X axis, and are detected / analyzed by a detector such as a mass spectrometer, for example.

  FIG. 2 is an example in which the first ion source probe 3 or the second ion source probe 4 is configured as an ESI probe. In the ESI ion source, a sample solution is introduced into the capillary 11, and ions are sprayed from the downstream end 13 of the capillary 11 while applying a high voltage from the power source 12 to the capillary 11. The value of the high voltage applied to the capillary 11 is generally about several kV (absolute value). When generating positive ions, a voltage of + several kV is applied to the capillary 11. When negative ions are generated, a voltage of −several kV is applied to the capillary 11. Generally, the inner diameter of the capillary 11 is set to 1 mm or less. Although depending on the inner diameter of the capillary 11, the flow rate of the sample solution is generally set in the range of nL / min order to about mL / min order. The sample solution introduced from the upstream of the pipe 14 in the direction of the arrow 15 is introduced into the capillary 11 via the connector 16.

  FIG. 3 shows an example in which the first ion source probe 3 or the second ion source probe 4 is configured as an APCI probe. The method of introducing the sample solution to the APCI ion source is the same as that of the ESI method, but a high voltage is not applied to the capillary 11. The sample solution exiting from the downstream end 13 of the capillary 11 is vaporized by the heating tube 17 and is atomized and sprayed from the downstream end 18 of the heating tube 17. The heating tube 17 has a heater 19 and can heat the sample solution to a high temperature of about 800 degrees at the maximum. Primary ions are generated by corona discharge generated by applying a high voltage from the power supply 20 to the needle electrode 21. Sample molecules are ionized by the transfer of charge between the primary ions and the sample molecules. The value of the high voltage applied to the needle electrode 21 is generally about several kV (absolute value). When generating positive ions, a voltage of + several kV is applied to the needle electrode 21. When generating negative ions, a voltage of −several kV is applied to the needle electrode 21.

  In such a multi-ion source having a plurality of probes, it is necessary to switch the probe for supplying the sample solution by switching the flow path of the sample solution in accordance with the timing of performing ionization in each ion source. Further, in order to suppress a decrease in sensitivity due to mutual interference between the electric fields in each ion source, it is considered necessary to switch the voltage supplied to each ion source as will be described later.

  FIG. 4 is a time chart for explaining the operation procedure of the multi-ion source 1. Here, it is assumed that the first ion source probe 3 is configured as an ESI ion source and the second ion source probe 4 is configured as an APCI ion source. The first solution flow rate control unit 7, the second solution flow rate control unit 8, and the control unit 10 operate while switching between mode 1 and mode 2 shown in FIG.

  In mode 1, the first ion source probe 3 ionizes the sample solution by the ESI method, and in mode 2, the second ion source probe 4 ionizes the sample solution by the APCI method. Since the mode side not in use does not generate ions, it is not necessary to flow the sample solution. However, if the solution does not flow through the capillary 11, the downstream end 13 is dried. In the case of a solution with a relatively small amount of contaminants such as a standard sample, the influence of drying is small, but in the case of a sample containing a large amount of contaminants such as salts and lipids such as a biological sample, impurities are precipitated by drying, The downstream end 13 may be clogged. In order to prevent this problem, it is necessary to flow a solution such as a cleaning solution to a mode-side probe that is not used. Therefore, in any mode, the sample solution is allowed to flow through the capillary 11.

  If the same amount of solution as in the ionization operation is allowed to flow even when ionization is not performed, there is a possibility that the side performing the ionization operation may be adversely affected. Therefore, the first solution flow rate control unit 7 and the second solution flow rate control unit 8 control the flow rate of the sample solution as follows: When in mode 1 (ESI ionization), the first ion source probe 3 has ESI ionization. An optimal flow rate A is supplied, and a flow rate D that has little influence on ESI ionization is supplied to the second ion source probe 4. In mode 2 (APCI ionization), a flow rate C that is optimal for APCI ionization is passed through the second ion source probe 4, and a flow rate B that is less affected by APCI ionization is passed through the first ion source probe 3.

  The voltage supplied by the power supplies 12 and 20 is similarly switched between modes. In mode 1, a voltage A optimum for ESI ionization is supplied to the capillary 11, and a voltage D having little influence on ESI ionization is supplied to the needle electrode 21. In mode 2, a voltage C optimum for APCI ionization is supplied to the needle electrode 21, and a voltage B having little influence on APCI ionization is supplied to the capillary 11.

<Embodiment 1: Summary>
In mode 1, the multi-ion source 1 according to Embodiment 1 provides a sample solution having a flow rate A and a voltage A to the first ion source probe 3 and a sample having a flow rate D to the second ion source probe 4. In the mode 2, the sample solution and the voltage B at the flow rate B are supplied to the first ion source probe 3 and the sample solution and the voltage C at the flow rate C to the second ion source probe 4 are provided. I will provide a. As a result, it is possible to prevent the ionization sensitivity of the probe on the side performing the ionization operation from being reduced due to electric field interference from the other side, and to prevent the capillary 11 from clogging in the probe on the side not performing the ionization operation. be able to. Therefore, a multi ion source capable of handling a wide range of samples can be realized with high sensitivity and high robustness.

  In the above description, an example in which the first ion source probe 3 is an ESI probe and the second ion source probe 4 is an APCI probe has been described. However, both probes are not limited to these types of ion sources. Both probes may be ion sources using the same method. In this case, high throughput can be achieved, such as performing ionization while cleaning one. Moreover, while both probes use the same system, the structure which differs in the flow conditions which implement ionization may be sufficient. Specifically, there are examples in which the inner diameters of the capillaries are different. Thereby, ionization from which flow conditions differ can be implemented with the same ion source. The same applies to the following embodiments.

  The flow rate and voltage shown in FIG. 4 may be set to different values between the same mode (ionization method). For example, when the target component is different between the first mode 1 and the second mode 1, the optimum conditions of the flow rate and voltage may be different from each other, so such a method is effective. The same applies to the following embodiments.

<Embodiment 2>
FIG. 5 is a configuration diagram of a multi-ion source 1 according to Embodiment 2 of the present invention. The multi ion source 1 according to the second embodiment supplies a spray gas to each ionization probe. The multi ion source 1 includes a gas source 22, a first gas flow rate control unit 23, and a second gas flow rate control unit 24. Since the other configuration is the same as that of the first embodiment, the difference will be mainly described below.

  The gas supplied from the gas source 22 is branched to the first gas flow rate control unit 23 and the second gas flow rate control unit 24. Each flow rate control unit controls the gas flow rate according to a procedure described later, and the gas having the controlled flow rate is introduced into the first ion source probe 3 and the second ion source probe 4. In general, an inert gas such as nitrogen or argon is used as the gas supplied from the gas source 22. FIG. 5 shows an example in which the same gas is supplied to both probes. However, when different gases are supplied to both probes, the gas flow path system and the solution flow path system (5 to 9) are also shown. A similar configuration may be used.

  FIG. 6 is an example in which the first ion source probe 3 or the second ion source probe 4 is configured as an ESI probe. In FIG. 6, a spray tube 25 is arranged concentrically with the capillary 11. Gas is introduced into the spray tube 25 through the port 26 as shown by an arrow 27. The introduced gas is sprayed from a gap between the outer diameter of the capillary 11 and the inner diameter of the downstream end 28 of the spray tube 25 (a spray gas). This gas promotes vaporization of the sample solution sprayed from the downstream end 13 of the capillary 11 and improves ionization efficiency. That is, the sensitivity is improved.

  FIG. 7 shows an example in which the first ion source probe 3 or the second ion source probe 4 is configured as an APCI probe. Also in FIG. 7, the spray tube 25 is arranged concentrically with the capillary 11, and the sample solution can be efficiently directed toward the needle electrode 21 by the flow of the spray gas. This promotes vaporization of the sample solution and improves sensitivity.

  FIG. 8 is a time chart for explaining the operation procedure of the multi-ion source 1. The solution flow rate control and voltage control are the same as in FIG. The first gas flow rate control unit 23 and the second gas flow rate control unit 24 control the flow rate of the spray gas as follows: When in mode 1, the first ion source probe 3 has a flow rate E optimum for ESI ionization. The second ion source probe 4 is supplied with a flow rate H that has little influence on ESI ionization. In mode 2, the second ion source probe 4 is supplied with a flow rate G optimum for APCI ionization, and the first ion source probe 3 is supplied with a flow rate F that has little influence on APCI ionization.

  As shown in FIG. 4, when the sample solution continues to flow through the probe on the side where the ionization operation is not performed, dripping or the like occurs depending on the flow rate. Therefore, as in the second embodiment, it is effective to vaporize the sample solution by flowing the spray gas to the probe on the side where the ionization operation is not performed.

<Embodiment 3>
FIG. 9 is a configuration diagram of the multi-ion source 1 according to Embodiment 3 of the present invention. The multi-ion source 1 according to the third embodiment supplies two systems of gas to the first ion source probe 3 and supplies two systems of gas to the second ion source probe 4. In the third embodiment, the gas supplied from the gas source 22 is branched into four branches. The first gas flow rate controller 23 is divided into two parts 23-a and 23-b, and the second gas flow rate controller 24 is divided into two parts 24-c and 24-d. Since other configurations are the same as those of the second embodiment, differences will be mainly described below.

  FIG. 10 is an example in which the first ion source probe 3 or the second ion source probe 4 is configured as an ESI probe. In FIG. 10, a heat block 29 is disposed outside the capillary 11. The heat block 29 has a heater 30 and can heat the heating gas flowing in the heat block 29 to a high temperature of about 800 degrees at the maximum. A heated gas is introduced into the heat block 29 through the port 31 as indicated by an arrow 32. The introduced heated gas is sprayed from the downstream end 33 of the heat block 29. This heated gas further promotes vaporization of the sample solution sprayed from the downstream end 13 of the capillary 11 and further improves the ionization efficiency. That is, the sensitivity is further improved.

  FIG. 11 shows an example in which the first ion source probe 3 or the second ion source probe 4 is configured as an APCI probe. In FIG. 11, auxiliary gas is introduced from a port 31 as indicated by an arrow 32. By flowing the auxiliary gas inside the heating tube 17, the gas flow inside the heating tube 17 is stabilized, thereby improving the sensitivity.

  FIG. 12 is a time chart for explaining the operation procedure of the multi-ion source 1. The solution flow rate control and voltage control are the same as in FIG. The first gas flow rate control unit 23-a and the second gas flow rate control unit 24-c respectively control the flow rates a and c of the spray gas as described with reference to FIG. The first gas flow rate controller 23-b controls the heating gas flow rate b supplied to the first ion source probe 3, and the second gas flow rate controller 24-d supplies the second ion source probe 4. The auxiliary gas flow rate d is controlled. In mode 1, the first ion source probe 3 is supplied with a heating gas having a flow rate I optimum for ESI ionization, and the second ion source probe 4 is supplied with an auxiliary gas having a flow rate L that has little influence on ESI ionization. . In mode 2, the second ion source probe 4 is supplied with an auxiliary gas at a flow rate K optimum for APCI ionization, and the first ion source probe 3 is supplied with a heating gas at a flow rate J that has little influence on APCI ionization. .

  FIG. 13 is a graph showing the relationship between the flow rate of the spray gas supplied to the first ion source probe 3 and the ion intensity by the second ion source probe 4. Here, the ESI ion source using the spray gas shown in FIG. 6 or the like is used as the first ion source probe 3, and the APCI ion source shown in FIG. 3 or the like is used as the second ion source probe 4.

  It can be seen from FIG. 13 that the sensitivity is maximum when the spray gas flow rate is 0, and the sensitivity decreases as the spray gas flow rate increases. The cause of the decrease in APCI sensitivity is considered to be that the sample molecules present in the area where APCI ions are generated are diluted with the spray gas of the first ion source probe 3. Normally, ESI spray gas is generally flowed at about 0.5 to 10 L / min. Therefore, when an optimal spray gas flow rate for the ESI method is applied to the ESI ion source in the APCI mode, APCI ions are flowed. Sensitivity is greatly reduced. Therefore, it is essential to switch the flow rate between modes as shown in FIG. When the result of FIG. 13 is taken as an example, for example, in order to obtain a sensitivity of about 80% of the maximum sensitivity in the APCI mode, it is necessary to suppress the spray gas of the first ion source probe 3 to about 0.3 L / min. I can say that.

<Embodiment 4>
According to the result shown in FIG. 13, when the sensitivity in the APCI mode (mode 2) is to be maintained to the maximum, the spray gas flow rate in the ESI probe needs to be zero. On the other hand, if the spray gas flow rate in the ESI probe is set to 0 during the entire period in which mode 2 is being performed, liquid dripping or the like may occur as described in the second embodiment. Therefore, in Embodiment 4 of the present invention, a configuration example will be described in which the sample solution is supplied in a pulse form to the APCI probe in the APCI mode, and the spray gas flow rate in the ESI probe is set to 0 only in the vicinity of the pulse peak. Since other configurations of the multi-ion source 1 are the same as those in the second to third embodiments, differences will be mainly described below.

  FIG. 14 is a diagram illustrating a configuration used in place of the first solution 5 and the first solution flow rate control unit 7 (or the second solution 6 and the second solution flow rate control unit 8) in the fourth embodiment. A sample is injected into the sample injection unit 39. The mobile phases 34 and 35 are fed by pumps 36 and 37 and mixed by a mixer 38. The sample is sent to the separation column 40 by the flow of the mobile phases 34 and 35. The mixing ratio in the mixer 38 is adjusted by the flow rate ratio of the pumps 36 and 37. As the mobile phases 34 and 35, for example, one is often water and the other is an organic solvent such as methanol or acetonitrile.

  FIG. 15 is an operation sequence of liquid chromatography (LC). With the configuration shown in FIG. 14, liquid chromatography can be performed. After the separation column 40 is washed and equilibrated with water or an organic solvent used as the mobile phases 34 and 35, a sample is injected into the separation column 40. The sample components are eluted from the separation column 40 with a solution in which the mobile phases 34 and 35 or both are mixed. When elution is performed, the peak of the sample substance to be eluted can be obtained at different times as shown in FIG. 15 by changing the mixing ratio of the mobile phases 34 and 35 with time (LC separation). By disposing the multi-ion source 1 as shown in FIG. 1 downstream of the configuration of FIG. 14, the sample material can be supplied in pulses to the APCI probe in mode 2.

  FIG. 16 is a diagram illustrating the relationship between the peak of the sample material supplied to the APCI probe and the spray gas flow rate in the ESI probe. From the type of the separation column 40, the mixing ratio of the mobile phases 34 and 35, the length of the piping, etc., the LC peak timing (retention time) corresponding to the sample component can be uniquely defined. That is, the ionization timing can be specified for each analysis target component. Accordingly, in mode 2, the spray gas flow rate in the ESI probe is set to 0 near the peak of the sample material supplied to the APCI probe, and the spray gas is continuously supplied to the ESI probe in other periods in mode 2.

  Taking the result of FIG. 13 as an example, the atomizing gas in the first ion source probe 3 (ESI) is switched to 0 (or low flow rate) in accordance with the APCI ion generation (LC peak) in the second ion source probe 4. Thereby, the sensitivity fall of APCI ion can be prevented. At the same time, the flow rate of the sample solution on the side where the ionization operation is not performed may be switched. The same control may be performed with respect to the gas flow rate other than the spray gas.

  The first solution 5 and the first solution flow rate control unit 7 may be replaced with the configuration of FIG. 14, and the second solution 6 and the second solution flow rate control unit 8 may be replaced with the configuration of FIG. When both are replaced, the separation column 40 may be installed downstream of the solution flow path switching unit 9. By replacing both of these, it is possible to prevent a decrease in ion sensitivity in any mode.

  In the fourth embodiment, it has been described that the sample solution is supplied in a pulse form to the probe by the configuration of the liquid chromatography. Other configurations may be used as long as the same operation can be realized. For example, the sample solution may be supplied in a pulse form to the probe by supplying the sample solution using an injection mechanism. That is, it is only necessary to adjust the timing for supplying the sample solution to the probe.

<Embodiment 5>
FIG. 17 is a time chart for explaining the operation of the multi-ion source 1 according to Embodiment 5 of the present invention. In the fifth embodiment, after cleaning by supplying a sample solution to the ionization probe on the side not performing the ionization operation, the solution flow rate is switched to 0 (or low flow rate). The configuration of the multi-ion source 1 is the same as in the first to fourth embodiments.

  In the fifth embodiment, the sample solution on the side not performing the ionization operation is flowed at a flow rate that does not affect the side performing the ionization operation, and then switched to 0 (or low flow rate). That is, the flow rate of the sample solution is gradually changed toward zero. As described in the first embodiment, in order to suppress clogging due to contaminants, it is desirable to perform cleaning by supplying the sample solution to the unused probe for a certain period of time. On the other hand, it is considered that there is no problem even if the flow rate of the sample solution is switched to 0 (or low flow rate) after the cleaning is sufficiently completed. Therefore, in FIG. 17, the sample solution on the side where the ionization operation is not performed is not changed to 0 immediately, but gradually changed toward 0. Since the same effect can be exhibited if it is gradually changed, it is not always necessary to switch the flow rate stepwise. Similar switching may be performed for various gases.

  In FIG. 17, the flow rate is returned to the use state at the timing of shifting from the non-use side to the use side (where the first ion source probe 3 is changed from the OFF state to the flow rate A or the second ion source probe). 4), the flow rate may be restored by shifting the timing. For example, the sample solution of the first ion source probe 3 may be returned slightly earlier than the mode 2 is shifted to the mode 1.

  According to the fifth embodiment, the probe on the side not performing the ionization operation is washed to suppress clogging of the sample solution and the sample solution or gas is applied to the probe on the side not performing the ionization operation. Extra consumption due to continuing to flow can be suppressed.

<Embodiment 6>
An analyzer using the multi-ion source 1 may inspect a plurality of specimens continuously. Depending on the analysis procedure at this time, the same ionization probe may be used continuously. For example, a pattern in which nine specimens that ionize a sample using an ESI probe are inspected in succession, and then one specimen that ionizes the sample is examined using an APCI probe is conceivable. In this analysis procedure, as described in the first to fifth embodiments, if the APCI probe is continuously washed while using the ESI probe, the sample solution is excessively consumed. Therefore, in the sixth embodiment of the present invention, a procedure for suppressing the amount of the sample solution used for cleaning the probe on the side not performing the ionization operation will be described. The configuration of the multi-ion source 1 is the same as in the first to fifth embodiments.

  FIG. 18 is a schematic configuration diagram of an analyzer 100 that uses the multi-ion source 1. The analysis device 100 is a device that continuously analyzes a plurality of specimen samples 41. A barcode label 42 is attached to the container of the specimen sample 41. The recognition means 43 (for example, a barcode reader) can read information (specimen type, measurement condition, etc.) described by the barcode label 42. The control unit 10 selects an ionization probe to be used according to the data read by the recognition means 43, and sets the flow rate, voltage, etc. of the sample solution / gas. The dispensing device 44 aspirates the specimen sample 41, moves it as indicated by an arrow 45, and discharges it to the sample injection unit 39.

  By arranging a plurality of recognition means 43 or moving the specimen sample 41 or the recognition means 43 as indicated by an arrow 46, the barcode labels 42 of the plurality of specimen samples 41 before analysis can be read. Thereby, the control part 10 can grasp | ascertain beforehand the analysis procedure implemented from now on. That is, the control part 10 can grasp | ascertain beforehand the frequency | count of using the same probe continuously. The control unit 10 saves the sample solution used for cleaning the probe on the side where the ionization operation is not performed according to the procedure described below.

  FIG. 19 is a flowchart illustrating a procedure for determining the amount of the sample solution supplied from the control unit 10 to the probe. It is assumed that the first ion source probe 3 is an ESI probe and the second ion source probe 4 is an APCI probe. Hereinafter, each step of FIG. 19 will be described.

(FIG. 19: Step S1901)
The control unit 10 acquires the number of times that the ESI probe is continuously used according to the description of the barcode label 42. If the number of times the ESI probe is continuously used is n times or more, the process proceeds to step S1904, and if it is less than n times, the process proceeds to step S1902. The numerical value of n is appropriately determined according to the degree of saving the sample solution.

(FIG. 19: Steps S1902 to S1903)
The control unit 10 performs ESI analysis using the first ion source probe 3 and cleans the sample solution by flowing it through the second ion source probe 4 (S1902). If the ESI analysis has been completed for all the specimen samples 41 to be subjected to ESI analysis, the process proceeds to step S1909, and if not completed, step S1902 is repeated (S1903).

(FIG. 19: Steps S1904 to S1905)
The control unit 10 stops the sample solution supplied to the second ion source probe 4 (S1904). You may stop after washing | cleaning. The control unit 10 performs ESI analysis using the first ion source probe 3 (S1905).

(FIG. 19: Steps S1906 to S1907)
The control unit 10 determines whether or not the ESI analysis currently being performed is the (n-1) th time (S1906). In the case of the (n-1) th time, the control unit 10 cleans the second ion source probe 4 before starting the APCI analysis by flowing the sample solution to the second ion source probe 4 (S1907).

(FIG. 19: Steps S1906 to S1907: Supplement)
When it is necessary to wash the second ion source probe 4 a plurality of times, for example, the determination criterion in step S1906 may be changed to n-2 times. That is, the APCI probe may be washed in a part while the ESI analysis is performed, and the washing may be stopped in the remaining part.

(FIG. 19: Steps S1908 to S1909)
The control unit 10 determines whether or not the ESI analysis currently being performed is the nth time (S1908). In the case of the nth time, the control unit 10 cleans the first ion source probe 3 by flowing the sample solution to finish the ESI analysis, and performs the APCI analysis using the second ion source probe 4.

  According to the procedure described above, when the ESI analysis is continuously performed, the amount of the sample solution used for cleaning the APCI probe can be saved. Here, the procedure for adjusting the number of times of APCI cleaning according to whether or not the ESI probe is continuously used for a predetermined number of times or more has been described. However, when the APCI probe is continuously used, the same procedure can be used by replacing the probe. it can. The same applies when other probes are used. Further, the same procedure can be performed for the gas flow rate.

<Embodiment 7>
As described in the first embodiment, the APCI probe includes the needle electrode 21 that discharges the sample solution sprayed from the tip of the capillary 11. An electric field is generated between the ESI probe and the needle electrode 21 (or between an entrance electrode 47 and a needle electrode 21 described later) by the voltage applied when the ESI analysis is performed, and the electric field adversely affects the ESI analysis. May give. In Embodiment 7 of the present invention, a procedure for suppressing such adverse effects will be described.

  FIG. 20 is a configuration example when the second ion source probe 4 is an APCI ion source. Although the configuration shown in FIG. 20 is the same as that described in the first embodiment, the arrangement of the needle electrodes 21 is schematically shown for convenience of description.

  21 is a cross-sectional view taken along XZ in FIG. In FIG. 21, the first ion source probe 3 extends in the Z direction, the second ion source probe 4 extends in the Y direction, and a detector such as a mass spectrometer is disposed at the tip in the X direction. When the detector is a mass spectrometer, the generated ions are generally introduced into a vacuum. For example, ions are introduced from the hole 48 of the entrance electrode 47. In order to maintain the vacuum, the hole 48 of the inlet electrode 47 is generally set to have an inner diameter of about 1 mm or less. Since the sample solution is sprayed inside the ion source chamber 2, it is often covered with a cover 49 or the like as shown in FIG. By configuring the cover 49 with a transparent material such as heat resistant glass, the inside of the ion source chamber 2 can be observed.

  FIG. 22 is a graph illustrating the relationship between the ion intensity in the ESI mode and the voltage of the needle electrode 21 when the first ion source probe 3 is an ESI ion source. As shown in FIG. 22, if a voltage of 0.1 kV or more is not applied to the needle electrode 21, a significant decrease in sensitivity occurs. The cause is considered as follows.

  ESI ionization is caused by the electric field between the capillary 11 and the inlet electrode 47. The voltage applied to the entrance electrode 47 is about several tens to several hundreds volts. At this time, if the needle electrode 21 is 0 V, the electric field between the capillary 11 and the needle electrode 21 becomes relatively strong due to the potential difference, the tip shape, and the like, and the influence of the electric field moves toward the entrance electrode 47. It is considered that the amount of ions sprayed is extremely reduced. This causes a decrease in sensitivity. Therefore, by applying a voltage having the same polarity as that of the capillary 11 to the needle electrode 21 during the ESI analysis, an electric field repelling between the needle electrode 21 and the capillary 11 is generated, and thereby the ion flow. Can be prevented from going to the needle electrode 21. Therefore, it is desirable to set the voltage B shown in FIG. 4 to at least about 0.1 kV, not at least 0, for example.

<Eighth embodiment>
FIG. 23 is a configuration diagram of the multi-ion source 1 according to Embodiment 8 of the present invention. The multi ion source 1 according to the eighth embodiment includes a third ion source probe 50 in addition to the configurations described in the first to seventh embodiments. Depending on the type of ion source, the cleaning efficiency may differ depending on the cleaning solution. In that case, the third solution 51 and the third solution flow rate control unit 52 are further provided, and different cleaning liquids are supplied to the third ion source probe 50. May be flushed. Alternatively, by switching between the first solution 5 and the second solution 6, the same cleaning solution may be supplied to two probes that are not performing the ionization operation. A power source 58 that applies a voltage to the third ion source probe 50 may be provided. When the gas supply as shown in FIGS. 5 and 9 is also necessary, the gas may be supplied to the third ion source probe 50.

  The number of ion source probes is arbitrary, and four or more ion source probes may be provided. The control procedure for each ion source probe is the same as in the first to seventh embodiments. A plurality of ionization probes can simultaneously perform ionization.

<Embodiment 9>
FIG. 24 is a diagram showing a temperature change of the heat block 29 when the gas supply is turned ON / OFF during ESI ionization in the ESI probe of FIG. The temperature of the heat block 29 that has been balanced by flowing the gas into the heat block 29 heated by the heater 30 increases instantaneously when the gas is turned off, and returns to the original temperature for about 3 minutes. I need it. On the other hand, when the gas is turned on again, the temperature drops instantaneously, and again it takes about 3 minutes to return to the temperature.

  When the control as shown in FIG. 12 is performed under the above premise, a time during which the temperature is unstable at the time of switching between modes occurs for about several minutes. The unstable state becomes more prominent as the flow rate difference at the time of switching increases. Since temperature variation leads to sensitivity variation, it is desirable to suppress as much as possible. By shifting the flow rate switching timing and mode switching (analysis start) timing of various fluids (for example, the analysis starts after the temperature is stabilized), the influence of sensitivity variations can be suppressed to some extent, but on the other hand, there is a concern that throughput may decrease due to waiting time. The Therefore, in the ninth embodiment of the present invention, a configuration example for stabilizing the temperature of the heat block 29 will be described.

  FIG. 25 is a configuration example of the heat block 29 provided in the multi-ion source 1 according to the ninth embodiment. In the ninth embodiment, the heat block 29 has two gas flow paths inside. In order to simplify the drawing, heaters are not shown. The gas switching unit 53 switches which channel the gas is supplied to.

  FIG. 26 is a time chart for explaining the operation in which the gas switching unit 53 switches the flow path for supplying the gas. When the ESI probe is used, gas is supplied to the flow path 54 and ionization is promoted by the heated gas indicated by the arrow 56. When the ESI probe is not used, the gas is supplied to the flow path 55 without changing the gas flow rate, and the gas is sprayed in the direction of the arrow 57 (the direction where there is no ion source probe on the use side). As a result, the ion source probe in use can be prevented from being affected by dilution or the like. Since only the flow path is switched without changing the gas flow rate, the temperature change of the heat block 29 can be suppressed. Accordingly, temperature instability as described with reference to FIG. 24 can be suppressed, and throughput can be ensured. Such channel switching is also effective for other gases and solutions.

<Modification of the present invention>
The present invention is not limited to the embodiments described above, and includes various modifications. For example, the above-described embodiment has been described in detail for easy understanding of the present invention, and is not necessarily limited to one having all the configurations described. Further, a part of the configuration of an embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of an embodiment. In addition, it is possible to add, delete, and replace other configurations for a part of the configuration of each embodiment.

  In the above embodiment, the example in which the first ion source probe 3 extends in the Z direction and the second ion source probe 4 extends in the Y direction has been described. However, this arrangement is not essential, for example, the first ion source. The probe 3 and the second ion source probe 4 may be reversed. Furthermore, it is not limited to an arrangement relationship in which both are orthogonal to each other, but may be an arrangement relationship of other angles.

  In the sixth embodiment, the example in which the barcode label 42 describes the analysis procedure has been described. However, other data recording means may be used. For example, it is conceivable to use an RFID tag or the like instead of the barcode.

  The control unit 10 may be realized by hardware, for example, by designing a part or all of it with an integrated circuit. Or you may implement | achieve by a software, when a processor interprets and executes the program which implement | achieves each function. Information such as programs, tables, and files for realizing each function can be stored in a memory, a hard disk, a recording device such as an SSD (Solid State Drive), or a recording medium such as an IC card or an SD card.

DESCRIPTION OF SYMBOLS 1 ... Multi ion source 2 ... Ion source chamber 3 ... 1st ion source probe 4 ... 2nd ion source probe 5 ... 1st solution 6 ... 2nd solution 7 ... 1st solution flow rate control part 8 ... 2nd solution flow rate control part DESCRIPTION OF SYMBOLS 9 ... Solution flow path switching part 10 ... Control part 11 ... Capillary 12 ... Power supply 13 ... Downstream end 14 ... Pipe 16 ... Connector 17 ... Heating pipe 18 ... Downstream end 19 ... Heater 20 ... Power supply 21 ... Needle electrode 22 ... Gas source 23 ... 1st gas flow control part 24 ... 2nd gas flow control part 25 ... Spray pipe 26 ... Port 28 ... Downstream end 29 ... Heat block 30 ... Heater 31 ... Port 33 ... Downstream end 34 ... Mobile phase 35 ... Mobile phase 36 ... Pump 37 ... Pump 38 ... Mixer 39 ... Sample injection part 40 ... Separation column 41 ... Sample sample 42 ... Bar code label 43 ... Recognition means 44 ... Dispensing device 47 ... Inlet electrode 48 ... Hole 49 ... Cover 50 ... Third ion Probe 51 ... third solution 52 ... third solution flow rate controller 53 ... gas switching section 54 ... flow path 55 ... flow path 58 ... Power

Claims (10)

First and second probes through which the sample solution passes,
A flow rate controller for controlling the flow rate of the sample solution passing through the first and second probes;
A power supply for supplying a voltage to the first and second probes;
With
The flow rate controller includes a first mode in which a first flow rate sample solution is allowed to flow through the first probe and a second flow rate sample solution is allowed to flow through the second probe, and a third flow rate sample solution is allowed to flow into the first probe. And is configured to be able to switch between a second mode in which a fourth flow rate of the sample solution is allowed to flow through the second probe,
The power supply supplies a first voltage to the first probe and a second voltage to the second probe when the flow rate controller performs the first mode,
The power supply supplies a third voltage to the first probe and a fourth voltage to the second probe when the flow rate controller executes the second mode. Ion source. The ion source further includes a gas supply unit that supplies gas to the vicinity of the downstream ends of the first and second probes,
The gas supply unit supplies the gas at the first gas flow rate to the vicinity of the downstream end of the first probe and the second probe when the flow rate control unit performs the first mode. Supplying the gas at the second gas flow rate to the vicinity of the downstream end;
The gas supply unit supplies the gas at a third gas flow rate to the vicinity of the downstream end of the first probe when the flow rate control unit performs the second mode, and The ion source according to claim 1, wherein the gas having a fourth gas flow rate is supplied to the vicinity of the downstream end. The gas supply unit supplies the first type of gas to the vicinity of the downstream end of the first probe, and differs from the first type to the vicinity of the downstream end of the second probe. The ion source according to claim 2, wherein the type of gas is supplied. The flow rate control unit includes a control mechanism for controlling timing of supplying the sample solution to the second probe,
The control mechanism intermittently supplies the sample solution of the fourth flow rate to the second probe when the flow rate control unit is performing the second mode,
The gas supply unit is configured such that when the flow rate control unit performs the second mode and the control mechanism supplies the sample solution with the fourth flow rate to the second probe, Supplying the gas at the third gas flow rate to the vicinity of the downstream end;
When the control mechanism is not supplying the sample solution with the fourth flow rate to the second probe, the gas supply unit has the first gas flow rate with respect to the vicinity of the downstream end of the first probe. Supplying the gas,
The ion source according to claim 2, wherein the third gas flow rate is smaller than the first gas flow rate. The flow rate control unit gradually changes the flow rate of the sample solution flowing through the first probe from the first flow rate to the third flow rate when switching from the first mode to the second mode,
The flow rate control unit gradually changes the flow rate of the sample solution passed through the second probe from the fourth flow rate to the second flow rate when the second mode is switched to the first mode. The ion source according to 1. The second probe includes an electrode disposed in the vicinity of the downstream end of the first probe,
The said power supply applies the voltage which is the same polarity as the said 1st voltage, and is not zero with respect to the said electrode, when the said flow control part implements the said 1st mode. The described ion source. The ion source further comprises a heating block for heating the sample solution passing through the first probe,
The heating block includes first and second flow paths through which heated gas passes,
The first flow path is arranged to pass the heated gas toward the downstream end of the first probe,
The second flow path is arranged to pass the heated gas away from the downstream end of the first probe and away from the downstream end of the second probe,
The heating block further includes a gas switching unit that switches between flowing the heated gas into the first flow path and the second flow path,
The gas switching unit causes the heating gas to flow through the first flow path when the flow rate control unit implements the first mode, and the second flow rate when the flow rate control unit implements the second mode. The ion source according to claim 1, wherein the heated gas is caused to flow through a path. The first probe is configured to ionize the sample solution using a first ionization method,
The ion source according to claim 1, wherein the second probe is configured to ionize the sample solution using a second ionization method different from the first ionization method. The ion source according to claim 1,
A dispensing mechanism for taking out the sample solution from a container containing the sample solution and delivering it to the first and second probes;
A condition acquisition unit for acquiring a condition for designating which of the first mode and the second mode should be performed by the flow rate control unit when the dispensing mechanism takes out the sample solution from the container;
With
The flow rate control unit implements the first mode and the second mode according to the condition acquired by the condition acquisition unit. When the condition specifies that the first mode is continuously performed a plurality of times, the flow rate control unit may include the second probe on the second probe in a part of the times when the first mode is performed. 10. The analyzer according to claim 9, wherein a sample solution having a second flow rate is allowed to flow, and a sample solution less than the second flow rate is allowed to flow or not to flow at all in the remaining portion of the first mode. .