JPH06102246A - Mass spectrometer - Google Patents

Abstract

PURPOSE:To obtain a liquid chromatograph/mass spectrometer with an electrostatic spray ion source which enables the obtaining of the intensity of ions stably and intensely. CONSTITUTION:A spray tubule 11 is arranged with the axis thereof shifted from the center axis of a ion pickup pore. A sample solution eluted from a liquid chromatograph is introduced into the spray tubule 11 through a piping 2 and a connector 10. A voltage of several kV is applied between the spray tubule 11 and an opposed electrode 12 having an ion introduction pore 15 opened thereon to spray the solution electrostatically. A gas such as dry nitrogen flows at a gas jet port 13 for spraying. Liquid drops charged electrically are vaporized to generate ions, which are taken into a mass spectrometric section 6 through the ion introduction pore 15a, a differential exhaust part 19 and an ion introduction pore 15b. A barrier 20a is provided between the tip of the spray tubule 11 and the opposed electrode 12. This enables reduction in temperature changes in the perimeter of the ion introduction pores 15a and 15b thereby observing the intensity of ions stably.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus in which a liquid chromatograph and a mass spectrometer, which are particularly important for separating and analyzing poorly volatile substances such as proteins, are combined, that is, an interface in a liquid chromatograph / mass spectrometer.

[0002]

2. Description of the Related Art At present, the development of a liquid chromatograph / mass spectrometer is regarded as important in the field of analysis. The liquid chromatograph is excellent in separating the mixture but cannot identify the substance. On the other hand, the mass spectrometer has high sensitivity and excellent ability to identify the substance, but it is difficult to analyze the mixture. Therefore, a liquid chromatograph / mass spectrometer that uses a mass spectrometer as a detector of a liquid chromatograph is very effective for analyzing a mixture. For reference, a block diagram showing the entire configuration of a conventional liquid chromatograph / mass spectrometer is shown in FIG.
The sample solution eluted from the liquid chromatograph is pipe 2
Is introduced into the ion source. The ion source is controlled by the ion source power source 4 via a signal line 5a. The ions relating to the sample molecules generated by the ion source are introduced into the mass spectrometric section and subjected to mass spectrometric analysis. This mass spectrometer is evacuated to a vacuum by an exhaust system. The mass-analyzed ions are detected by the ion detector 8, and the detection signal is sent to the data processing device via the signal line 5b. Now, although the principle of a liquid chromatograph / mass spectrometer is simple,
Whereas liquid chromatographs handle samples in solution,
The incompatibility of mass spectrometers in dealing with ions in high vacuum makes the development of this method very difficult. Several methods have been developed to solve this problem. Among them, the most promising is the spray ionization method in which the eluate from the liquid chromatograph is sprayed and the sample molecules contained in the generated droplets are ionized and taken into the mass spectrometric section.

As an example of the spray ionization method, the electrostatic spray method described in Analytical Chemistry, 1987, 59, 2642 (Analytical Chemistry 59 (1987) 2642) will be described. FIG. 10 is a sectional view showing the structure of a liquid chromatograph / mass spectrometer equipped with an electrostatic spray ion source. The sample solution eluted from the liquid chromatograph 1 is introduced into the spray thin tube 11 via the pipe 2 and the connector 10. The spray thin tube 11 and the counter electrode 1
When a voltage of several kV is applied between the tip and the nozzle 2, the sample solution is in a cone state at the tip of the nebulization tube 11, and a so-called electrostatic atomization phenomenon occurs in which minute droplets are generated from the tip. In the electrostatic spraying method, a spraying gas jet port 13 is provided, and a spraying thin tube 11 is provided.
A gas such as nitrogen is flowed from around to facilitate atomization. Further, a gas such as nitrogen toward the generated fine droplets is provided on the counter electrode 12 side, and the vaporizing gas ejection port 14 is provided.
To accelerate vaporization of fine droplets. The ions generated through the above process are ion-introducing pores 15
Is directly introduced into a vacuum and is subjected to mass analysis by the mass spectrometric section 6 under high vacuum.

[0004]

The conventional method has the following problems. The flow rate of the sample solution that can be introduced into the electrostatic spray ion source is limited to about 10 microliters per minute, and if a sample solution exceeding this is introduced into the ion source, the ions cannot be stably observed. . This is because as the flow rate of the sample solution increases, the diameter of the droplets generated by electrostatic spraying increases, and it becomes difficult to vaporize the droplets and efficiently extract the ions contained in the droplets. . Further, when a droplet having a large diameter comes into contact with the vicinity of the ion-incorporating pores, the pore temperature is lowered, and a liquid film is formed to close the pores.

On the other hand, the flow rate of a commonly used liquid chromatograph is 200 to 1000 microliters per minute. Due to this incompatibility between the electrostatic spray ion source and the liquid chromatograph, conventionally, the eluate from the liquid chromatograph is divided by using a splitter, and only a small portion is introduced into the electrostatic spray ion source. The method was taken. However, it is difficult to operate a splitter with a separation ratio of 1: 100 stably,
The observed ionic strength was also not stable. Therefore, it has been desired to develop an electrostatic spray ion source capable of stably observing ions even when a sample solution is introduced at a high flow rate of several hundred microliters per minute.

FIG. 11 shows that the electrostatic atomization ion source is 200 minutes per minute.
Solution in microliters (water / methanol / 5% acetic acid)
And the average diameter of the droplets in the jet stream 17 obtained by applying a voltage of 4 kilovolts between the spray capillary 11 and the metal mesh 16 placed 15 mm away from the tip of the spray capillary. The result of having investigated the distribution of the number of particles is shown. The measurement was performed at a position 10 mm away from the tip of the spray capillary 11. Here, the number of particles is 0.
It represents the number of particles that have passed through a space of 03 cubic millimeters. The central portion of the jet stream contains large-diameter droplets generated by the pressure of the atomizing gas. The large droplets lower the temperature in the vicinity of the ion-introducing pores, which causes the ionic strength to decrease. On the other hand, as the distance from the center of the jet to the outer periphery decreased, the average particle size of the droplets decreased, and when the distance from the center of the jet was 3 mm or more, the particle size became constant. Therefore, by taking in only the droplets having a small particle size existing on the outer peripheral portion of the jet flow from the ion introduction pores, it is possible to reduce the decrease in the ion intensity due to the cooling of the ion introduction pores and to stably observe the ions. . An object of the present invention is to provide an electrostatic spray ion source capable of capturing ionic strength strongly and stably, and thereby to realize high sensitivity of a liquid chromatograph / mass spectrometer.

[0007]

[Means for Solving the Problems] In order to obtain the above-mentioned object, that is, to obtain an electrostatic spray ion source capable of obtaining a strong and stable ionic strength, a sample solution sent from a liquid chromatograph is introduced into one end of a spray capillary. An electrostatic spray ion source for electrostatically spraying ions from the other end of the spray capillary to generate ions,
In the mass spectrometer equipped with the ion introduction pores for introducing the generated ions into the vacuum portion, and the mass analysis portion for performing mass analysis of the introduced ions, the tip of the spray capillary and the ion introduction pores A barrier that prevents the center of the jet from coming into contact with the periphery of the ion introduction pore is provided between the opening and the electrode. More specifically, the cross-sectional shape of the barrier has a curvature on the outer circumference, such as a circular shape, an elliptical shape, or a streamline shape, in order to converge only the outer peripheral portion of the jet flow around the pores. In order to prevent the solution from accumulating in the barrier part, a heating mechanism for vaporizing the solution should be provided independently of the other parts of the ion source, or the barrier should be in the form of a thread whose axis direction vector has a component in the direction of gravity. Alternatively, it is composed of a rod-shaped object to help the solution flow down. Further, in order to assist the focusing of ions by the electric field, a mechanism for applying a potential to the barrier independently of the other parts of the ion source is provided.

[0008]

[Function] Since a barrier is provided between the narrow tube for spraying the sample solution and the pore for taking in ions, the vicinity of the center of the jet flow containing droplets with large particle diameter is prevented from coming into contact with the periphery of the pore.
It is possible to reduce the temperature drop in the pores, and thus to stably observe the ionic strength in the mass spectrometer. Further, by forming the outer wall surface of the barrier with a shape of curvature and converging the portion of the outer peripheral portion of the jet stream where a large number of small-sized droplets are obtained to the ion introduction pores by the air flow, it is possible to obtain a strong ionic strength. it can. Therefore, the ion intensity can be stably observed, and a highly sensitive mass spectrometer can be realized.

[0009]

Embodiments of the present invention will be described with reference to FIGS. FIG. 1 shows an electrostatic spray ion source which is a first embodiment according to the present invention, and shows a cross section of the electrostatic spray ion source in which a barrier is provided between the tip of the spray capillary and the counter electrode having the opening of the ion introduction pore. It is a figure. The axis of the spray thin tube 11 and the central axis of the ion-incorporating pore are displaced from each other. The sample solution eluted from the liquid chromatograph is the pipe 2 and the connector 10.
It is introduced into the spray thin tube 11 via. Between the spray thin tube 11 and the counter electrode 12 having the ion introduction pore 15a opened,
The solution is electrostatically sprayed by applying a voltage of several kilovolts using the power supply 18a. In order to assist the spraying, a gas such as dry nitrogen is made to flow from the spraying gas jet port 13. The charged droplets thus obtained are vaporized and ions are generated. The generated ions are introduced into the ion introduction pores 15
It is taken into the mass spectrometric section 6 through a, the differential evacuation section 19, and the ion introduction pore 15b. At this time, the barrier 20a is provided between the tip of the spray thin tube 11 and the counter electrode 12 to prevent the vicinity of the center of the jet flow from touching the electrode, and avoid the temperature change around the ion introduction pore 15a. Barrier 20a
Although a conductor is desirable, an insulating material may be used as the material of the barrier 20a when the barrier of the conductor may disturb the electric field near the tip of the spray capillary. When the surface of the barrier 20a is wetted by the solution and the spray becomes unstable, a heater 21 is attached to the barrier 20a in order to vaporize the solution by heat.
It may be heated independently of the other parts of the ion source. Further, the potential of the barrier 20 may be the same as the potential of the counter electrode 12, but in order to cause the charged droplets or ions to drift in the direction of the pores 15a, the power source 18b is used for the barrier 20a so that the barrier 20a is different from the rest of the ion source. The potential may be applied independently.
Further, even in the case of the configuration in which the central axis of the spray thin tube 11 is inclined with respect to the central axis of the ion introduction pore 15a, the barrier 2
The configuration in which 0a is provided is effective.

FIG. 2 is a view showing a second embodiment of the present invention, in which the axis of the atomizing capillary and the central axis of the ion introducing pore are inclined, and the tip of the atomizing capillary and the ion introducing pore are arranged. FIG. 3 shows a cross-sectional view of an electrostatic spray ion source in which a barrier is provided between the counter electrode and the counter electrode that opens. When the nebulized thin tube is inclined with respect to the center axis of the ion introduction hole, the vicinity of the center of the jet flow is 1
Since it is possible to take in only the outer peripheral portion of the jet flow from the ion introduction pores 15a at a position away from 5a, the ionic strength is reduced due to the temperature change of the ion introduction pores 15a and the liquid spread on the surface of the counter electrode 12 The problem that the membrane closes the ion introduction pores 15a is alleviated. However, with this configuration, it took about 10 minutes until the temperature equilibrium was reached around the ion introduction pores after the start of spraying. For this reason, there is a problem in performing quick measurement. Therefore, as shown in FIG. 2, the barrier 20a
Thus, by preventing the central portion of the jet flow from touching the counter electrode 12, the temperature of the counter electrode 12 can be kept constant at all times, and quick measurement becomes possible. The second aspect of the present invention
In the embodiment of FIG. 3, in the case of the configuration in which the central axis of the spray capillary is inclined with respect to the central axis of the ion introduction pore,
As shown in the cross-sectional view of the electrostatic spray ion source showing an example in which the barrier is changed in direction, the barrier 20a may be changed in direction.

FIG. 4 is a diagram showing a third embodiment of the present invention, in which an electrostatic spray ion source in which the outer wall surface of the barrier wall has a curvature so that only the outer peripheral portion of the jet converges to the ion introduction pores. FIG. The shape of the barrier may be plate-like or block-like as shown in FIGS. 1 to 3, but as shown in FIG. 4, the outer wall surface of the barrier 20b is made to have a curvature such as a circle, an ellipse, or a streamline, and sprayed. By controlling the flow of the working gas, the large-diameter droplets at the center of the jet flow are made to hit the barrier 20b and disappear, and only the portion of the outer periphery of the jet where many small-diameter droplets are obtained is ion-introduced. It can be converged to the pores 15a, and high sensitivity can be achieved.

FIG. 5 is a view showing a fourth embodiment of the present invention, and is a sectional view of an electrostatic spray ion source in which a barrier is constituted by threads, rods or an assembly thereof. As shown in FIG. 5, the barrier 20c may be formed by threads or rods arranged such that the axial direction vector has a component in the direction of gravity, or an assembly thereof. With such a configuration, the solution accumulated in the barrier 20c flows off along the thread or the rod, and thus the instability of the spray can be avoided. Further, in the configuration shown in FIG. 5, a mechanism for collecting the sample solution may be provided at the end of the thread or rod. FIG. 6 is a block diagram showing the configuration provided with a mechanism for collecting the solution.
Shown in. The solution sprayed from the ion source has a partial barrier 2
When it hits 0c, it travels along the thread or rod and flows away in the direction of gravity. A collection container 22 such as a fraction collector or a beaker is provided at the end of the thread or rod to collect the solution.
The solution recovered by the recovery container 22 is used as the photodetector 2
3 may be used for further analysis. Further, as described in FIG. 6, the solution flowing along the thread or the rod may be directly introduced into the photodetector 23. A mechanism for detecting the sample molecule and a mechanism for driving the barrier may be provided, the barrier may be removed only when the sample molecule is contained in the eluate from the liquid chromatograph, and the ions may be introduced into the mass spectrometer. . With this configuration, the measurement is performed only when the sample molecule can be analyzed, so that the temperature change of the pores and the contamination around the pores are reduced, and the amount of data stored in the data processing device is small. I'm done.

FIG. 7 is a block diagram showing a fifth embodiment of the present invention, in which the eluate from a liquid chromatograph is analyzed by a photodetector and a barrier is driven when a signal is obtained. is there. The eluate from the liquid chromatograph is introduced into the photodetector. In the case of a configuration in which a splitter is provided and only a part of the solution is introduced into the ion source, the solution may be introduced into the photodetector after being split by the splitter as shown in FIG. The signal from the photodetector is sent to the barrier 20d, the mass spectrometric section, and the data processing device by the signal line 5c. The barrier 20d is driven by the signal from the photodetector, and the mass spectrometric unit and the data processing device are operated to detect ions. FIG. 8 is a structural diagram showing an example of the barrier portion having the configuration shown in FIG. Movable barrier 20d
And a barrier support 24 that supports the movable part. When only the solvent is introduced into the spray capillary 11,
As shown in FIG. 8, the ion introduction pore 15a is covered with the barrier 20d. When the signal from the photodetector is sent, the barrier is removed and the ions are taken in through the ion introduction pores 15a, and at the same time, the mass spectrometric unit, the ion detector,
The data processor is activated and the analysis is performed. The configuration in which the mechanism for detecting the sample molecules and the mechanism for driving the barrier are provided is not limited to the electrostatic atomization method, and other spray ionization methods,
For example, it is also effective for the atmospheric pressure chemical ionization method and the atmospheric pressure spray ionization method.

[0014]

EFFECTS OF THE INVENTION According to the present invention, it is possible to prevent the liquid droplets generated by electrostatic spraying having a large particle diameter from coming into contact with the electrodes having the ion introduction pores. Furthermore, by giving the wall shape of the barrier wall a curvature, only small droplets can be taken into the vacuum portion from the ion-taking pores. Therefore, the temperature of the ion-incorporating pores does not change, and the ions can be stably and strongly observed in the mass spectrometric section.

[Brief description of drawings]

FIG. 1 is a sectional view of an electrostatic spray ion source according to a first embodiment of the present invention.

FIG. 2 is a sectional view of an electrostatic spray ion source according to a second embodiment of the present invention.

FIG. 3 is a cross-sectional view of an electrostatic spray ion source showing an example in which the direction of the barrier is changed and arranged in the second embodiment of the present invention.

FIG. 4 is a sectional view of an electrostatic spray ion source according to a third embodiment of the present invention.

FIG. 5 is a sectional view of an electrostatic spray ion source according to a fourth embodiment of the present invention.

FIG. 6 is a block diagram showing a configuration of an electrostatic spray ion source provided with a mechanism for collecting a solution.

FIG. 7 is a block diagram showing a configuration for performing mass spectrometry by providing a mechanism for detecting sample molecules and a mechanism for driving a barrier according to a fifth embodiment of the present invention.

FIG. 8 is a sectional view showing an example of an ion source portion of a fifth embodiment of the present invention.

FIG. 9 is a block diagram showing the configuration of a conventional liquid chromatograph / mass spectrometer.

FIG. 10 is a sectional view showing the structure of a liquid chromatograph / mass spectrometer equipped with a conventional electrostatic atomization ion source.

FIG. 11 is a diagram showing the relationship between the distance from the center of the jet and the average particle diameter and the number of particles of droplets contained in the jet generated by electrostatic spraying.

[Explanation of symbols]

1 ... Liquid chromatograph, 2 ... Piping, 3 ... Ion source, 4
... Ion source power supply, 5a, 5b, 5c ... Signal line, 6
... mass spectrometric section, 7 ... exhaust system, 8 ... ion detector, 9 ... data processing apparatus, 10 ... connector, 11 ... spray tube, 12
... counter electrode, 13 ... atomizing gas jet, 14 ... vaporizing gas jet, 15, 15a, 15b ... ion introduction pores, 1
6 ... Metal mesh, 17 ... Jet flow, 18a, 18b ... Power supply, 19 ... Differential exhaust part, 20a, 20b, 20c, 20
d ... Barrier, 21 ... Heater, 22 ... Recovery container, 23 ... Photodetector, 24 ... Barrier support part, 25 ... Splitter.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Atsushi Maki 1-280, Higashi Koikeku, Kokubunji, Tokyo Metropolitan Institute of Hitachi, Ltd. (72) Hideki Kambara 1-280, Higashi Koikeku, Kokubunji, Tokyo Hitachi, Ltd. Central Research Center

Claims (8)

[Claims] 1. An electrostatic spray ion source for generating ions by introducing a sample solution sent from a liquid chromatograph into one end of a spray capillary and electrostatically spraying from the other end of the spray capillary, and the generated ions. In a mass spectrometer equipped with an ion-introducing pore for introducing into the vacuum part, and a mass spectrometer for mass-analyzing the introduced ion, the tip of the spray capillary and the opening of the ion-introducing pore are opened. A mass spectrometer characterized in that a barrier is provided between the electrode and the electrode to prevent the central part of the jet generated by electrostatic spraying from coming into contact with the electrode where the ion introduction pore is opened. 2. The cross-sectional shape of the barrier has a curvature on the outer periphery such as a circle, an ellipse, or a streamline in order to converge the outer periphery of the jet flow to the periphery of the ion intake pores. The mass spectrometer according to claim 1, wherein: 3. The barrier is composed of at least one thread-shaped or rod-shaped object.
Alternatively, the mass spectrometer according to claim 2. 4. The mass spectrometer according to claim 3, wherein the vector of the central axis of the thread-shaped or rod-shaped object forming the barrier has a gravity direction component. 5. The mechanism according to claim 3 or 4, wherein a mechanism for collecting the sample solution flowing down through the thread-shaped or rod-shaped object is provided at the end of the thread-shaped or rod-shaped object. Any mass spectrometer. 6. The mass spectrometer according to claim 1, further comprising a mechanism for heating the barrier independently of other portions of the electrostatic spray ion source. . 7. The mass spectrometer according to claim 1, further comprising a mechanism for applying a potential to the barrier independently of other portions of the ion source. . 8. The mass according to claim 1, wherein a mechanism for detecting a sample molecule and a mechanism for driving the barrier are provided, and the barrier is driven in accordance with a detection signal. Analyzer.