Ion source, mass spectrometer, and ion source control method

Abstract

The object of the present invention is to provide an ion source and a control method thereof that can accurately and efficiently determine whether the front end position of the downstream side of a capillary is appropriate. The ion source of the present invention measures the current generated by the voltage applied by a power supply to the capillary when a sample is not introduced into the capillary, and outputs exposure amount information indicating that the exposure amount of the capillary is appropriate when the current is within the allowable range, and outputs the protrusion amount information indicating that the protrusion amount is inappropriate when the current is not within the allowable range (refer to FIG. 1 ).

Description

Technical Field

[0001] The present invention relates to an ion source for ionizing a sample. Background Art

[0002] The electrospray method (hereinafter referred to as "ESI method"), which is a general ionization method used in mass analysis, is a method in which a sample solution is introduced from the upstream end of a capillary and ions or droplets are sprayed from the downstream end by an electric field, etc. In order to improve the ionization efficiency, a gas spray tube is sometimes arranged outside the capillary to spray gas, or a heated gas is sprayed on the ions or droplets sprayed from the capillary.

[0003] Since the inner diameter of the capillary is very small, the possibility of clogging is high, and the capillary needs to be replaced frequently according to the type of sample solution, usage conditions, etc. However, the capillary replacement operation of the existing ESI ion source is complicated, and the reproducibility of the position of the downstream end of the capillary after replacement will affect the reproducibility of the detection sensitivity. This is because the position of the downstream end of the capillary of the mass spectrometer relative to the ion introduction port has a great influence on the detection sensitivity.

[0004] The following patent document 1 describes a technique for adjusting the position of the downstream end of a capillary. In this document, the capillary and the joint are fastened and integrated in advance, and the joint can be moved in the front-rear direction by rotating and screwing it relative to the manifold (the position of the downstream end of the capillary can be adjusted in a state where the capillary is mounted on the box body) (refer to the abstract of this document).

[0005] Prior art literature

[0006] Patent Literature

[0007] Patent Document 1: Japanese Patent Application Publication No. 2008-021455 Summary of the invention

[0008] Problems to be solved by the invention

[0009] The method described in Patent Document 1 is a technique for optimizing a position while observing the sensitivity of ions generated by actually flowing a sample solution, but it is not possible to determine whether it is the optimal position before ions are generated, thus causing a decrease in throughput and loss of sample.

[0010] Furthermore, when the capillary is replaced by inserting and removing it, it is also possible that the capillary has a small diameter and may get stuck in the middle (e.g., inside the gas spray tube) during insertion, and may not reach the desired position (e.g., the position where the downstream end of the capillary slightly protrudes from the downstream end of the gas spray tube). If the sample solution is transferred in this state, the inside of the gas spray tube will be flooded, which may cause contamination and device failure.

[0011] The protrusion of the capillary can be visually confirmed to some extent, but the position resolution obtained by visual observation has a limit. A method of configuring a camera, a sensor, etc. to manage the position of the downstream end of the capillary has also been considered, but this will lead to a large-scale and complicated device. In addition, in the ESI ion source, in order to improve the ionization efficiency, the ions and droplets sprayed from the downstream end of the capillary are heated by a heating gas, etc. As a result, the surrounding area of ​​the ion source becomes high temperature, so it is unrealistic to configure a camera or a sensor near it.

[0012] The present invention has been made in view of the above-mentioned problems, and an object of the present invention is to provide an ion source and a control method thereof that can accurately and efficiently determine whether the tip position on the downstream side of a capillary is appropriate.

[0013] Methods for solving problems

[0014] When no sample is introduced into the capillary, the ion source of the present invention measures the current generated by the voltage applied to the capillary by the power supply, and when the above current is within the allowable range, outputs the exposure amount information indicating that the exposure amount of the above capillary is appropriate; when it is not within the allowable range, outputs the above protrusion amount information indicating that the above protrusion amount is inappropriate.

[0015] Effects of the Invention

[0016] According to the ion source of the present invention, whether the tip position of the capillary downstream side is appropriate can be accurately and efficiently determined without reducing the analysis throughput, thereby improving the reproducibility of the tip position of the capillary and achieving high analysis reproducibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a diagram showing the configuration of the mass spectrometer 1 according to the first embodiment.

[0018] Figure 2 It is a flowchart explaining the procedure of replacing the capillary 11.

[0019] Figure 3 This is an example of a combination of a liquid chromatograph (LC) and a mass spectrometer 1 .

[0020] Figure 4 This is a diagram for explaining the timing of replacing the capillary.

[0021] Figure 5 This is an example of a function that determines a replaceable state and an analyzable state.

[0022] Figure 6 A configuration example of a preliminary experiment used to confirm the difference in current value due to the position of the downstream end 12 of the capillary 11 is shown.

[0023] Figure 7 The current meter 34 is used to monitor the fixed Z neb The results are as follows: the value of the current flowing through the counter electrode 26 when the protrusion amount (L) of the capillary 11 is changed.

[0024] Figure 8 It is to describe Z capi This is a graph of current values ​​when the protrusion amount (L) of the capillary 11 is changed at fixed intervals of 1 mm in the range of 5 to 12 mm.

[0025] Fig. 9 Shows that when L is kept constant and Z is changed capi The results of current values ​​are plotted under each condition.

[0026] Fig.10 This is a diagram showing the structure of the ion source 2 according to the second embodiment.

[0027] Fig.11 This is a flowchart illustrating the procedure of replacing the capillary 11 in the second embodiment.

[0028] Fig.12 This is a diagram showing the structure of the ion source 2 according to the third embodiment.

[0029] Fig.13 This is a diagram showing the structure of the ion source 2 according to the fourth embodiment.

[0030] Fig.14 This is a diagram showing the structure of the ion source 2 according to the fifth embodiment.

[0031] Fig.15 This is a diagram showing the structure of the ion source 2 according to the sixth embodiment.

[0032] Fig.16 This is a diagram showing the structure of the ion source 2 according to the seventh embodiment.

[0033] Fig.17 This is a flowchart illustrating the capillary replacement sequence of the eighth embodiment.

[0034] Fig.18 It is explained 3 ≤I≤I 4 Graph of the range.

[0035] Fig.19 This is a flowchart illustrating the capillary replacement sequence of the ninth embodiment.

[0036] Fig. 20 Shows an example of comparing a reference curve with measurement results.

[0037] Fig.21 Shows an example of comparing a reference curve with measurement results.

[0038] Fig. 22Shows an example of comparing a reference curve with measurement results.

[0039] Fig.23 This is a flowchart illustrating the operation procedure of the ion source 2 according to the tenth embodiment.

[0040] Fig.24 This is an example of the result of repeatedly measuring the current value. DETAILED DESCRIPTION

[0041] <Implementation Method 1>

[0042] Figure 1 1 is a block diagram of a mass spectrometer 1 according to Embodiment 1 of the present invention. The mass spectrometer 1 is composed of an ion source 2, a vacuum container 4, etc. The vacuum container 4 has a mass analyzer 3, etc. inside. The ion source 2 is mainly composed of an ion generator 5 and an ion source chamber 6.

[0043] The ions generated by the ion source 2 are introduced into the vacuum container 4 through the hole 8 of the introduction electrode 7 and analyzed by the mass spectrometer 3. Various voltages are applied to the mass spectrometer 3 from the power supply 9. The timing and voltage value of the voltage application of the power supply 9 are controlled by the control unit 10 (calculation unit). In addition, the control unit 10 can also control various parts of the ion source 2 and various parts of the mass spectrometer 1.

[0044] In the ion generating section 5, the sample solution is introduced into the capillary 11, and ions and droplets are sprayed from the downstream end 12 of the capillary 11 by an electric field or the like. The voltage value applied to the capillary 11 is generally about several kV (absolute value). In the case of generating positive ions, a voltage of +several kV is applied to the capillary 11. In the case of generating negative ions, a voltage of -several kV is applied to the capillary 11. The flow rate of the sample solution depends on the inner diameter of the capillary 11, but is generally set in the range of nL / minute to mL / minute. Although it also depends on conditions such as the flow rate of the sample solution, the inner and outer diameters of the capillary 11 are generally set to be less than 1 mm.

[0045] In order to prevent the droplets not introduced into the vacuum container 4, their vaporized components, etc. from leaking out of the device, sometimes the ion source chamber 6 and the vacuum container 4 are in a sealed state (or a nearly sealed state). Furthermore, there may be an exhaust port 13 for exhausting the excess components, etc. In order to observe the spray state of the downstream end 12 of the capillary 11, a window 14 made of a transparent member such as glass may be provided in a part of the ion source chamber 6.

[0046] like Figure 1As shown in FIG. 1 , the interior of the vacuum container 4 is sometimes divided into a plurality of vacuum chambers 15, 16, and 17. Each vacuum chamber is connected to each other through small-diameter holes 18 and 19. The hole 8 of the introduction electrode 7 and these holes 18 and 19 are passages for ions, and voltage can also be applied to the member having each hole. In this case, it is necessary to insulate the vacuum container 4 and other box parts through an insulator (not shown). The number of vacuum chambers is greater than Figure 1 There are also more cases than Figure 1 Few cases.

[0047] The vacuum chambers 15, 16, and 17 are evacuated by vacuum pumps 20, 21, and 22, respectively, and are generally maintained at about several hundred Pa, about several Pa, and about 0.1 Pa or less, respectively. The vacuum chamber 16 is provided with an ion transport unit 23 that allows ions to pass through while converging. As the ion transport unit 23, a multipole electrode, an electrostatic lens, etc. can be used. The ion transport unit 23 is sometimes also arranged in other vacuum chambers such as the vacuum chambers 15 and 17. A high-frequency voltage, a direct current voltage, an alternating current voltage, or a voltage obtained by combining them is applied to the ion transport unit 23 from the power supply 9.

[0048] The mass analysis unit 3 is composed of an ion analysis unit 24, a detector 25, etc. The ion analysis unit 24 separates or dissociates ions. As the ion analysis unit 24, in addition to an ion trap, a quadrupole filter electrode, a collision cell, a time-of-flight mass spectrometer (TOF), etc., a combination of them can also be used. The ions that have passed through the ion analysis unit 24 are detected by the detector 25. As the detector 25, an electron multiplier tube, a multichannel plate (MCP), etc. can be used. The ions detected by the detector 25 are converted into electrical signals, etc., and the control unit 10 uses the electrical signals to analyze the mass, intensity, and other information of the ions in detail. The control unit 10 has an input and output unit, a memory, etc. for accepting instructions from the user, controlling voltages, etc., and also has software required for power supply operation, etc. As the voltage supplied from the power supply 9 to the mass analysis unit 3, in addition to high-frequency voltage, direct current voltage, alternating current voltage, etc., a voltage combined with them can also be used.

[0049] exist Figure 1 In the structure, the counter electrode 26 is arranged in the front section of the introduction electrode 7. By making the gas flow between the introduction electrode 7 and the counter electrode 26 and spraying from the hole 27 of the counter electrode 26, it is possible to suppress the interference components such as excess droplets sprayed from the downstream end 12 of the capillary 11 from entering the hole 8 of the introduction electrode 7. The flow rate of the gas is set to about 0.5 to 10 L / min, and inert gas such as nitrogen or argon is generally used. The diameter of the hole 27 of the counter electrode 26 is usually more than 1 mm, and the applied voltage is usually at most ± several kV.

[0050] exist Figure 1In the configuration, a gas spray tube 28 is arranged around the capillary 11, and the gas is made to flow between the capillary 11 and the gas spray tube 28, and sprayed from the downstream end 29 of the gas spray tube 28, thereby promoting the vaporization of the droplets sprayed from the downstream end 12 of the capillary 11, and improving the ionization efficiency. The gas flow rate is about 0.5 to 10 L / min, and inert gas such as nitrogen or argon is generally used. The inner diameter of the downstream end 29 of the gas spray tube 28 is generally set to be less than 1 mm.

[0051] To further improve ionization efficiency, the space where ions and droplets are sprayed from the downstream end 12 of the capillary 11 may be heated by heating gas (maximum about 800°C) (not shown). The flow rate of the heating gas is about 0.5 to 50 L / min, and inert gas such as nitrogen or argon is generally used.

[0052] The capillary 11 is fixed to the connector 30 via a sealing mechanism (not shown) such as a gasket, an O-ring, or a ferrule. The capillary 11 and the connector 30 may also be integrated by bonding, welding, brazing, or the like. When the gas is allowed to flow between the capillary 11 and the gas spray tube 28, a sealing material 31 for sealing the gas may be provided. Figure 1 In the embodiment, the sealing material is a face seal, but other structures such as a shaft seal may be used as long as airtightness can be maintained. As the sealing material 31, an O-ring, a gasket, a ring made of resin, rubber, etc., etc. can be used.

[0053] The connector 30 has a pipe connection portion 32, and a pipe (not shown) can be connected to the connector 30 via the pipe connection portion 32. The sample is supplied to the capillary 11 by supplying the sample solution to the pipe.

[0054] After the capillary 11 is replaced due to clogging of the capillary 11 or the like (here, the capillary 11 and the connector 30 are fixed to each other), Figure 1 As shown in FIG. 1 , the surfaces of the connector 30 and the gas spray tube 28 are in contact with each other. Therefore, when the device error (device error) of the length of the capillary 11 is small, the position of the downstream end 12 in the Z direction should be reproduced. However, the downstream side of the gas spray tube 28 is often narrowed to increase the speed of the sprayed gas. This may cause the capillary 11 of a very small diameter to get stuck in the middle of the process. Figure 1 The capillary 11 may not reach the fixed position slightly protruding from the downstream end 29 of the gas spray tube 28. If the sample is transported with the downstream end 12 of the capillary 11 remaining inside the gas spray tube 28, the inside of the gas spray tube 28 may be flooded, which may cause contamination or device failure.

[0055] Therefore, in the first embodiment, an ammeter 34 is provided to monitor the current value flowing through the counter electrode 26 when a voltage is applied to the capillary 11 from the power supply 33 after the capillary 11 is replaced. The control unit 10 determines the position of the downstream end 12 of the capillary 11 based on the monitored current value, and determines whether to execute or terminate the analysis based on the result. In the case of termination, an alarm is prompted, for example, through the display 35. As the alarm, various alarms such as a visual monitor, a lamp, a display, an auditory buzzer, and a warning lamp can be used.

[0056] Figure 2 1 is a flowchart for explaining the procedure of replacing the capillary 11. When replacing the capillary 11, after installing a new capillary 11, the current value flowing through the counter electrode 26 is monitored by the ammeter 34. The control unit 10 determines whether the position of the downstream end 12 of the capillary 11 is a normal position based on the measurement result. Based on the determination result, the control unit 10 outputs the protrusion amount information indicating whether the position of the downstream end 12 of the capillary 11 is a normal position. The protrusion amount is determined using the following method. Figure 6 to Figure 9 If it is a normal position, analysis is performed, and if it cannot be determined as a normal position, the control unit 10 outputs an alarm through the display 35.

[0057] In actual pass / fail judgment, a certain range of current values ​​is often considered pass. For example, when the current value (I) measured at the normal position is 30 μA ± 2 μA, the minimum value of the deviation (I 1 )=28μA to maximum value (I 2 )=32μA is considered acceptable, that is, I 1 ≤I≤I 2 The condition is set as the qualified range. This qualified condition is an example, and different conditional expressions can also be used to set a wider range or a narrower range. In the case where it is judged as unqualified and an alarm is issued, the capillary 11 is reinstalled. In the case where it is judged as unqualified even after repeated several times, it can also be judged as an error of the component itself and replaced with a new capillary 11.

[0058] Figure 3 is an example of a combination of a liquid chromatograph (LC) and a mass spectrometer 1. In general, the mass spectrometer 1 is often Figure 3The sample injected into the sample injection part 41 is transported by the pumps 38 and 39, respectively, and is sent to the separation column 42 by the mobile phases 43 and 44 mixed by the mixer 40. The mixing ratio in the mixer 40 can be adjusted by the flow ratio of the pumps 38 and 39. One of the mobile phases 43 and 44 is often water (or a solvent with water as the main component), and the other is often an organic solvent such as methanol or acetonitrile (or a solvent with an organic solvent as the main component). Usually, after the sample is injected into the separation column 42 which has been washed and equilibrated with water, organic solvent, etc. used in the mobile phases 43 and 44, the sample component is eluted from the separation column 42 using the mobile phase 43 or 44 or a solution of the two mobile phases. During elution, by changing the mixing ratio of the mobile phases 43 and 44 over time, the LC peaks of the sample components can be obtained over time (LC separation). Figure 3 As shown, by configuring the ion source 2 downstream of the LC 37, the sample corresponding to the LC peak is ionized at each time, and the ion is analyzed by the mass spectrometer 1. The timing (retention time) of the LC peak corresponding to the sample component can be uniquely defined according to the type of separation column 42, the mixing ratio of the mobile phases 43 and 44, the length of the piping, etc.

[0059] Figure 4 This figure explains the timing of replacing the capillary. Figure 3 In the system, during the process of pumps 38 and 39 delivering liquid to the capillary 11, pressure anomalies due to blockage of the capillary 11, and sensitivity reduction due to degradation of the downstream end 12 of the capillary 11 may occur. In the event of such a phenomenon, the capillary 11 is generally replaced with a new one. In the event of pressure anomalies and sensitivity reduction, the analysis is temporarily stopped, and the delivery of liquid, gas, and power are stopped (at this time, the vacuum pumps 20, 21, and 22 are usually not stopped). Afterwards, if the pressure of the pumps 38 and 39 and the temperature of the ion source 2 drop sufficiently to allow the capillary 11 to be replaced, the capillary 11 is implemented. Figure 2 If the replacement process is completed, liquid delivery, gas delivery, power supply, etc. are started. If the pressure of pumps 38 and 39 and the temperature of ion source 2 are sufficiently stable and become analyzable, analysis is started.

[0060] Figure 5 This is an example of a function for determining a replaceable state and an analyzable state. For example, a pressure gauge 45 for monitoring the pressure of LC 37 and a temperature adjustment unit 46 for monitoring the temperature of the ion source 2 may be provided. In addition, various interlock functions may be provided in power supplies, device covers (not shown), and the like.

[0061] Figure 6The following is a configuration example of a preliminary experiment used to confirm the difference in current value caused by the position of the downstream end 12 of the capillary 11. Figure 1 This configuration has a function for adjusting the relative position (Z) of the downstream end 29 of the gas spray tube 28 relative to the center of the hole 27 of the counter electrode 26 in the Z direction. neb ) and a driving unit 47 for changing the relative position (Z) of the downstream end 12 of the capillary 11 in the Z direction. capi ) The driving unit 48 changes. Since the relative positions of the capillary 11 and the gas spray tube 28 in the Z direction change, in this configuration, the seal material 31 is a shaft seal. The diameter of the hole 27 of the counter electrode 26 is 4 mm.

[0062] exist Figure 6 In the embodiment, the downstream end 12 of the capillary 11 protrudes relative to the space in the ion source chamber 6. The protrusion amount can be defined as the length of the portion of the capillary 11 not covered by the gas spray tube 28 (the portion of length L) exposed relative to the space in the ion source chamber 6, or it can be defined as the length of the capillary 11 itself protruding from the inner wall of the ion source chamber 6. Regardless of which definition is used, it can be determined whether the position of the downstream end 12 of the capillary 11 is appropriate by determining whether the protrusion amount is appropriate. Figure 7 to Figure 9 The results of verifying this situation are described.

[0063] Figure 7 The current meter 34 is used to monitor the fixed Z neb The results are as follows: the current value flowing through the counter electrode 26 when the protrusion amount (L) of the capillary 11 is changed. Here, the distance (X) between the counter electrode 26 and the center of the capillary 11 is set to 5 mm, and 5 kV is applied to the capillary 11 and the gas spray tube 28 from the power supply 33. Figure 7 In the neb The current values ​​when the protrusion amount (L) of the capillary 11 is changed are plotted at fixed intervals of 1 mm in the range of 5 to 15 mm. Figure 1 As shown, Z neb The fixing of Z is based on the premise that the position of the gas spray tube 28 is restricted by the box part such as the ion source chamber 6. neb By changing L, (a) the length of the portion of the capillary 11 not covered by the gas spray tube 28 (the portion having a length of L) exposed relative to the space in the ion source chamber 6 changes, and (b) the length of the capillary 11 itself protruding from the inner wall of the ion source chamber 6 changes. In other words, the protrusion amount of the capillary 11 relative to the space in the ion source chamber 6 changes.

[0064] No matter which Z nebUnder the conditions of , the difference in current value caused by L is significant. This teaches that it is possible to judge whether the position of the downstream end 12 of the capillary 11 is in a normal position based on the current value. Therefore, by using the length L of the portion of the capillary 11 not covered by the gas spray tube 28 (the portion with a length of L) exposed relative to the space in the ion source chamber 6, or by using the length of the capillary 11 itself protruding from the inner wall of the ion source chamber 6, it is possible to judge whether the position of the downstream end 12 is in a normal position.

[0065] Figure 8 Is Z capi A graph of the current value when the protrusion amount (L) of the capillary 11 is changed at fixed intervals of 1 mm in the range of 5 to 12 mm is plotted. capi Fixed and Figure 1 Different from the above, the position of the capillary 11 is limited by the ion source chamber 6 and other box parts. capi By changing L, the length of the portion of the capillary 11 not covered by the gas spray tube 28 (the portion of length L) exposed to the space in the ion source chamber 6 changes. That is, the amount of protrusion of the capillary 11 relative to the space in the ion source chamber 6 changes.

[0066] No matter which Z capi Under the conditions of , the difference in current value caused by L is significant. This teaches that it is possible to judge whether the position of the downstream end 12 of the capillary 11 is in a normal position based on the current value. Therefore, by using the length L of the portion of the capillary 11 not covered by the gas spray tube 28 (the portion with a length L) exposed relative to the space in the ion source chamber 6, it is possible to judge whether the position of the downstream end 12 is in a normal position.

[0067] Fig. 9 Shows that when L is kept constant and Z is changed capi The results of the current value are plotted under each condition. By fixing L and making Z capi The length of the capillary 11 protruding from the inner wall of the ion source chamber 6 will change. That is, the protrusion amount of the capillary 11 relative to the space in the ion source chamber 6 will change. Fig. 9 The results shown show that whether the position of the downstream end 12 is in the normal position can be determined by the protruding length of the capillary 11 itself from the inner wall of the ion source chamber 6 .

[0068] according to Figure 7 to Figure 9 The verification results show that, although the relative position (X) between the downstream end 12 of the capillary 11 and the counter electrode 26 is constant, the amount of the capillary 11 protruding relative to the space in the ion source chamber 6 depends largely on the current value. Therefore, using the current value, it is possible to determine whether the position of the capillary 11 is appropriate.

[0069] <Implementation 1: Summary>

[0070] In the ion source 2 of the first embodiment, when no sample is supplied to the capillary 11, the current flowing due to the voltage applied to the capillary 11 by the power supply 33 is measured by the ammeter 34, and the control unit 10 determines whether the capillary 11 is in the normal position based on the measurement result. Thus, before the mass spectrometer 1 starts analyzing ions, it is possible to confirm whether the capillary is in the normal position, thereby preventing problems caused by contamination, device failure, etc., and ensuring high analysis stability.

[0071] <Implementation Method 2>

[0072] Fig.10 2 is a diagram showing the configuration of the ion source 2 according to the second embodiment of the present invention. In the second embodiment, a configuration for adjusting the position of the capillary 11 based on the current measurement result will be described. For the sake of convenience, the differences from the first embodiment will be mainly described.

[0073] Fig.10 The ion source 2 includes a drive unit 48 for adjusting the Z-direction position of the capillary 11 relative to the gas spray tube 28. Since the relative position of the capillary 11 and the gas spray tube 28 in the Z-direction changes, the seal member 31 is a shaft seal in this configuration.

[0074] Fig.11 1 is a flowchart illustrating the sequence of replacing the capillary 11 in the second embodiment. When replacing the capillary 11, after setting a new capillary 11, the current value flowing through the counter electrode 26 is monitored by the ammeter 34. The control unit 10 determines whether the position of the downstream end 12 of the capillary 11 is in a normal position based on the measurement result. If it is in a normal position, the analysis is performed. If it cannot be determined to be in a normal position, if the number of current measurements (n) is the first time, the position of the downstream end 12 of the capillary 11 in the Z direction is adjusted by the drive unit 48. In the position adjustment, for example, based on Figure 7 The current value of the measured result is used to determine the current position, and adjustments are made to correct the difference between the position and the normal position. This adjustment can be automatic or manual. After the position adjustment, the current is measured again, and the Figure 2 Similarly, if in I 1 ≤I≤I 2 If the re-measurement fails, since n = 2, it is considered to be an error in the component itself, and the analysis is started. Figure 2 Similarly, an alarm is issued, and measures such as replacing the capillary tube 11 with a new one can be taken. The threshold value n of the number of measurements may be set to a value other than n=2.

[0075] According to the ion source 2 of the second embodiment, even if the attachment position of the capillary 11 is not optimal, the position can be adjusted without removing the capillary 11. Thus, the flux loss due to replacement of the capillary 11 can be minimized.

[0076] <Implementation Method 3>

[0077] Fig.12 1 is a diagram showing the configuration of the ion source 2 according to the third embodiment of the present invention. In the third embodiment, a configuration for adjusting the position of the gas spray tube 28 based on the current measurement result will be described. For the sake of convenience, the differences from the first embodiment will be mainly described.

[0078] Fig.12 The ion source 2 is provided with a driving unit 47 for adjusting the Z-direction position of the gas spray tube 28 relative to the capillary 11. Since the relative position between the capillary 11 and the gas spray tube 28 in the Z-direction changes, in this configuration, the sealing material 31 is configured as a shaft seal. Since the position of the capillary 11 is used as a reference, the positions of the capillary 11 and the connector 30 are restricted by components (not shown) and the like to the housing portion of the ion source chamber 6. The order of replacing the capillary 11 is the same as Fig.11 They are roughly the same, so the description is omitted.

[0079] The ion source 2 of the present embodiment 3 is also similar to the embodiment 2. Even if the installation position of the capillary 11 is not optimal, the position can be adjusted without removing the capillary 11. Thus, the flux loss caused by replacing the capillary 11 can be minimized. The drive unit 47 described in the embodiment 2 and the drive unit 48 described in the embodiment 3 can also be adjusted as described in the embodiment 2. Figure 6 Use them together like that.

[0080] <Implementation Method 4>

[0081] Fig.13 1 is a diagram showing the structure of the ion source 2 according to the fourth embodiment of the present invention. In the fourth embodiment, an ion source is described which determines the downstream end position of the capillary 11 based on the current value of the introduction electrode 7. For the sake of convenience, the differences from the first embodiment are mainly described.

[0082] exist Fig.13 In the embodiment 1 to 3, there is no counter electrode 26. Under the condition that the flow rate of the sample solution is small, there is a case where the counter electrode 26 is not required and the gas spray is performed from the inside of the counter electrode 26. This structure can be applied to this case. In this structure, since there is no counter electrode 26, the ammeter 34 measures the current value flowing in the introduction electrode 7. The other structures and sequences are the same as those of the embodiments 1 to 3, and the same effects can be obtained.

[0083] <Implementation method 5>

[0084] Fig.14 1 is a diagram showing the configuration of an ion source 2 according to a fifth embodiment of the present invention. The ion source 2 according to the fifth embodiment does not include a gas spray tube 28. For ease of description, the differences from the first embodiment will be mainly described.

[0085] Under the condition that the flow rate of the sample solution is small, there is a case where the gas spray tube 28 is not required and the gas spray is performed from the inside of the gas spray tube 28. Since there is no gas spray tube 28, in this embodiment 5, the capillary 11 and the connector 30 are provided in the adapter member 49, etc. The other structures and procedures are the same as those of the embodiments 1 to 4, and the same effects can be obtained.

[0086] <Implementation Method 6>

[0087] Fig.15 1 is a diagram showing the configuration of the ion source 2 according to the sixth embodiment of the present invention. In the sixth embodiment, a configuration for determining the downstream end position of the capillary 11 based on the current value of the deflection electrode will be described. For ease of description, the differences from the first embodiment will be mainly described.

[0088] Fig.15 In addition to the structure described in Embodiment 1, the structure further includes a deflection electrode 50. If interfering components such as droplets flow in from the introduction electrode 7, it will cause contamination of various electrodes inside the vacuum container 4, resulting in reduced sensitivity. Furthermore, the life of the detector 25 can also be extended. By using a reverse gas spray from the inside of the opposing electrode 26, it is possible to prevent the inflow of interference to a certain extent, but when this is still insufficient, it is sometimes necessary to keep the downstream end 12 of the capillary 11, which is the spray port for ions and droplets, away from it. By keeping the downstream end 12 away, the inflow of interference is reduced, but the inflow of ions is also reduced, resulting in reduced sensitivity. In order to compensate for this reduced sensitivity, a deflection electrode 50 is sometimes arranged in the ion source chamber 6. By applying a maximum voltage of about ±several kV to the deflection electrode 50, the ions are forcibly deflected in the direction of the introduction electrode 7, thereby improving the ion introduction efficiency.

[0089] When the capillary 11 is separated from the introduction electrode 7 and the current value in the counter electrode 26 and the introduction electrode 7 is measured, the current may not be detected smoothly due to the distance between the two. In this case, by monitoring the current value flowing through the deflection electrode 50 that can be arranged closer, the same effect as measuring the current value in the counter electrode 26 and the introduction electrode 7 can be obtained. The other configurations and procedures are the same as those in Embodiments 1 to 5.

[0090] <Implementation Method 7>

[0091] Fig.16 1 is a block diagram of the ion source 2 according to Embodiment 7 of the present invention. Embodiment 7 describes a structure for determining the downstream end position of the capillary 11 based on the current value of the current measurement electrode. For ease of description, mainly the differences from Embodiment 1 are described.

[0092] Fig.16 In addition to the structure described in Embodiment 1, the structure further includes a dedicated electrode 51 for current measurement. Since pollutants such as droplets are also sprayed from the downstream end 12 of the capillary 11 together with ions, there is a possibility that the surfaces of the counter electrode 26, the introduction electrode 7, the deflection electrode 50, etc. are contaminated. The mass spectrometer 1 uses a vacuum to introduce ions from the hole 8 of the introduction electrode 7, so even if some dirt adheres to these electrodes, the ions are introduced by the force of the airflow, and the sensitivity reduction rate is small. However, when measuring the current of these electrodes, there is a concern about changes in the electric field due to contamination. Therefore, in this embodiment 7, a dedicated electrode 51 for current measurement dedicated to current monitoring is configured. If the dedicated electrode 51 for current measurement is not located closer to the downstream end 12 of the capillary 11 than other electrodes, the discharge current will flow into other electrodes, but on the contrary, if the dedicated electrode 51 for current measurement is too close to the downstream end 12, the electric field will be disturbed, reducing the ionization efficiency. Therefore, it is preferred that, as Fig.16 By configuring the driving unit 52 in this manner, during analysis, the current measurement dedicated electrode 51 can be moved to a position that does not hinder the electric field and is not exposed to contamination during analysis.

[0093] According to the ion source 2 of the seventh embodiment, the reliability of the current measurement result due to contamination can be improved, so the accuracy of determining whether the downstream end 12 is in the normal position can be improved. Furthermore, the influence of the current measurement electrode 51 on the analysis can be alleviated.

[0094] <Implementation Method 8>

[0095] Fig.17 This is a flowchart for explaining the capillary replacement sequence of the eighth embodiment of the present invention. In the eighth embodiment, an example of an operation of adjusting the capillary voltage based on the current measurement result to implement the analysis process is described. The configuration of the ion source 2 and the mass spectrometer 1 is the same as that of the first to seventh embodiments. In the following, for the sake of convenience, the configuration of the ion source 2 of the first embodiment is taken as a premise, but this flowchart can also be used in the ion source 2 of other embodiments.

[0096] When the capillary 11 is replaced, after a new capillary 11 is installed, the current value flowing through the counter electrode 26 is monitored by the ammeter 34. Figure 2 Similarly, if the test result is I 1 ≤I≤I 2Even in the case of failure, if the same electric field (sensitivity) range (I 3 ≤I≤I 4 ), do not adjust the position or replace it, but adjust the voltage in the original state, measure the current value again, and if it is qualified, start the analysis under the condition of correcting the voltage. 3 ≤I≤I 4 If the current re-measurement fails, it is determined that the component itself is faulty, an alarm is issued, and measures such as replacing the capillary 11 with a new one can be taken. 1 ≤I≤I 2 ,I 3 ≤I≤I 4 The qualification condition is just one example, and different conditional expressions may be used to set a wider range or a narrower range.

[0097] Fig.18 It is explained 3 ≤I≤I 4 Graph of the range. Fig.18 It will be Figure 6 In the structure of X=3mm, Z neb =25mm and the result of changing L and voltage value. A capillary with an outer diameter of 0.27mm for the capillary 11 and an inner diameter of 0.4mm for the front end of the gas spray tube 28 is used. In this configuration, the optimal conditions are assumed to be 5.5kV for the applied voltage to the capillary 11 and L=0.7mm (about 30μA). The application range of the power supply 33 used in this experiment is up to 5.8kV, so the range that can reach 30μA under the condition of L=0.1mm increment is the range of L=0.6~0.9mm. That is, in the configuration of this L, it is believed that it can be adjusted to 30μA by voltage adjustment. For example, in the initial current measurement, if a result of 40μA appears under an applied voltage of 5.5kV, it can be inferred that L=0.9mm. In this case, by reducing the voltage to 5.3kV, it is possible to adjust the electric field to a current of about 30μA.

[0098] Taking the case where the optimum voltage in actual analysis is 4 kV as an example, the correction applied voltage during analysis is explained. Fig.18When the correlation between the horizontal axis and the vertical axis shows the same tendency as the correlation between the applied voltage and the ion intensity during analysis, in the above example, since the voltage is adjusted from 5.5 kV to 5.3 kV, the correction voltage during analysis is set to 3.855 kV according to the relationship of the ratio, thereby obtaining the same ion intensity as the condition of L = 0.7 mm and 4 kV. The conversion formula related to this correction is also affected by other analysis conditions, so it is not limited to this example.

[0099] By the capillary replacement sequence of this embodiment 8, even if the installation position of the capillary 11 is not optimal, the position can be adjusted without removing the capillary 11, so that the flux loss caused by the replacement can be minimized. The voltage adjustment method in this embodiment 8 can also be used in conjunction with the position adjustment method of the downstream end 12 in other embodiments.

[0100] <Implementation Method 9>

[0101] Fig.19 1 is a flowchart for explaining the capillary replacement procedure of Embodiment 9 of the present invention. In Embodiment 9, by comparing the curves of current values ​​obtained by applying multiple voltages to the capillary 11 with the reference curve, it is determined whether the position of the downstream end 12 is qualified. The configuration of the ion source 2 and the mass spectrometer 1 is the same as that of Embodiments 1 to 8.

[0102] Figure 20 to Figure 22 An example of comparing the reference curve with the measurement result is shown. If different voltages are applied to the capillary 11, Figure 20 to Figure 22 The control unit 10 uses the solid line as a reference curve. Fig. 20 In the case of , the threshold voltage value at which current measurement can be performed (the threshold voltage at which the current value rises) is different between the reference curve and the actual measurement result. Fig.21 In the case of , the slope of the current value with respect to the applied voltage is different between the reference curve and the measured result. Fig. 22 In the example, the current value for the same applied voltage is different between the reference curve and the actual measurement result. The control unit 10 pre-sets an allowable range for each error between the reference curve and the actual measurement result. If it is within the allowable range, it is determined to be qualified, and if it is outside the allowable range, it is determined to be unqualified. In the determination, other indicators may also be used.

[0103] According to the capillary replacement sequence of the present embodiment 9, the determination based on the current value is more accurate than when a single voltage is applied to the capillary 11. The method of comparing the reference curve of the present embodiment 9 with the actual measurement result can also be applied to Fig.11 , Fig.17 capillary replacement procedure.

[0104] <Implementation Method 10>

[0105] Fig.23 1 is a flowchart illustrating the operation sequence of the ion source 2 of the embodiment 10 of the present invention. The ion source 2 of the embodiment 10 measures the current value when the analysis is paused. In judging whether the result of the current value measurement is qualified or not, the methods of the above-mentioned embodiments can be used. If qualified, the next analysis is carried out. If unqualified, the capillary 11 is replaced, the position is adjusted, and the voltage is adjusted. The methods of the various embodiments can also be combined.

[0106] Fig.24 This is an example of the result of repeatedly measuring the current value. If the current value is repeatedly measured, the following is obtained: Fig.24 The error curve of the vertical axis can be, for example, Figure 20 to Figure 22 The control unit 10 can determine that the component is defective when the cumulative value of the error becomes greater than a threshold value. This enables predictive diagnosis of component degradation and life.

[0107] <Variations of the present invention>

[0108] The present invention is not limited to the above-mentioned embodiments, and includes various modified examples. For example, the above-mentioned embodiments are described in detail in order to explain the present invention in an easy-to-understand manner, and are not limited to all the structures described. In addition, a part of the structure of a certain embodiment can be replaced with the structure of other embodiments, and in addition, the structure of other embodiments can be added to the structure of a certain embodiment. In addition, for a part of the structure of each embodiment, other structures can be added, deleted, or replaced. In addition, since voltage is applied to the various electrodes used in each embodiment, when installed in a box part, etc., they are sometimes installed via an insulating member, but for simplicity, the insulating material is not shown in the figures.

[0109] In the above embodiment, the current flowing through each electrode when the power source 9 applies a voltage to the capillary 11 is measured by the ammeter 34, but the ammeter 34 may directly or indirectly measure the current flowing through the capillary 11. Even in this case, the same effect as in the above embodiment can be achieved. That is, it is sufficient as long as the current generated by the power source 9 applying a voltage to the capillary 11 when the sample is not supplied to the capillary 11 can be measured.

[0110] In the above embodiment, the control unit 10 can output the protrusion amount information in any form. For example, the protrusion amount can be presented to the user via a display, etc. Alternatively, for example, data describing the protrusion amount can be output to other computing devices, etc. Other appropriate output forms can also be used.

[0111] In the above embodiments, the control unit 10 may be configured using hardware such as a circuit device having the above functions, or may be configured by a computing device such as a CPU (Central Processing Unit) executing software having the above functions.

[0112] Explanation of symbols

[0113] 1: mass spectrometer, 2: ion source, 3: mass analysis unit, 4: vacuum container, 5: ion generation unit, 6: ion source chamber, 7: introduction electrode, 8: hole, 9: power supply, 10: control unit, 11: capillary, 12: downstream end, 13: exhaust port, 14: window, 15-17: vacuum chamber, 18-19: hole, 20-22: vacuum pump, 23: ion transport unit, 24: ion analysis unit, 25: detector, 26: counter electrode, 27: hole, 28: gas spray tube, 29 : Downstream end, 30: Connector, 31: Sealing material, 32: Piping connection part, 33: Power supply, 34: Ammeter, 35: Display, 37: Liquid chromatograph (LC), 38~39: Pump, 40: Mixer, 41: Sample injection part, 42: Separation column, 43~44: Mobile phase, 45: Pressure gauge, 46: Temperature regulating part, 47: Drive part, 48: Drive part, 49: Connector component, 50: Deflection electrode, 51: Current measurement dedicated electrode, 52: Drive part.

Claims

1. An ion source control method, characterized in that: It is a method of controlling the ion source that ionizes the sample. The ion source comprises: a capillary tube through which a solution containing the sample passes, an ion source chamber housing the tip portion of the capillary, a power source that applies a voltage to the capillary, an ammeter for measuring a current generated by the voltage applied by the power source to the capillary when the sample is not introduced into the capillary, a gas spray tube which accommodates at least a portion of the capillary tube and sprays a gas for vaporizing a substance sprayed from the capillary tube, a second driving unit that adjusts the protrusion amount described below by moving the gas spray tube; The ion source control method includes the step of outputting protrusion amount information indicating whether the protrusion amount of the front end portion of the capillary relative to the space in the ion source chamber is appropriate, In the step of outputting the protrusion amount information, when the current measured by the ammeter is within an allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output, and when it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output, The ion source control method further comprises: When the current measured by the ammeter is not within the allowable range, the second driving unit is used to move the gas spray tube to adjust the protrusion amount. After adjusting the protrusion amount, if the current measured by the ammeter is within the allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output; if it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output.

2. An ion source control method, characterized in that: It is a method of controlling the ion source that ionizes the sample. The ion source comprises: a capillary tube through which a solution containing the sample passes, an ion source chamber housing the tip portion of the capillary, a power source that applies a voltage to the capillary, an ammeter for measuring a current generated by the voltage applied by the power source to the capillary when the sample is not introduced into the capillary, an introduction electrode having an introduction hole for introducing the ions into an analysis device for analyzing the ions contained in the sample ejected from the capillary, a counter electrode disposed between the introduction electrode and the capillary and having a second introduction hole communicating with the introduction hole, a gas introduction port for introducing gas into a space between the introduction electrode and the counter electrode so that the gas is ejected from the second introduction hole; The ion source control method includes the step of outputting protrusion amount information indicating whether the protrusion amount of the front end portion of the capillary relative to the space in the ion source chamber is appropriate, In the step of outputting the protrusion amount information, when the current measured by the ammeter is within an allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output, and when it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output, In the step of outputting the protrusion amount information, a result of measuring a current flowing through the counter electrode by the ammeter is obtained as a current generated by applying a voltage to the capillary by the power supply.

3. An ion source control method, characterized in that: It is a method of controlling the ion source that ionizes the sample. The ion source comprises: a capillary tube through which a solution containing the sample passes, an ion source chamber housing the tip portion of the capillary, a power source that applies a voltage to the capillary, an ammeter for measuring a current generated by the voltage applied by the power source to the capillary when the sample is not introduced into the capillary, an introduction electrode having an introduction hole for introducing the ions into an analysis device for analyzing the ions contained in the sample ejected from the capillary; The ion source control method includes the step of outputting protrusion amount information indicating whether the protrusion amount of the front end portion of the capillary relative to the space in the ion source chamber is appropriate, In the step of outputting the protrusion amount information, when the current measured by the ammeter is within an allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output, and when it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output, In the step of outputting the protrusion amount information, a result of measuring a current flowing through the introduction electrode by the ammeter is obtained as a current generated by applying a voltage to the capillary by the power supply.

4. An ion source control method, characterized in that: It is a method of controlling the ion source that ionizes the sample. The ion source comprises: a capillary tube through which a solution containing the sample passes, an ion source chamber housing the tip portion of the capillary, a power source that applies a voltage to the capillary, an ammeter for measuring a current generated by the voltage applied by the power source to the capillary when the sample is not introduced into the capillary, an introduction electrode having an introduction hole for introducing the ions into an analysis device for analyzing the ions contained in the sample ejected from the capillary, a deflection electrode for deflecting the ions toward the introduction electrode; The ion source control method includes the step of outputting protrusion amount information indicating whether the protrusion amount of the front end portion of the capillary relative to the space in the ion source chamber is appropriate, In the step of outputting the protrusion amount information, when the current measured by the ammeter is within an allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output, and when it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output, In the step of outputting the protrusion amount information, a result of measuring a current flowing through the deflection electrode by the ammeter is obtained as a current generated by applying a voltage to the capillary by the power supply.

5. An ion source control method, characterized in that: It is a method of controlling the ion source that ionizes the sample. The ion source comprises: a capillary tube through which a solution containing the sample passes, an ion source chamber housing the tip portion of the capillary, a power source that applies a voltage to the capillary, an ammeter for measuring a current generated by the voltage applied by the power source to the capillary when the sample is not introduced into the capillary, an electric current measuring electrode capable of adjusting a relative position with respect to the front end portion of the capillary; The ion source control method includes the step of outputting protrusion amount information indicating whether the protrusion amount of the front end portion of the capillary relative to the space in the ion source chamber is appropriate, In the step of outputting the protrusion amount information, when the current measured by the ammeter is within an allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output, and when it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output, In the step of outputting the protrusion amount information, a result of measuring a current flowing through the current measuring electrode by the ammeter is obtained as a current generated by applying a voltage to the capillary by the power supply, The ion source control method further comprises: a step of obtaining a result of measuring a current flowing through the current measuring electrode by the ammeter after the current measuring electrode is moved to a first position when the sample is not introduced into the capillary; The step of moving the current measuring electrode to a second position farther from the tip of the capillary than the first position when the sample is introduced into the capillary.

6. An ion source control method, characterized in that: It is a method of controlling the ion source that ionizes the sample. The ion source comprises: a capillary tube through which a solution containing the sample passes, an ion source chamber housing the tip portion of the capillary, a power source that applies a voltage to the capillary, an ammeter for measuring a current generated by the voltage applied by the power source to the capillary when the sample is not introduced into the capillary; The ion source control method includes the step of outputting protrusion amount information indicating whether the protrusion amount of the front end portion of the capillary relative to the space in the ion source chamber is appropriate, In the step of outputting the protrusion amount information, when the current measured by the ammeter is within an allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output, and when it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output, The ion source control method further comprises: When the current measured by the ammeter is not within the allowable range but within a second allowable range, changing the voltage applied to the capillary by the power supply, After changing the voltage applied by the power supply to the capillary, when the current measured by the ammeter is within the allowable range, controlling the power supply to apply the changed voltage to the capillary, and when it is not within the allowable range, outputting the protrusion amount information indicating that the protrusion amount is inappropriate.

7. The ion source control method according to claim 6, characterized in that: The ion source control method further includes the step of outputting the protrusion amount information indicating that the protrusion amount is inappropriate, when the current measured by the ammeter is not within the allowable range and is not within the second allowable range.

8. An ion source control method, characterized in that: It is a method of controlling the ion source that ionizes the sample. The ion source comprises: a capillary tube through which a solution containing the sample passes, an ion source chamber housing the tip portion of the capillary, a power source that applies a voltage to the capillary, an ammeter for measuring a current generated by the voltage applied by the power source to the capillary when the sample is not introduced into the capillary, a storage unit storing correspondence data acquired by measuring in advance the correspondence between the voltage applied by the power supply to the capillary and the current measured by the ammeter; The ion source control method includes the step of outputting protrusion amount information indicating whether the protrusion amount of the front end portion of the capillary relative to the space in the ion source chamber is appropriate, In the step of outputting the protrusion amount information, when the current measured by the ammeter is within an allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output, and when it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output, The ion source control method also includes the following steps, namely, when the error between the measured data obtained by measuring the correspondence between the voltage applied by the power supply to the capillary and the current measured by the ammeter and the correspondence data is within a third allowable range, outputting the protrusion amount information indicating that the protrusion amount is appropriate; when it is not within the third allowable range, outputting the protrusion amount information indicating that the protrusion amount is inappropriate.

9. The ion source control method according to claim 8, characterized in that: As the error, the phase difference between the measured data and the corresponding relationship data is obtained for any of the following: The current meter measures the threshold voltage at which the current starts to rise from 0. The slope of the current measured by the ammeter with respect to the voltage applied by the power supply to the capillary corresponds to the current measured by the ammeter at the same voltage value applied by the power supply to the capillary.

10. The ion source control method according to any one of claims 1 to 9, characterized in that: The ion source further includes a first driving unit that adjusts the protrusion amount by moving the capillary. The ion source control method further comprises: When the current measured by the ammeter is not within the allowable range, the capillary is moved by the first driving unit to adjust the protrusion amount. After adjusting the protrusion amount, if the current measured by the ammeter is within the allowable range, the protrusion amount information indicating that the protrusion amount is appropriate is output; if it is not within the allowable range, the protrusion amount information indicating that the protrusion amount is inappropriate is output.

11. An ion source, characterized in that: It is an ion source for ionizing the sample, and has: a capillary tube through which a solution containing the sample passes, an ion source chamber housing the tip portion of the capillary, a power source that applies a voltage to the capillary, an ammeter for measuring a current generated by the voltage applied by the power source to the capillary when the sample is not introduced into the capillary, A calculation unit that performs control in the ion source control method according to any one of claims 1 to 10.

12. A mass spectrometer, characterized in that: A device comprising the ion source according to claim 11.

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