JP4212629B2 - Mass spectrometer - Google Patents

Description

  The present invention relates to a mass spectrometer that analyzes substances (samples) having various chemical properties that exist as a mixture in a liquid phase, and in particular, a quadrupole ion trap type mass spectrometer is provided in the mass spectrometer. The present invention relates to a mass spectrometer that can be used to analyze a sample at a time.

  Currently, in the field of analysis, establishment of analysis techniques for mixtures is required. For example, when analyzing harmful substances in the environment, various substances are contained in the collected sample (for example, lake water). The same applies to the analysis of biological materials. Furthermore, various substances are contained in biological samples such as blood and urine. Thus, in order to analyze environment-related substances and biological substances, a technique capable of handling a mixture is essential, and a mass spectrometer capable of analyzing such a mixture sample at one time is required.

  However, it is generally difficult to analyze the above mixture directly. For this reason, after going through the process of separating the mixture, each component is detected, and thus each component of the mixture is identified. In such a situation, a so-called liquid chromatograph / mass spectrometer (an apparatus that combines a liquid chromatograph excellent in separating a mixture into components and a mass spectrometer excellent in substance identification) (Hereinafter referred to as LC / MS) is very effective for the analysis of a mixture sample which is the above-mentioned environment or biological substance.

Conventionally, a mass spectrometer that ionizes a sample using an electrostatic spraying method or the like, and analyzes a newly generated sample ion by a so-called mass analyzer called an ion trap type mass analyzer is, for example, the following non- It is disclosed in Patent Document 1. The operation principle of the ion trap mass spectrometer is already disclosed in, for example, Patent Document 1 below.

  On the other hand, using a liquid chromatograph / mass spectrometer to analyze a sample such as an organic substance with high sensitivity in one analysis is already known, for example, from Patent Document 2 below.

U.S. Pat. No. 4,540,884 JP 05-275053 A "LC / API Mass Spectrometry Method" Analytical Chemistry, 1991, 63, 375

  By the way, in such an analyzer, the efficiency (ionization efficiency) of conversion into positive ions or negative ions in the ion source differs depending on the mixture sample to be measured. For example, acidic peptides tend to generate negative ions, and basic peptides tend to generate positive ions. Therefore, in order to analyze acidic peptides, it is possible to perform analysis with high sensitivity by setting the operation of the mass spectrometer to the negative ion detection mode and to analyze the basic peptides in the positive ion detection mode. it can.

  However, in the above-described conventional LC / MS, the polarity of ions to be detected must be determined prior to analysis. Therefore, when analyzing an unknown substance, an operator must first determine whether the ion is positive or negative. If the detection by one polarity of negative ions was attempted and satisfactory results could not be obtained, a double effort was required to try the opposite polarity again.

  On the other hand, a method for analyzing positive ions and negative ions of a sample by one measurement operation is described in the above-mentioned Japanese Patent Application Laid-Open No. 05-275053. However, in this prior art, mass spectrometry is performed. As the unit, a magnetic field type or quadrupole type mass spectrometer is used. Therefore, this conventional technique has the following problems.

  That is, in a magnetic field type or a quadrupole type mass analysis unit, it generally takes 4 to 5 seconds to acquire one mass spectrum, although it depends on the mass range to be analyzed and the required mass resolution. Therefore, if the analyzer performs positive ion measurement and negative ion measurement one by one, it takes at least about 10 seconds. Therefore, if the time width sent from the liquid chromatograph of the sample is sufficient (for example, about several minutes), there is a problem with the above-described conventional analysis method and apparatus that measure every 10 seconds. There was no.

  However, in particular, in the analysis of environment-related substances and biological substances described above, the time width during which the sample to be mass analyzed from the liquid chromatograph that separates the mixture varies depending on the separation conditions, etc. Often within minutes. Therefore, in the case of such a sample, when performing quantitative analysis using the mass chromatogram obtained by mass spectrometry, there were too few measurement points, and the subject that measurement accuracy fell would arise. Such a problem is conspicuous in a mass spectrometer equipped with an LC that performs high-speed separation of a liquid phase sample, such as capillary electrophoresis. Therefore, the mass spectrometry described in the above Japanese Patent Laid-Open No. 05-275053 There is a problem that the method and apparatus are not necessarily suitable for a mass spectrometer capable of measuring a sample at high speed.

  Therefore, in the present invention, in view of the above problems in the prior art, even when a liquid chromatograph (LC) capable of separating a sample at a high speed as described above is used, the measurement accuracy does not decrease. Another object of the present invention is to provide a mass spectrometer capable of measuring a mixture sample having various chemical properties including environment-related substances and biological-related substances at high speed while reducing the labor of an operator.

  According to the present invention, in order to achieve the above object, first, a mass spectrometer that analyzes a sample introduced after being separated in a separation unit that separates a mixture sample in a liquid phase, the separation is separated in the separation unit. An ionization means for ionizing the sample, an ion introduction pore for taking ions related to the sample generated by the ionization means into a vacuum, and an analysis for analyzing the ions introduced from the ion introduction pore In addition to the mass analyzer, the mass analyzer is constituted by an ion trap mass analyzer that performs ion trap mass analysis, and the sample introduced from the separation unit is further converted to the ion trap type. A mass spectrometer provided with means for specifying by a series of measurement operations of positive ion measurement and negative ion measurement is provided by the mass analyzer.

  According to the present invention, in the mass spectrometer, the ion trap type mass analyzer includes an electrode that forms a space for confining the ions introduced from the ion introduction pores. According to the present invention, the separation unit for introducing the sample separated into the ionization means is a high-speed separation means having a time width of 1 minute or less for separating and sending the mixture sample to be analyzed in the liquid phase. For example, separation means by liquid chromatography or capillary electrophoresis.

  According to the present invention, in order to achieve the above-mentioned object, in addition to the above-mentioned invention, a mass spectrometer for analyzing a mixture sample introduced after being separated, the ionization for ionizing the separated sample Means, an ion introduction pore for taking in the ions related to the sample generated by the ionization means into a vacuum, and a mass analyzer for analyzing the ions introduced from the ion introduction pore In addition, in the first part of the measurement operation by the mass analyzer, a control device is provided that performs positive ion measurement and negative ion measurement, and sets the polarity of the subsequent measurement operation based on the measurement result. A mass spectrometer is provided.

  And according to the present invention, the control device performs the measurement of positive ion measurement and negative ion measurement of the first part of the measurement operation, and sets the polarity of the subsequent measurement operation based on the measurement result. It may be performed repeatedly in a predetermined period. Furthermore, a liquid chromatograph is provided as a means for supplying the separated and ionized sample introduced into the ionization means, wherein the mass analysis part is constituted by an ion trap type mass analysis part for performing ion trap type mass analysis. Alternatively, it is also possible to use means by capillary electrophoresis.

  As is clear from the above detailed description, according to the first invention described above, even when a separation means capable of separating a sample at a high speed is used, the measurement accuracy is not reduced, and the environment is not degraded. A mixture sample with various chemical properties including related substances and biological substances can be converted to unknown substances at high speed by adopting an ion trap mass analyzer and a series of measurement operations of positive ion measurement and negative ion measurement. An excellent effect is achieved that it is possible to provide a mass spectrometer that can be measured and can reduce the labor of the operator.

  Furthermore, according to the second invention, an appropriate substance is automatically selected and set for the sample by positive ion measurement, negative ion measurement, and determination performed at the beginning of measurement. In this measurement, it is possible to provide a mass spectrometer that can perform higher-speed measurement and reduce the labor of the operator without repeating positive ion measurement and negative ion measurement. Achieve excellent effect.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

  First, FIG. 4 shows a mass spectrometer according to an embodiment of the present invention using a mass spectrometer having an ion trap type mass analyzer. In the figure, a liquid chromatograph 1 includes a liquid feed pump 2, a mobile phase solvent tank 3, a sample injector 4, a separation column 5 and a pipe 6. The mobile phase solvent is sent to the separation column 5 at a constant flow rate by the liquid feed pump 2. On the other hand, the mixture sample is introduced from a sample injector 4 disposed between the liquid feed pump 2 and the separation column 5. Then, the sample that has reached the separation column 5 is separated by the interaction with the filler filled in the separation column 5. The sample separated by the liquid chromatograph 1 is introduced into the ion source 7 described below together with the mobile phase solvent.

  There are various types of ion sources. In this embodiment, an electrostatic spray method will be described as a typical example. The sample that has reached the ion source 7 by this electrostatic spraying method is introduced into the metal tube 9 via the connector 8. When a high voltage of several kilovolts is applied between the metal tube 9 and the electrode 10 disposed opposite to the metal tube 9, for example, by a high-voltage power supply 11, the end of the metal tube 9a is applied to the counter electrode 10. Electrostatic spraying occurs along the direction of. In addition, the solution flow rate which can maintain an electrostatic spray stably by this is about several microliters per minute. However, the flow rate of the solution sent from the liquid chromatograph 1 to the ion source 7 is about 1 milliliter per minute. Therefore, an atomizing gas 13 supplied from the gas supply pipe 12 is flowed from the outside of the metal pipe 9, and electrostatic spraying is assisted by this gas.

  Note that the droplets generated by the electrostatic spray include ions related to sample molecules. Therefore, gaseous ions are obtained by drying the droplets. The ions generated in this way are exhausted by the exhaust system 15b through the ion introduction pores 14a that open to the counter electrode 10, the differential exhaust part 16 exhausted by the exhaust system 15a, and the ion introduction pores 14b. The vacuum unit 17 is introduced. The ions introduced into the vacuum unit 17 are converged by an ion focusing lens composed of electrodes 18a, 18b, and 18c, and then introduced into a so-called ion trap type mass analyzing unit. The gate electrode 21 is provided to control the incidence of ions into the ion trap mass spectrometer.

  Next, the principle of operation of the ion trap mass spectrometer will be described. The so-called ion trap mass spectrometer is composed of end cap electrodes 19 a and 19 b and a ring electrode 20. FIG. 5 shows the amplitude of the high-frequency voltage applied to the ring electrode 20 and the gate electrode 21 when positive ions are measured during the acquisition of one mass spectrum in the ion trap mass spectrometer. This shows the temporal change (control waveform) of the voltage.

  That is, in the ion trap mass spectrometer, first, in the ion accumulation section 101, a high-frequency voltage is applied to the ring electrode 20, and a potential for ion confinement in a space surrounded by the ring electrode 20 and the end cap electrodes 19a and 19b. Form. For example, when analyzing positive ions, the voltage applied to the gate electrode 21 is lowered so that the ions can pass through the gate voltage 21 as shown in the figure. As a result, the ions taken into the vacuum unit 17 are then converged by the focusing lens, and enter the space surrounded by the ring electrode 20 and the end cap electrodes 19a and 19b from the opening of the end cap electrode 19a. A collision gas such as helium is introduced into the space surrounded by the ring electrode 20 and the end cap electrodes 19a and 19b, and the pressure is maintained at about 1 millitorr. That is, the ions lose energy by colliding with the collision gas molecules, and are confined in the confinement potential formed in the space surrounded by the ring electrode 20 and the end cap electrodes 19a and 19b.

  Next, in the scan section 102, the voltage applied to the gate electrode 21 is increased so that ions cannot pass through the gate electrode 21 (off state). By gradually increasing the amplitude of the high-frequency voltage applied to the ring electrode 20, the orbit is sequentially increased in the order of the value obtained by dividing the mass of the ion by the charge of the ion (hereinafter referred to as m / z). Becomes unstable, and is discharged from the openings provided in the end cap electrodes 19a and 19b to the outside of the mass spectrometer. The discharged ions are detected by the ion detector 22, and the detected signal is sent to the data processing device 24 via the signal line 23 and processed.

  Thereafter, after the end of the scan section 102, the voltage applied to the ring electrode 20 is turned off to eliminate the ion confinement potential, thereby removing ions remaining in the mass spectrometer (residual ion removal section 103). Then, in the ion trap mass spectrometer, by repeating such a series of operations (ion accumulation 101, scan 102, residual ion removal 103), the sample sequentially sent from the liquid chromatograph 1 is converted to the m / Mass spectrometry is performed in order from ions with the smallest z, and thus components of the mixture sample containing various substances can be identified at high speed.

  Further, FIG. 1 attached shows a configuration including the configuration of the control system in addition to the configuration of the mass spectrometer having the ion trap type mass analyzer shown in FIG. That is, the sample injector 4 is connected to an autosampler 25 for automatically introducing a sample. The sample set in the autosampler 25 is sent from the sample injector 4 to the separation column 5 and separated. Then, the separated sample is introduced into the ion source 7 together with the mobile phase solvent in the same manner as described above. The sample that has reached the ion source 7 is also introduced into the metal tube 9 through the connector 8, and a high voltage is applied to the metal tube 9 by the high-voltage power supply 11 to generate electrostatic spray. The same is true.

  The ions generated by the ionization by electrostatic spraying are opened in the first ion introduction pore 14a opened in the counter electrode 10, the differential exhaust part 16 exhausted by the exhaust system 15, and the apertured electrode 26. Then, it is introduced into the vacuum part 17 exhausted by the exhaust system 15b through the second ion introduction pore 14b. A voltage is applied to the counter electrode 10 by a drift voltage power source 27. In addition to the effect of improving the ion transmissivity of the ion introduction pore 14b by drifting ions taken into the differential exhaust portion 16 in the direction of the second ion introduction pore 14b, The gas molecules remaining in the differential exhaust section 16 and ions collide with each other, thereby desorbing solvent molecules such as water adhering to the ions.

  Further, an acceleration voltage is applied to the apertured electrode 26 by an acceleration voltage power supply 28. This acceleration voltage affects the energy (incident energy) when ions pass through the opening provided in the end cap electrode 19a. That is, since the ion confinement efficiency of the ion trap mass spectrometer depends on the incident energy of the ions, the acceleration voltage is set so as to increase the confinement efficiency.

  Further, the ions introduced into the vacuum unit 17 are converged by an ion focusing lens constituted by the electrodes 18a, 18b, and 18c, and then introduced into the ion trap type mass analysis unit through the ring-shaped gate electrode 21. The As described above, a collision gas such as helium is introduced from the gas supply unit 29 into the mass spectrometer through the gas introduction pipe 30. Insulation between the end gap electrodes 19 a and 19 b and the ring electrode 20 is performed by a quartz ring 31. The electrodes 18a, 18b and 18c are connected to an ion focusing lens power supply 38, and the gate electrode 21 is connected to a gate electrode power supply 39.

  The ions subjected to mass analysis as described above and discharged out of the mass analysis unit are then detected by a detector configured by the conversion electrode 33, the scintillator 34, the photomultiplier 35, and the like. That is, the discharged ions collide with the conversion electrode 33 to which a voltage for accelerating the ions is applied by the conversion electrode power source 32. Due to the collision between the ions and the conversion electrode 33, charged particles are emitted from the surface of the conversion electrode 33. The charged particles are detected by the scintillator 34, and the detection signal is amplified by the photomultiplier 35. The scintillator 34 and the photomultiplier 35 are connected to a scintillator power supply 36 and a photomultiplier power supply 37, respectively. The detected signal is sent to the data processing device 24. The liquid chromatograph 1 and the ion trap mass spectrometer are controlled by a controller 41 (not shown, but includes a control power supply, a control circuit, control software, and the like). That is, as shown in the figure, the control unit 41 includes the autosampler 25, the high voltage power supply 11, the drift power supply 27, the acceleration voltage power supply 28, the ion focusing lens power supply 38, the gate electrode power supply 39, the data processing device 24, and the conversion electrode power supply. 32 to control these.

  Next, an example of a control method in a mass spectrometer having an ion trap type mass analyzer whose configuration has been described in detail above is shown in FIG. In this measurement control method, a method of alternately performing positive ion measurement and negative ion measurement is employed. That is, as shown in the figure, by using the positive ion measurement mode and the negative ion measurement mode alternately, information on positive ions and information on negative ions are obtained in a single measurement, so that environment-related substances and biological related information can be obtained. Mixture samples having various chemical properties including substances can be measured at a high speed while reducing the labor of the operator.

  In this control method, as shown in FIG. 2, first, the ionization mode (401, 402) of the ion source and the ion transmission mode ( 301, 302) and the ion detection mode (501, 502) of the detector. As for the voltage applied to the gate electrode 21, a section (201) for transmitting ions and a section (202) for shielding ions are alternately provided, but the polarity of the applied voltage is reversed depending on the ionization mode. In this way, by using the positive ion analysis mode and the negative ion analysis mode alternately, information on positive ions and negative ions can be obtained by a single measurement operation. The device can be used without being bothered by the setting of the device.

  At that time, by adopting the above-mentioned ion trap type mass analysis unit, the period for acquiring the mass spectrum while switching the polarity will be described later. Compared to a mass spectrometer of the type, it is possible to shorten the time significantly (for example, about 0.2 seconds to acquire one mass spectrum), so a separated sample is supplied to the mass spectrometer. Even if the liquid chromatograph 1 is a so-called high-speed separation means in which the time width of a sample to be separated and supplied is, for example, about several seconds by capillary electrophoresis, analysis with high accuracy with sufficient measurement points becomes possible.

  In order to reverse the polarity of the ions to be measured, the polarity of the voltage applied to the ion source, an ion optical system such as an ion trajectory focusing lens, the ion detector 22 and the like must be reversed. For example, in the above electrostatic spray ion source, a high voltage is applied between the metal tube 9 and the counter electrode 10, but a positive potential is applied to the metal tube 9 in the positive ion measurement mode, and a metal tube in the negative ion measurement mode. A negative potential is applied to 9. Similarly, the polarity of the voltage applied to the ion optical system and the detector must be reversed in accordance with the polarity of the ion to be measured.

  Further, in the portion where these polarities are reversed, it is particularly important to switch the ionization mode of the ion source. When the electrostatic spray ion source is used as an example, a positive several kilovolts are applied to the metal tube 9 in the positive ion measurement mode, and a negative several kilovolts are applied in the negative ion measurement mode. Immediately after the polarity of the voltage applied to the metal tube 9 is reversed, ion generation becomes unstable. Although no detailed study has been made as to how long it takes for the ion generation to become stable after reversing the polarity, it is estimated from the experience of the present inventors so far that 0. It seems to be around 05 seconds. Therefore, when the ionization mode is switched in the residual ion removal section 103 after the series of operations for acquiring the mass spectrum (ion accumulation section 101, scan section 102) is completed, it is necessary to wait for a while until the next ion accumulation section 101. I must. In order to reduce this waiting time, the ion source mode may be switched in the scan section 102 as shown in FIG.

  Further, it is preferable that the switching of the ion optical system and the polarity inversion of the gate voltage are synchronized with the switching of the ionization mode of the ion source. However, as described above, the ionization mode of the ion source is not switched immediately. . Therefore, when the ionization mode of the ion source is converted, it is preferable to provide an ion generation stop section 403, and in this ion generation stop section 403, the ion optical system is switched and the polarity of the gate voltage is reversed.

  Further, the voltage of the ion detector 22 may be reversed in the ion accumulation section 101 or the residual ion removal section 103. This is because ions are detected in the scan section 102. In the present embodiment, as shown in FIG. 2, the positive ion detection section 501 and the negative ion detection section 502 in the ion detector 22 are alternately provided.

  In summary, the ion source mode switching, the gate voltage, and the polarity inversion of the ion optical system can be performed in the scan section 102 or the residual ion removal section 103. However, these switching may be synchronized. desirable. The mode switching of the ion detector 22 can be performed in the ion accumulation section or the residual ion removal section 103.

Here, for reference, an example of voltages applied to the respective portions in the positive ion measurement mode and the negative ion measurement mode will be described below.
(1) Positive ion measurement mode metal tube (9): 3 kV
Electrode with open first pore (10): 60V
Electrode (26) opening the second pore: 10V
First electrode (18a) of ion focusing lens (electrostatic lens): -120V
Second electrode (18b) of ion focusing lens (electrostatic lens): −30V
Third electrode (18c) of ion focusing lens (electrostatic lens): -120V
Gate electrode (21, at the time of ion transmission, that is, on state): −60V
Gate electrode (21, when ion is blocked, that is, in an off state): 60 V
Conversion electrode (33): -5 kV
Scintillator (34): 10 kV
Photomultiplier (35): 500V
(2) Negative ion measurement mode metal tube (9): -3 kV
Electrode (10) having an opening in the first pore: -60V
Electrode (26) opening the second pore: -10V
First electrode (18a) of ion focusing lens (electrostatic lens): 120V
Second electrode (18b) of ion focusing lens (electrostatic lens): 30V
Third electrode (18c) of ion focusing lens (electrostatic lens): 120V
Gate electrode (21, during ion transmission, that is, in an on state): 60V
Gate electrode (21, when ion is blocked, that is, in an off state): −60V
Conversion electrode (33): 2.5 kV
Scintillator (34): 10 kV
Photomultiplier (35): 500V
In the present embodiment, the same sign voltage is used for the scintillator 34 and the photomultiplier 35 regardless of the polarity of ions to be measured. This is because the scintillator mainly detects electrons emitted from the conversion electrode 33. It should be noted that it is basically desirable to apply a voltage whose polarity is reversed and equal in absolute value to the parts other than the scintillator 34 and the photomultiplier 35. However, the voltage applied to the conversion electrode 33 is positive / negative. It is preferable to use a voltage having a different absolute value in each measurement mode.

  This is because, in negative ion measurement, when a high voltage (for example, 5 kV) is applied to the conversion electrode 33, the potential difference between the conversion electrode 33 and the scintillator decreases, and electrons emitted from the conversion electrode 33 efficiently enter the scintillator 34. By not reaching. In such a state, when the voltage applied to the conversion electrode 33 is increased, a phenomenon that the effective detection sensitivity is lowered occurs. Therefore, in order to prevent such a phenomenon, as described in the above embodiment, the voltage of the absolute value different in the positive and negative measurement modes (the optimum voltage is affected by the shape and arrangement relationship of the electrodes, When determining the applied voltage, an optimum value may be obtained by experiment) or applied to the conversion electrode 33 so that the potential difference between the conversion electrode 33 and the scintillator 34 does not become small. The voltage of the scintillator 34 may be changed according to the voltage to be applied.

  By the way, in general, the measurement time by the ion trap mass analyzer is about 0.1 seconds in the ion accumulation section 101, about 0.1 seconds in the mass analysis section 102, and about 0.01 seconds in the residual ion removal section 103. is there. For this reason, the time required for acquiring one mass spectrum by the ion trap mass spectrometer is about 0.2 seconds. Therefore, even if the positive ion measurement and the negative ion measurement are alternately performed by the mass analysis unit including the ion trap mass analysis unit, a spectrum having both positive and negative polarities can be obtained in about 0.4 seconds. it can. This is sufficient compared to the time span during which the sample is sent from a separation means such as a high-speed liquid chromatograph (generally, approximately 1 minute for liquid chromatograph and approximately several seconds for capillary electrophoresis). Short. Therefore, even if both positive and negative polarities are measured, mass spectra can be collected at practically sufficient time intervals.

  Further, switching between positive ion measurement and negative ion measurement is not only performed every time one mass spectrum is acquired as described above, but may be switched after acquiring two or more spectra. For example, even if five spectra are acquired in the positive ion measurement mode and then switched, and five spectra are acquired in the negative ion measurement mode, the time required to perform one series of positive ion measurement and negative ion measurement Is about 2 seconds, and sufficiently accurate analysis is possible even when judged from the time width during which the sample is sent from the liquid chromatograph 1 described above.

In addition, depending on the sample, it is detected as a positive ion ((M + H) ⁺ , where M represents a sample molecule and H represents a proton) with protons added in the positive ion measurement mode, and proton desorption in the negative ion measurement mode. Some are detected as negative ions ((M−H) ⁻ ). Therefore, it is useful to compare the mass spectra of both polarities when determining the molecular weight of a sample. That is, when the mass spectrum obtained by the positive ion measurement is compared with the mass spectrum obtained by the negative ion measurement and the molecular weight of the ions is measured with a deviation of 2 atomic mass units, The intermediate molecular weight measured by ion measurement is the true molecular weight of the sample.

  In the above-described embodiment, a method using electrostatic spray ionization has been described as an example. However, the present invention is effective regardless of the ionization method. For example, so-called atmospheric pressure chemical ionization (corona discharge utilization type), atmospheric pressure spray ionization (heating spray utilization type), and sonic spray ionization (high-speed gas flow utilization type) can be used. This is because when these ionization methods are used, positive ions added with protons of biological materials and negative ions released from protons can be generated in the same way as electrostatic spray ionization. This is because negative ions may be measured.

  The above electrostatic spray ionization, atmospheric pressure chemical ionization, atmospheric pressure spray ionization, and sonic spray ionization are collectively referred to as atmospheric pressure ionization in the art. However, the pressure at the portion where the ion source is arranged is not necessarily atmospheric pressure. For example, in the case of electrostatic spray ionization, when a high voltage is applied to the metal tube 9, the pressure is such that a discharge phenomenon that prevents the electrostatic spray ionization phenomenon does not occur between the metal tube 9 and the counter electrode 10. Can be used in a range. That is, the ion source may be arranged at a position where the pressure is within a range that does not impair the ion generation mechanism in each ionization method.

  Next, a second embodiment of the present invention will be described with reference to FIG. In the first embodiment, the mass analysis unit alternately performs positive ion measurement and negative ion measurement, thereby obtaining a positive ion mass spectrum and a negative ion mass spectrum in one measurement operation. A mass spectrometer that implements this method has been described. However, in the present invention, it is not always necessary to alternately perform positive ion measurement and negative ion measurement.

  That is, when the characteristics of the sample are not known in the analysis of the unknown sample, positive ion measurement is performed in the second embodiment as in the first embodiment, only during a predetermined period at the start of analysis. By alternately performing negative ion measurement and negative ion measurement, it is determined which polarity is suitable for measurement. That is, by comparing the results obtained by carrying out the positive ion measurement and the negative ion measurement, it is determined which of the positive and negative ion measurements is suitable for the target sample. Subsequent measurements are set by selecting an appropriate polarity capable of analyzing the target sample.

  FIG. 3A shows the timing indicating the method for selecting the ion polarity in the second embodiment. First, after introducing the sample and starting the measurement, the negative ion measurement interval 601 and the negative ion measurement interval 601 are negative. An ion measurement section 602 is provided to acquire a mass spectrum of positive ions and a mass spectrum of negative ions. In the second embodiment, instead of using the separation means such as the liquid chromatograph and capillary electrophoresis described above, the sample solution is always introduced into the ion source with a syringe pump or the like. An example using flow injection analysis will be described. The positive ion measurement in the positive ion measurement section 601, the negative ion measurement in the negative ion measurement section 602, and the means for polarity conversion of the ions to be measured are the same as those in the embodiment shown in FIG. It can be realized by configuration.

  Then, following the positive / negative ion measurement section (601, 602), in the next determination section 603, the mass spectra obtained in both the measurement sections are compared. Thereby, it is determined in which measurement section the mass spectrum obtained clearly captures ions derived from the sample. Various determination methods can be considered as this determination method. For example, the above-described data processing device 24 and the control are controlled so that, for example, the intensity of ions derived from a sample is compared and the stronger one is selected. What is necessary is just to program the apparatus 41 grade | etc.,. In the present embodiment, this determination is automatically performed by the data processing device 24, and the determination result is sent to the control device 41. Thereafter, measurement is performed with the polarity selected in the determination section 603 (in the example of FIG. 3A, positive ions are present and the positive ion measurement section (601) continues).

  FIG. 3B shows a method procedure for carrying out the second embodiment of the present invention in an analyzer in which a separation means such as LC / MS and a mass spectrometer are combined. When the above separation means is used, (1) solvent, (2) sample that can be analyzed by positive ion measurement, (3) sample that can be analyzed by negative ion measurement, or (4) either positive or negative ion measurement. Samples that can be analyzed are sequentially sent to the ion source with a time difference.

  However, in the analysis of an unknown sample, it is impossible to predict what kind of sample will be sent at what timing. Therefore, as shown in FIG. 3B, a positive ion measurement section 601, a negative ion measurement section 602, and a discrimination section 603 are sequentially provided at the beginning of the operation sequence. In addition, when the signal obtained by this is the ion derived from a solvent, it waits for a sample to be sent, repeating these operation. Thereafter, when ions derived from the sample are detected, the polarity suitable for analyzing the sample is determined and selected, and measurement is performed.

  In general, from the separation means as described above, one sample is introduced into the ion source in a time width of several seconds to several minutes, and thereafter, a different substance is introduced into the ion source. Therefore, after the first positive ion measurement section 601, the negative ion measurement section 602, and the discrimination section 603, a certain period of time (this period depends on the separation means, but in the case of LC / MS, for example, 5 seconds. Degree), measurement is performed with one polarity discriminated by the discrimination section 603. After the measurement with this one polarity is performed, similarly to the above, the positive ion measurement section 601, the negative ion measurement section, and the discrimination section 603 are provided in order, and again whether the positive ion measurement is suitable or negative ion measurement. Make sure that is suitable. Thereafter, measurement is performed according to the polarity determined in the determination section 603, and this is repeated a predetermined number of times. As described above, in the second embodiment, an appropriate polarity is automatically selected and set by the positive ion measurement, the negative ion measurement, and the determination performed at the beginning of the measurement. Even in the measurement of substances, faster measurement is possible without repeating positive ion measurement and negative ion measurement.

  Note that the above-described determination and polarity switching control of each part necessary for the analyzer are performed by the control device 41, and when it is determined that the sample can be measured either positively or negatively, Polarity may be used, but as mentioned above, the true molecular weight of the sample can be estimated from the difference in molecular weight obtained by positive and negative measurements. The polarity may be measured alternately. Furthermore, in the above, in order to achieve a high-speed measurement operation, the mass analyzer that performs mass analysis on the separated and ionized mixture sample is preferably configured by the ion trap mass spectrometer. However, in the present invention, the present invention is not limited to this, and other general mass spectrometers may be used as the separation means within the range where a desired speed can be obtained depending on the introduction speed of the introduced mixture sample. It would be possible to adopt it.

  As described above, according to the above embodiment of the present invention, if the operator sets the sample in the autosampler (or syringe pump) and starts the analysis, then the control device 41 of the mass spectrometer is used thereafter. Thus, the apparatus itself automatically carries out the positive and negative measurement modes alternately, or automatically selects the measurement mode having the polarity suitable for the sample and acquires the analysis data. Therefore, the operator can perform high-speed measurement with high accuracy without selecting and considering the sample characteristics, especially positive and negative measurement modes, and complete the analysis in one operation. Therefore, the burden on the operator can be reduced.

It is a figure which shows the whole structure also including a control part of the mass spectrometer provided with the ion trap type | mold mass spectrometer which becomes embodiment of this invention. It is a figure which shows the timing which applies the voltage of each part in the mass spectrometer of the said invention, and the timing which converts a mode. It is a figure which shows the method of selecting the ion polarity in the 2nd Embodiment of this invention. It is a figure which shows the structure of the liquid chromatograph / mass spectrometer in the mass spectrometer of the said invention. It is a figure which shows the timing which applies a voltage to the ion trap type | mold mass spectrometry part in the said liquid chromatograph / mass spectrometer.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Liquid chromatograph, 2 ... Liquid feed pump, 3 ... Mobile phase solvent tank, 4 ... Sample injector, 5 ... Separation column, 6 ... Piping, 7 ... Ion source, 8 ... Connector, 9 ... Metal pipe, 10 ... Opposite Electrode, 11 ... Power supply, 12 ... Gas supply pipe, 13 ... Gas for spraying, 14a, 14b ... Ion introduction pore, 15a, 15b ... Exhaust system, 16 ... Differential exhaust part, 17 ... High vacuum part, 18a, 18b , 18c ... electrode, 19a, 19b ... end cap electrode, 20 ... ring electrode, 21 ... ring-shaped gate electrode, 22 ... detector, 23 ... signal line, 24 ... data processing device, 101 ... ion accumulation section, 102 ... scan Section: 103 ... Residual ion removal section, 201 ... Ion shielding section by gate electrode, 202 ... Ion permeation section by gate electrode, 301 ... Positive ion measurement section of mass spectrometer, 302 Negative ion measurement section of mass spectrometer, 401 ... Positive ion generation section in ion source, 402 ... Negative ion generation section in ion source, 403 ... Ion generation stop section, 501 ... Positive ion detection section in detector, 502 ... Detector Negative ion detection interval at.

Claims (7)

A separation unit for separating the mixed sample;
An ionization unit that ionizes the sample separated by the separation unit by electrostatic spraying;
Ion-introducing pores for taking in the ions related to the sample generated in the ionization section into vacuum,
An ion trap portion for trapping ions introduced from the ion introduction pore;
A detector for detecting ions from the ion trap unit;
A mass spectrometer comprising: a control unit that compares a result obtained by measuring positive ions and negative ions and selects a polarity having a higher ionic strength of the sample as a measurement polarity.   The mass spectrometer according to claim 1, wherein the control unit sets a measurement polarity in a subsequent measurement operation based on measurement results of positive ion measurement and negative ion measurement.   2. The mass spectrometer according to claim 1, wherein the controller repeatedly performs positive ion measurement, negative ion measurement, and measurement polarity setting in a measurement operation performed based on the measurement result. Mass spectrometer.   The mass spectrometer according to claim 1, wherein the separation unit is a liquid chromatograph or a capillary electrophoresis unit. An ionization unit for ionizing the sample;
An ion trap part for confining ions generated in the ionization part;
A mass spectrometer comprising a detector for detecting ions discharged from the ion trap unit,
The ion trap section has an ion accumulation section for confining ions;
The ionization section alternately generates positive ions and negative ions, and the ionization mode of the ionization section is switched outside the ion accumulation section of the ion trap section, and the detector The mass spectrometer is characterized in that polarity switching is performed in the ion accumulation section of the ion trap section .   2. The mass spectrometer according to claim 1, wherein the separation unit is separation means having a time width of separating and feeding the mixed sample in a liquid phase for 1 minute or less. The mass spectrometer according to claim 1 ,
The ion trap section has an ion accumulation section for confining ions;
The ionization section alternately generates positive ions and negative ions, and the ionization mode of the ionization section is switched outside the ion accumulation section of the ion trap section, and the detector The mass spectrometer is characterized in that polarity switching is performed in the ion accumulation section of the ion trap section.

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