JP4839276B2 - Liquid chromatograph mass spectrometer - Google Patents

Description

  The present invention relates to a liquid chromatograph mass spectrometer.

  Liquid chromatography at a flow rate of several hundred μL / min or more is a general means for separating a sample in which a plurality of components are mixed. A mass spectrometer, which is one of sample detection means of a liquid chromatograph, is an analyzer that ionizes sample molecules and introduces them into a vacuum, and controls the electric field in the vacuum to determine the mass of the sample molecules. The ion source of the mass spectrometer is an electrospray ion source (ESI) using an electrospray ionization method, an atmospheric pressure chemical ion source (APCI) using an atmospheric pressure chemical ionization method, and a sonic spray ion using a sonic spray ionization method. A source (SSI) is commonly used. In any ionization method, the sample solution eluted from the liquid chromatograph is sprayed to increase the vaporization efficiency of the generated sample droplets, thereby improving the ionization efficiency.

  When spraying a sample solution of several hundred μL / min eluted from the liquid chromatograph, it is difficult to vaporize all the sample droplets before they are introduced into the mass spectrometer because of the high flow rate.

  There is a method of introducing a dry gas, which helps vaporize the sprayed sample droplets, into the sample droplets in order to increase the vaporization efficiency of the sample droplets. In this case, in order to sufficiently vaporize the sample droplet, it is necessary to sufficiently stir the sample droplet and the dry gas. For example, as shown in Patent Document 1, the sample spraying portion and the dry gas introduction direction are In the case of the coaxial, the gas and sample droplets are not sufficiently stirred and the vaporization efficiency is low, and the concentration of the vaporized sample is diluted with the dry gas, so that the ionization efficiency is reduced in APCI, and other ion sources. However, there is a problem that the sensitivity is lowered as a result of a decrease in efficiency of introducing the sample into the MS portion.

  On the other hand, for example, as shown in Patent Document 2 and Patent Document 3, in the case where the drying gas is introduced from the axial direction intersecting the sample spraying portion, a large amount is required to sufficiently dry the sample droplet. As a result, the concentration of the vaporized sample is diluted with the gas and the ionization efficiency is lowered in APCI, and the efficiency of introducing the sample into the MS section is lowered in other ion sources, resulting in a decrease in sensitivity. There was a problem.

  In addition, when a sample droplet that is insufficiently vaporized directly hits the sample introduction part of the mass spectrometer, the temperature of the sample introduction part is lowered and the sensitivity of the mass spectrometer is lowered. In order to avoid this, the ion source that ionizes the sample at this flow rate is designed so that the sample droplets that are insufficiently vaporized do not directly hit the sample introduction part of the mass spectrometer and the spray part of the ion source. And a method of spraying a sample from a direction orthogonal to the sample introduction part. In this case, since the distance between the sample droplet sprayed from the spray section and the sample introduction section is farther than when sprayed from the front of the pore, the efficiency of sample introduction to the MS section is reduced, resulting in a problem of reduced sensitivity. It was.

JP 2003-83938 A US Pat. No. 5,412,208 US Pat. No. 6,759,650

  Of the plurality of ionization methods of the mass spectrometer, when a plurality of ionization methods are realized with the same ion source, convenience for the measurer is improved.

  In the case of an ion source that realizes both ESI and APCI, it is necessary that ESI and APCI share the sample spray mechanism and that ESI and APCI can be switched immediately according to the demands of the measurer. In any ionization method, it is necessary to maintain the same sensitivity determined by the ionization efficiency, the efficiency of sample introduction into the MS section, and the like.

  APCI sample spraying methods include a heating spraying method and a gas spraying method. For example, in the case of the heating spray system as shown in Japanese Patent Application Laid-Open No. 2000-314726, when switching from APCI to ESI, it is necessary to wait for a temperature drop of the heating block, and switching at high speed is impossible.

  Therefore, it is a problem to cope with APCI while maintaining the sensitivity of ESI based on ESI by the gas spray method. However, when APCI is performed by sample spraying by a gas spraying method, it is difficult to vaporize a sample solution compared to ESI because it is impossible to make sample droplets fine by Rayleigh splitting in ESI. In order to solve this problem, when a large amount of high-temperature dry gas is introduced into the sample droplet, vaporization is promoted, but the concentration of the vaporized sample is diluted with the dry gas, resulting in a decrease in ionization efficiency of APCI. Decreases. In addition, when vaporization of sample droplets with APCI is realized by an infrared lamp, it is possible to vaporize the sample while avoiding dilution of the sample, but dirt such as sample droplets tends to adhere to the lamp surface, As a result, there was a problem that the lamp was damaged.

  An object of the present invention is to provide a liquid chromatograph mass spectrometer having a highly sensitive ion source capable of high-speed switching between a plurality of ion sources (for example, between APCI / ESI).

  According to one aspect of the present invention, a separation means for separating a solution in which a plurality of sample components are mixed for each component, a solution eluted from the separation means is sprayed together with a gas, and a part of the sample is a first ion source. A sample spraying section that ionizes at a second position, a second ion source that ionizes a part of the sprayed sample components, a sample introduction section that introduces ions generated by the second ion source into a vacuum, and the sample introduction A liquid chromatograph mass spectrometer having a mass spectrometer for mass-separating ions introduced from the unit, the apparatus comprising a vaporizer that covers the sample droplet sprayed by the sample sprayer, and an exit area of the vaporizer Is smaller than the cross-sectional area of the vaporized portion.

  According to another aspect of the present invention, a separation unit that separates a solution in which a plurality of sample components are mixed for each component, and a sample that sprays a solution eluted from the separation unit together with a gas and electrospray ionizes a part of the sample. A spray part, a needle electrode that chemically ionizes a part of the sprayed sample component, a sample introduction part that introduces ions generated by the needle electrode into a vacuum, and ions introduced from the sample introduction part A liquid chromatograph mass spectrometer comprising a mass spectrometer that performs mass separation includes a vaporization unit that covers a sample droplet sprayed by the sample spray unit, and an outlet area of the vaporization unit is a disconnection of the vaporization unit. It is smaller than the area.

  According to the present invention, a sample spray mechanism is shared by a plurality of ion sources (for example, ESI and APCI), and in any ionization method, the sensitivity determined by the ionization efficiency, the efficiency of introducing the sample into the MS section, and the like is equally maintained. Therefore, it is possible to provide a liquid chromatograph mass spectrometer having a highly sensitive ion source capable of high-speed switching between a plurality of ion sources (for example, between APCI / ESI).

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 1 shows the configuration of an apparatus used in this embodiment. In this embodiment, a pipe 2 through which a sample solution eluted from the liquid chromatograph 1 is introduced into an ion source, a spray unit 3 for applying a high voltage to the sample solution to electrospray ionize the sample, and sprayed sample droplets A gas supply unit 4 and a gas pipe 5 for supplying a gas for drying the gas, a vaporization unit 6 for agitating the sample droplet and the heated gas, a partition plate 7 for promoting the agitation in the vaporization unit 6, and vaporization An outlet hole 8 on the partition plate 7 through which the sample and the solvent exit the vaporizing section 6, a needle electrode 9 for causing corona discharge for atmospheric pressure chemical ionization of the vaporized sample, and the spray section 3 during ESI or APCI The sample is ionized by the needle electrode 9 and the pores 11 for introducing the solvent into the mass spectrometer 10.

  First, when ESI is performed in the present embodiment, a high voltage of about 4 kV DC is applied to the spray unit 3, and no voltage is applied to the needle electrode 9. The sample component separated into a single component by the liquid chromatograph 1 is sent to the spray unit 3 through the pipe 2 together with the solvent. In the spray unit 3, the sample becomes charged droplets by electrospray ionization. Further, dry nitrogen gas is supplied from the gas supply unit 4 to the vaporization unit 6 through the gas pipe 5 at a flow rate of about 10 L / min. The sample droplet and the dry gas are agitated by the vaporizing unit 6 while colliding with the partition plate 7, and the sample droplet is vaporized. When the diameter of the sample droplet reaches a certain value or less due to vaporization, the droplet is instantly refined (Rayleigh splitting) due to repulsion between charges in the droplet, and the sample and solvent in the droplet are ionized. The ionized sample and solvent are discharged from the outlet hole 8 and introduced into the mass spectrometer 10 through the pores 11 for mass separation.

  Next, when APCI is performed in the present embodiment, no voltage is applied to the spray unit 3, and a high voltage of about 9 kV DC is applied to the needle electrode 9. The sample component separated into a single component by the liquid chromatograph 1 is sent to the spray unit 3 through the pipe 2 together with the solvent. The material is sprayed by the spraying unit 3 to become sample droplets. Further, dry nitrogen gas is supplied from the gas supply unit 4 to the vaporization unit 6 through the gas pipe 5 at a flow rate of about 10 L / min. The sample droplet and the dry gas are agitated by the vaporizing unit 6 while colliding with the partition plate 7, and the sample droplet is vaporized. The vaporized sample and solvent molecules are discharged from the outlet hole 8. At the tip of the needle electrode 9, corona discharge is generated by the applied high voltage, and molecules such as water existing in the vicinity of the needle electrode 9 are ionized to generate the atmospheric pressure chemical ionization unit 12. When the sample and the solvent gas discharged from the outlet hole 8 collide with ions in the atmospheric pressure chemical ionization unit 12, they take charge and become ions. The generated sample and solvent ions are introduced into the mass spectrometer 10 through the pores 11 and mass-separated.

  As described above, switching between ESI and APCI only changes the application part of the DC high voltage, and thus switching at high speed is possible.

  In the present embodiment, the diameter of the outlet hole 8 at the outlet of the vaporizer is smaller than the inner diameter of the vaporizer 6. Thereby, in ESI, the sample and solvent vaporized by the vaporization part 6 are discharged | emitted by high concentration in the pore 11 vicinity, Therefore The introduction efficiency to the mass spectrometer 10 improves. Moreover, since it discharges | emits to the atmospheric pressure chemical ionization part 12 in APCI, ionization efficiency goes up.

  In this embodiment, the center axis of the outlet hole 8 is closer to the pore 11 than the center axis of the spray section 3. Thereby, in the case of ESI, the ions generated in the vaporization unit 6 are collected in a portion closer to the pores 11, and the introduction efficiency into the mass spectrometer 10 is further improved. In the case of APCI, the droplets of the sprayed sample droplets that have a large diameter and are sprayed directly below the spraying unit 3 first hit the partition plate 7 below the vaporizing unit 6, and therefore do not hit the needle electrode 9. Since the stability of the atmospheric pressure chemical ionization unit 12 is improved, the ionization efficiency is stabilized. In addition, as shown in the example of FIG. 2, since the sample and the solvent vaporized in the vaporization unit 6 are discharged to a portion where the ion density of the atmospheric pressure chemical ionization unit 12 is high, the probability of collision with ions increases, and the ionization efficiency increases. Go up. Further, since the sample and the solvent vaporized in the vaporization unit 6 are discharged from the portion close to the pores 11, the efficiency of introducing the ionized sample into the pores 11 is increased.

  In addition, the central axis of the needle electrode 9 of the present embodiment is not on the same plane as the central axis of the pore 11 but is present at a position 2 mm away in a direction parallel to the central axis of the pore. Thereby, in the case of APCI, the atmospheric pressure generated between the needle electrode 9 and the pore 11 is that the sample and solvent gas discharged from the outlet hole 8 in front of the pore 11 is flowed between the needle electrode 9 and the pore 11 as shown in FIG. Since the influence on the chemical ionization unit 12 is reduced and the stability of the atmospheric pressure chemical ionization unit 12 is improved, the ionization efficiency is stabilized.

  In addition, since the partition plate in which the outlet hole 8 of the vaporization unit 6 of the present embodiment is arranged is made of metal, charging up due to charged droplets generated by ESI or ions of the sample and solvent does not occur.

  An inert gas such as nitrogen gas is used as the drying gas in this embodiment. Moreover, in order to accelerate | stimulate vaporization of a sample droplet, a dry gas can also be heated to about 500 degreeC. In addition, vaporization of the sample droplet can be promoted by providing a heater in the vaporizing section 6 or the partition plate 7 and heating from the outside.

  FIG. 4 shows a second embodiment of the present invention. The same code | symbol location as Example 1 is the equivalent which has the same thing or the same function. The present embodiment is an example in which the lamp 13 for realizing the atmospheric pressure photoionization is provided in the vicinity of the vaporization section 6 of the first embodiment, and the atmospheric pressure photoion source (APPI) mode is made possible. In the present embodiment, atmospheric pressure photoionization occurs in the vaporization unit 6 by using the material of the vaporization unit 6 as a material that transmits light emitted from the lamp 13.

  The combination of the first and second ion sources can be a combination that can realize a plurality of ionization methods among a plurality of ionization methods of the mass spectrometer. Furthermore, it is good also as a combination which can implement | achieve 3 or more ionization methods as needed. A plurality of ionization methods (for example, ESI and APCI) can be realized with a single unit for the mass spectrometer portion. In addition, the sample spray mechanism can be shared by a plurality of ionization methods. In addition, it is possible to immediately switch between a plurality of ionization methods according to the needs of the measurer and the necessity for measurement. In any ionization method, the sensitivity determined by the ionization efficiency, the efficiency of introducing the sample into the MS section, and the like can be maintained equally.

It is a block diagram of the 1st Example of this invention. It is the schematic of the atmospheric pressure ionization part in the 1st Example of this invention. It is the schematic which looked at the 1st example of the present invention from the upper direction. It is a block diagram of the 2nd Example of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Liquid chromatograph 2 Piping 3 Spraying part 4 Gas supply part 5 Gas piping 6 Evaporation part 7 Partition plate 8 Outlet hole 9 Needle electrode 10 Mass spectrometer 11 Pore 12 Atmospheric pressure chemical ionization part 13 Lamp

Claims (9)

Separation means for separating a solution in which a plurality of sample components are mixed for each component, an electrospray ion source for spraying a solution eluted from the separation means together with a gas to ionize the sample, and a sample using a needle electrode A liquid chromatograph mass spectrometer having an atmospheric pressure chemical ion source and a mass analyzer for mass-separating ions in a vacuum,
The electrospray ion source and the atmospheric pressure chemical ion source can be switched,
The atmospheric pressure chemical ion source is provided at a subsequent stage of the electrospray ion source,
The mass spectrometer includes pores for introducing ions into the interior,
The sample spray destination of the electrospray ion source has a partition plate that promotes stirring by collision, and the partition plate is provided with holes,
The partition plate has a disc shape,
The sample in the electrospray ion source is sprayed on the center of the partition disk,
The liquid chromatograph mass spectrometer according to claim 1, wherein the hole is provided at a position shifted from a center of the disk. In claim 1,
A liquid chromatograph mass spectrometer characterized by introducing a dry gas into the electrospray ion source. In claim 2,
A liquid chromatograph mass spectrometer, wherein the dry gas is heated. In claim 1,
A liquid chromatograph mass spectrometer characterized in that the vaporizing section is heated to 100 ° C. or higher. In claim 1,
The liquid chromatograph mass spectrometer characterized in that the partition plate is arranged perpendicular to the direction of travel of the sample. In claim 1,
The liquid chromatograph mass spectrometer characterized in that the hole is provided at a position where the distance from the hole to the pore is closer than the distance from the center of the disc to the pore. . In claim 1,
The needle electrode is arranged at a position where the tip thereof is shifted from the axis of the sample in the pore in the sample traveling direction. In claim 1,
A liquid chromatograph mass spectrometer characterized in that the partition plate is made of metal. In claim 1,
Furthermore, the liquid chromatograph mass spectrometer provided with the lamp | ramp which implement | achieves atmospheric pressure photoionization.

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