JP3238488B2 - Mass spectrometer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

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

[0002]

2. Description of the Related Art At present, in the field of analysis, development of liquid chromatograph / mass spectrometer is regarded as important. Liquid chromatographs are excellent at separating mixtures but cannot identify substances, whereas mass spectrometers are sensitive and have excellent ability to identify substances, but the analysis of mixtures is difficult. Therefore, a liquid chromatograph / mass spectrometer using a mass spectrometer as a detector of the liquid chromatograph is very effective for analyzing a mixture. For reference, FIG. 9 is a block diagram showing the entire configuration of a conventional liquid chromatograph / mass spectrometer.
The sample solution eluted from the liquid chromatograph is
To the ion source. The ion source is controlled by a power source 4 for the ion source via a signal line 5a. Ions related to the sample molecules generated by the ion source are introduced into the mass spectrometer and subjected to mass analysis. The 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. By the way, the principle of a liquid chromatograph / mass spectrometer is simple,
While liquid chromatography deals with samples in solution,
The incompatibility of mass spectrometers handling ions in high vacuum has made the development of this method very difficult. Several methods have been developed to solve this problem. Among them, a promising one is a spray ionization method in which an eluate from a liquid chromatograph is sprayed, and sample molecules contained in the generated droplets are ionized and taken into a mass spectrometer.

As an example of the spray ionization method, an electrostatic spray method described in Analytical Chemistry 59 (1987) 2642, Vol. 59, p. 2642, 1987 will be described. FIG. 10 is a sectional view showing the structure of a liquid chromatograph / mass spectrometer provided with an electrostatic spray ion source. The sample solution eluted from the liquid chromatograph 1 is introduced into the spray capillary 11 via the pipe 2 and the connector 10. The spray capillary 11 and the counter electrode 1
When a voltage of several kV is applied between the sample solution 2 and the sample solution, a so-called electrostatic spraying phenomenon occurs in which the sample solution is in a cone state at the tip of the spray capillary 11 and microdroplets are generated from the tip. In the electrostatic spraying method, a spray gas outlet 13 is provided, and
A gas such as nitrogen is flowed from around to facilitate spraying. Further, a gas such as nitrogen is directed toward the generated microdroplets by a vaporizing gas outlet 14 provided on the counter electrode 12 side.
Spraying from the air to promote the vaporization of the microdroplets. The ions generated through the process described above are supplied to the ion introduction pore 15
Is directly introduced into a vacuum and mass analyzed by the mass spectrometer 6 under a 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. When a sample solution exceeding this flow rate is introduced into the ion source, ions cannot be observed stably. . This is because as the flow rate of the sample solution increases, the diameter of the droplet generated by electrostatic spraying increases, and it becomes difficult to vaporize the droplet and efficiently extract ions contained in the droplet. . Further, when a droplet having a large diameter comes into contact with the vicinity of the ion capturing pore, the temperature of the pore decreases, and a liquid film is formed to close the pore.

On the other hand, the flow rate of a commonly used liquid chromatograph is 200 to 1000 microliters per minute. Due to the incompatibility between the electrostatic spray ion source and the liquid chromatograph, conventionally, the eluate from the liquid chromatograph is split using a splitter, and only a small part is introduced into the electrostatic spray ion source. The way had been taken. However, it is difficult to operate a splitter with a separation ratio of 1: 100 stably,
The observed ionic strength was not stable either. Therefore, development of 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 has been desired.

FIG. 11 shows that the electrostatic spray ion source is operated at 200 rpm.
Solution in microliter (water / methanol / 5% acetic acid)
And the average diameter of the droplets in the jet 17 obtained by applying a voltage of 4 kV between the spray capillary 11 and the metal mesh 16 arranged at a position 15 mm away from the tip of the spray capillary, The results of examining the distribution of the number of particles are shown. The measurement was performed at a position 10 mm away from the tip of the spray capillary 11. Here, the number of particles means 0.
It represents the number of particles that passed through a space of 03 cubic millimeters. The central portion of the jet contains large diameter droplets generated by the pressure of the atomizing gas. These large droplets lower the temperature in the vicinity of the ion introduction pores and cause a reduction in ionic strength. On the other hand, as the distance from the center of the jet to the outer periphery increased, the average particle diameter of the droplet became smaller, and the particle diameter became constant at a distance of 3 mm or more from the center of the jet. Therefore, by taking in only the droplets having a small particle diameter existing in the outer peripheral portion of the jet from the ion introduction pore, the decrease in the ion intensity due to the cooling of the ion introduction pore can be reduced, and the ions can be observed stably. . SUMMARY OF THE INVENTION An object of the present invention is to provide an electrostatic spray ion source capable of intensely and stably capturing ionic strength, thereby realizing high sensitivity of a liquid chromatograph / mass spectrometer.

[0007]

In order to achieve the above object, that is, to obtain an electrostatic spray ion source capable of obtaining a stable 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 generating ions by electrostatic spray from the other end of the spray capillary;
In a mass spectrometer equipped with an ion introduction pore for introducing the generated ions into the vacuum section and a mass analysis section for mass analyzing the introduced ions, the tip of the spray capillary and the ion introduction pore A barrier is provided between the electrode and the opening to prevent the center of the jet from touching the periphery of the ion introduction pore. More specifically, 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 only the outer periphery of the jet to the periphery of the pore. In order to prevent the solution from accumulating in the barrier, a heating mechanism for evaporating the solution is provided independently of the other parts of the ion source, or the barrier is formed as a thread with an axial direction vector having 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 convergence of ions by the electric field, a mechanism is provided for applying a potential to the barrier independently of other portions of the ion source.

[0008]

A barrier is provided between the capillary for spraying the sample solution and the pore for taking in ions, so that the vicinity of the center of the jet containing large droplets does not come into contact with the periphery of the pore.
The decrease in the temperature of the pores can be reduced, so that the ion intensity can be stably observed in the mass spectrometer. In addition, the outer wall surface of the barrier is formed into a shape having a curvature, and a portion of the outer peripheral portion of the jet where a large amount of liquid droplets having a small particle size is obtained is converged to the ion introduction pore by an air current, whereby strong ion intensity can be obtained. it can. Therefore, a high-sensitivity mass spectrometer capable of stably observing ionic strength is possible.

[0009]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment according to the present invention will be described with reference to FIGS. FIG. 1 shows an electrostatic spray ion source according to a first embodiment of the present invention, in which a cross section of an electrostatic spray ion source in which a barrier is provided between the tip of a spray capillary and an opposing electrode having an opening for ion introduction is provided. FIG. The axis of the spray capillary 11 and the central axis of the ion intake pore are shifted from each other. The sample solution eluted from the liquid chromatograph is connected to the pipe 2, the connector 10
Is introduced into the spray capillary 11. Between the spraying capillary 11 and the counter electrode 12 where the ion introduction pore 15a opens,
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 flows from the spraying gas outlet 13. The charged droplets thus obtained are vaporized and ions are generated. The generated ions are supplied to the ion introduction pore 15
a, the gas is taken into the mass spectrometer 6 through the differential pumping section 19 and the ion introducing pore 15b. At this time, by providing the barrier 20a between the tip of the spray capillary 11 and the counter electrode 12, it is possible to prevent the vicinity of the center of the jet from touching the electrode, and to avoid a temperature change around the ion introduction pore 15a. Barrier 20a
Is preferably a conductor, but if the barrier of the conductor may disturb the electric field near the tip of the spray capillary, the barrier 20a may be made of an insulating material. 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 to vaporize the solution by heat.
Heating may be performed independently of other parts of the ion source. Further, the potential of the barrier 20 may be the same potential 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 barrier 20a uses a power supply 18b and is separated from the other parts of the ion source. A potential may be applied independently.
Further, even in the case of a configuration in which the central axis of the spray capillary 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 spray capillary and the central axis of the ion introduction pore are arranged at an angle, and the tip of the spray capillary and the ion introduction pore are arranged. FIG. 2 is a cross-sectional view of an electrostatic spray ion source in which a barrier is provided between a counter electrode and an opening. When the spray capillary is arranged at an angle to the central axis of the ion introduction pore, the vicinity of the center of the jet flow becomes
5a, and only the outer peripheral portion of the jet can be taken in from the ion introduction fine hole 15a, so that the ion intensity decreases due to the temperature change of the ion introduction fine hole 15a and the liquid on the surface of the counter electrode 12 The problem that the membrane closes the ion introduction pore 15a is reduced. However, with this configuration, it took about 10 minutes after the start of spraying until the temperature around the ion introduction pore reached temperature equilibrium. For this reason, there is a problem in performing the measurement quickly. Therefore, as shown in FIG.
By preventing the center portion of the jet from touching the counter electrode 12, the temperature of the counter electrode 12 can be kept constant at all times, and quick measurement has become possible. The second aspect of the present invention
In the embodiment of FIG. 3, in the case where the central axis of the spray capillary is arranged to be inclined with respect to the central axis of the ion introduction pore, FIG.
As shown in a cross-sectional view of an electrostatic spray ion source showing an example in which the direction of the barrier is changed, the direction of the barrier 20a may be changed.

FIG. 4 is a view showing a third embodiment of the present invention, in which an outer wall surface of a barrier has a curvature, and an electrostatic spray ion source for converging only an outer peripheral portion of a jet to an ion introducing pore. FIG. The shape of the barrier may be a plate shape or a block shape as shown in FIGS. 1 to 3, but as shown in FIG. 4, the outer wall surface of the barrier 20b has a curvature such as a circle, an ellipse, or a streamline, and the spray is formed. By controlling the flow of the application gas, large droplets at the center of the jet are applied to the barrier 20b to be eliminated, and only the portion of the outer periphery of the jet where many small droplets are obtained is ion-introduced. The light can be converged on 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 formed of a thread, a rod, or an aggregate thereof. As shown in FIG. 5, the barrier 20c may be composed of a thread or a rod arranged so that the axis direction vector has a component in the direction of gravity, or an aggregate thereof. With such a configuration, the solution accumulated in the barrier 20c flows down the thread or rod and flows away, so that it is possible to prevent the spray from becoming unstable. 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 a configuration provided with a mechanism for collecting a solution.
Shown in The solution sprayed from the ion source partially covers the barrier 2
At 0c, it flows down the thread or rod 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 collected by the collection container 22 is supplied to the photodetector 2
3 may be used for further analysis. Further, as described in FIG. 6, a solution flowing along a thread or a rod may be directly introduced into the photodetector 23. A mechanism for detecting the sample molecules and a mechanism for driving the barrier may be provided, and the barrier may be removed only when the sample molecules are 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 molecules can be analyzed, so that the temperature change of the pores and the contamination near the pores are reduced, and the amount of data stored in the data processing device is also small. I'm done.

FIG. 7 is a block diagram showing a fifth embodiment of the present invention, in which an 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 a light detector. 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 division by the splitter as shown in FIG. The signal from the photodetector is sent to the barrier 20d, the mass spectrometer, and the data processing device via the signal line 5c. In response to a signal from the photodetector, the barrier 20d is driven, and the mass analyzer 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 by the barrier 20d. When a signal from the photodetector is sent, the barrier is removed, ions are taken in from the ion introduction pore 15a, and at the same time, the mass spectrometer, the ion detector,
The data processing device 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 spraying method, but may include other spray ionization methods,
For example, it is also effective for atmospheric pressure chemical ionization, atmospheric pressure spray ionization, and the like.

[0014]

According to the present invention, it is possible to prevent a droplet having a large particle diameter from coming into contact with an electrode having an opening for ion introduction, among droplets generated by electrostatic spraying. Furthermore, by making the wall shape of the barrier have a curvature, only small droplets can be taken into the vacuum part from the ion taking pores. Therefore, the temperature of the ion intake pore does not change, and the ions can be stably and strongly observed in the mass spectrometer.

[Brief description of the 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 a barrier is changed in a 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 providing mass spectrometry by providing a mechanism for detecting a sample molecule 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 according to a fifth embodiment of the present invention.

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

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

FIG. 11 is a diagram showing a relationship between a distance from a jet center, an average particle diameter, and the number of droplets included in a 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 spectrometer, 7 ... Exhaust system, 8 ... Ion detector, 9 ... Data processing device, 10 ... Connector, 11 ... Spray tube, 12
··· Counter electrode, 13 · Spray gas outlet, 14 · Vaporizing gas outlet, 15, 15a, 15b · Ion-introduced pores, 1
6 ... metal mesh, 17 ... jet, 18a, 18b ... power supply, 19 ... differential exhaust part, 20a, 20b, 20c, 20
d: barrier, 21: heater, 22: collection container, 23: photodetector, 24: barrier support, 25: splitter.

──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Atsushi Maki 1-280 Higashi Koigakubo, Kokubunji-shi, Tokyo Inside the Central Research Laboratory of Hitachi, Ltd. (56) References JP-A-4-163849 (JP, A) JP-A-4-127050 (JP, A) JP-A-59-153164 (JP, A) (58) Fields investigated (Int. Cl ^7, DB name) G01N 27/62 -. 27/70 G01N 30/72 H01J 49/00 - 49/48

Claims (14)

(57) [Claims] 1. A sample solution fed from a liquid chromatograph is introduced into one end of the spray capillary, said by electrostatic spraying from the other end of the spray capillary and electrostatic spraying ion source for generating ions has the ion introduction aperture for introducing ions generated by the electrostatic spraying ion source vacuum unit
A counter electrode, a mass spectrometer for mass spectrometry of ions introduced into the vacuum section, and the other end of the spray capillary
And a arranged a barrier between the counter electrode, the barrier
Is a mass spectrometer provided with a heating means . 2. The mass spectrometer according to claim 1, wherein an outer surface of the barrier on the side of the spray capillary is flat. 3. The mass spectrometer according to claim 2, wherein said outer surface is inclined at a right angle or a desired angle with a central axis of said spray capillary. The outer contour of claim 4 wherein said barrier mass spectrometer as claimed in claim 1, characterized in that it has a curvature. Sectional shape according to claim 5, wherein the barrier is the mass spectrometer according to claim 1, characterized in that a circular, elliptical or aerodynamic. 6. A mass spectrometer as claimed in claim 1, wherein the barrier is a filamentous, rod-like or their aggregates. 7. A mass spectrometer as claimed in claim 6, characterized in that it comprises means for collecting or analyzing said sample solution from said barrier. 8. The apparatus according to claim 1, wherein a space between the counter electrode and the mass analyzer is provided.
An electrode in which a second ion introduction pore is formed is disposed, and a central axis of the spray capillary is the ion injection pore and the second axis.
The mass spectrometer according to any one of claims 1 to 7, wherein the mass spectrometer is parallel or inclined by a desired angle with a line connecting the centers of the ion introduction pores. 9. The mass spectrometer according to claim 8, wherein the ion introduction pore and the second ion introduction pore are formed in a portion other than a direction in which a central axis of the spray capillary extends. Total. 10. A protruding portion is formed on the spray tube side of the counter electrode, and the ion introduction pore is formed at a tip end of the protruding portion. 10. The mass spectrometer according to any one of claims 1 to 9. 11. The mass spectrometer according to claim 1, further comprising means for applying a desired potential to said barrier. 12. The mass spectrometer according to any one of claims 1 to 11, characterized in that it comprises means for applying a desired potential difference between the spray capillary and the counter electrode. 13. A spray capillary for electrostatically spraying a sample solution introduced into one end from the other end to generate a jet, and the other end on the other end side of the spray capillary. In a mass spectrometer including an ion introduction fine hole arranged at a predetermined interval and a mass spectrometer for analyzing ions extracted through the ion introduction fine hole, the other end portion and the ion introduction fine hole are provided. A mass spectrometer characterized in that a barrier is provided between the holes to block a central portion of the jet and pass through a desired outer peripheral portion, and the barrier includes a heating means. 14. The mass spectrometer according to claim 13, further comprising means for applying a desired potential to said barrier.