JPH10269985A - Mass spectrometer and mass spectroscopic method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To restrain neutral particles mixed into a mass separating, part and improve detection precision and analyse stably by ionizing a specimen under a substantial atmospheric pressure, generating a specimen ion, deflecting this specimen ion by an ion deflection electrode, and mass-separating the deflected specimen ion under a high vacuum and detecting it. SOLUTION: A solvent molecule is ionized by corona discharge due to high potential needle electrode together with a residual gas or the like. As a generated primary ion, a specimen molecule with its low ionization potential is ionized. All ion beams containing the generated specimen molecule collides with a neutral molecule, thereby forming a simple pseudo-molecule ion. An ion emitted from a second thin hole 14 is accelerated, decelerated, and converged by a lens system 16. For the converged ion beam, only an ion whose mass number meets conditions passes while vibrating the inside of a Q pole 17, and the Q pole 17 is passed as a mass separation beam.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a mass spectrometer and a mass spectrometry method, and more particularly to a liquid chromatograph / mass spectrometer direct-coupled spectrometer which is small and lightweight and suitable for automatic setting of analysis conditions. Regarding configuration and condition settings.

[0002]

2. Description of the Related Art A conventional apparatus uses corona discharge using a needle electrode as described in Japanese Patent No. 1136983 as an atmospheric pressure ionization method, and is used for analyzing gas molecules. No consideration was given to ionization.
Also, Analytical Chemistry No. 54, No. 1, (1
982) pages 143 to 146 (AnalitycalChemis
try, vol, 54, No. 11982 pp143-146)
Discusses the ionization method of liquid vaporization.

[0003]

When a sample is ionized at atmospheric pressure, a large amount of neutral particles are generated. When the neutral particles enter the mass separation unit, noise components increase due to contamination of the mass separation unit, and the detection accuracy decreases. Accordingly, stable operation is hindered.

[0004] Further, the above-mentioned prior art does not take into consideration the miniaturization of the apparatus and the automatic setting of analysis conditions, and has problems with installation conditions and operability.

[0005] It is an object of the present invention to provide a mass spectrometer and a mass spectrometry method capable of suppressing neutral particles mixed in a mass separation section, improving detection accuracy and performing stable analysis. The other purpose is to use a quadrupole mass spectrometer as the mass spectrometer, to reduce the size, to find parameters important for performance,
The purpose is to automatically set analysis conditions.

[0006]

In order to achieve the above object, according to the present invention, a sample is ionized in an ionization section at substantially atmospheric pressure to generate sample ions, and the sample ions generated in the ionization section are generated. The sample is deflected by an ion deflection electrode, and the sample ions deflected by the ion deflection electrode are mass-separated and detected under high vacuum.

Further, the above object is achieved by measuring analysis conditions combining characteristics of a quadrupole mass spectrometer and characteristics of an atmospheric pressure ionization method, finding the most important parameters, and automatically setting these parameters. Is done.

The neutral particles generated in the atmospheric pressure ionization section are removed by passing the neutral particles through an ion deflection electrode.

An atmospheric pressure ionization system having an intermediate pressure section is as follows.
The required ions can be emphasized by changing the energy of the ions running during this time. The quadrupole mass spectrometer is composed of four cylinders of about 20 cm in length and about 8 mm in outer diameter concentrically, applying high-frequency voltage and DC voltage under constant conditions, operating as a mass filter, and operating as an ionization chamber. Part is at low pressure and the ion energy incident on the quadrupole is 10 e
The V position has good characteristics (transmittance, resolution) as a mass spectrometer.

In the combination of the atmospheric pressure ionization having such characteristics and the quadrupole mass spectrometer, it has been experimentally revealed that the ion energy at the intermediate pressure section is an important factor for the characteristics of the apparatus.

Since the quadrupole mass spectrometer is arranged in a straight line from atmospheric pressure ionization to facilitate the alignment and determine the energy control voltage of the ions from the conditions of the liquid chromatograph, the best setting conditions are as follows. Easy to configure,
Installation conditions and operability are significantly improved.

[0012]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS One embodiment of the present invention will be described below with reference to FIG. In the liquid chromatograph (I) for separating the mixed solution for each component, methanol (CH ₃ OH), water (H ₂ O) or the like is used as the solvent 1 and pumped into the column 4 by the pump 2. When the mixed sample separated from the injector 3 is injected, the mixed sample is separated by the interaction with the column 4 and elutes sequentially with time.

The amount of the solution is too large to directly introduce the eluate containing the solvent 1 and the sample into the mass spectrometer, and it is impossible to ionize by the electron impact method using a general filament. This can be achieved by using an ionization method.

When the eluate is introduced into the atomizer 6 heated by the heater 7 through the microtube 5, the eluate becomes a vaporized jet and is atomized (II). Since the atomized droplets float as droplets adhering to the solvent, they are separated into the solvent and the sample molecules in the desolvation chamber 8 heated by the heater 9.

The solvent molecules are ionized (corresponding to primary ionization) together with the remaining gas (N ₂ ) by corona discharge with the needle electrode 10 having a high potential (5 to 10 kV). Since the generated primary ions are under atmospheric pressure, they collide with the sample one after another, and sample molecules having a low ionization potential are mainly ionized by charge transfer (atmospheric pressure ionization section II).
I). The generated ions are ejected from the first pores 11 to the intermediate pressure section IV exhausted by the oil rotary pump 24 or the like.
At this time, many cluster ions including sample ions are generated. Excess neutral molecules exit to the outside through the opening 12. By using such an atmospheric pressure ionization method, it is possible to directly ionize a large amount of eluent and sample molecules from a liquid chromatograph.

The total ion beam B mainly composed of the cluster ions including the sample molecules thus generated is physically dissociated by colliding with the neutral molecules existing in the intermediate pressure section IV, so that a simple ion beam B is obtained. Pseudo molecular ions (hydrogen addition ions, etc.). The degree of this dissociation can be controlled by changing the energy of the ions.
The voltage between the first pore 11 and the second pore 14 insulated by B23 is controlled by the drift power supply 29, and the target molecular ion amount is set to the maximum. The intermediate pressure section IV is surrounded by an insulated drift chamber 13 and is evacuated to about 10 Pa by oil rotary pumps R, P24 and the like.
The pressure is measured by Since the dissociation of the cluster ions depends on the number of collisions and the energy of the neutral molecule, the pressure and drift voltage of this portion are parameters for the target molecular ion. The ions that have exited the second pores 14 are efficiently extracted, accelerated, decelerated, and converged by the lens system 16. The convergent beam C at the converging section V is incident energy (about 10 eV) of ions to the next quadrupole mass analyzing section VI.
Can be decided. An ion energy incident on the quadrupole mass spectrometer of about 10 eV is a good condition in terms of ion transmittance and resolution, which corresponds to a field voltage difference between the drift chamber 13 and the Q pole 17. API ion source
In the experiment of the voltage difference between III, IV, and the converging portion V, the drift chamber 13 has good beam characteristics at about 120 V with respect to the ground, and the maximum ion beam amount can be obtained. For this reason, Q pole 1
In the atmospheric pressure ionization method, the field voltage of No. 7 is floated from the ground with respect to the normal ground potential, and the drift chamber 1
It was set about 10 eV lower than 3. Focused ion beam C
Means that only ions having a mass number satisfying the conditions pass while vibrating in the Q pole 17 and Q
The light passes through the pole 17. The mass separation beam D deflected by the deflection electrode 18 for removing neutral particles is amplified by the secondary electron multiplier 19, and detected and recorded as a mass spectrum by the detector 20. The mass separator VI is surrounded by a shield 21, and the housing 22 is evacuated to a high vacuum by an oil diffusion pump DP26 or the like. The introduction to the internal electrodes such as the Q pole 17 is performed from the flange 27. Drift power supply 2
9, lens power supply 30, drift chamber power supply 28, field power supply 34, Q-pole power supply 31, deflection power supply 32,
The secondary electron multiplier power supply 33 and the like are controlled by an overall control system 35 using a CPU.

In a liquid chromatograph / quadrupole analyzer system, it is important to detect ions of a sample component with high sensitivity (increase the amount of ions) as in a general analyzer. For this purpose, the alignment of the ion beam is important. In the present invention, the first pore 11, the second pore 14, the lens system 16, and the Q pole 17 are arranged in a straight line, and neutral particles are removed. S
In order to improve / N, the beam is deflected and detected. In the experiment, the energy-voltage (drift voltage) characteristics of the ions in the intermediate pressure section IV are the most effective as parameters. For the detection of an unknown sample, the pressure and the drift voltage are determined, for example, by guessing the solvent methanol (CH ₃ OH). It has been found that the conditions for maximum detection of molecular ions (CH ₃ OH.H ⁺ ) are good. Since there are beam intensity characteristics as shown in FIGS. 2A, 2B, and 2C, these conditions can be stored in the CPU overall control system 35 in advance and automatically set to the best point.

According to the present invention, efficient coupling between the atmospheric pressure ionization method and the quadrupole mass spectrometer and setting of conditions can be easily performed, and complicated conditions for the liquid chromatograph / quadrupole mass spectrometer can be set. It is performed automatically and operability is improved.

There are a wide variety of compounds to be analyzed by a liquid chromatograph / quadrupole mass spectrometer direct connection system, but the mass spectrum is composed of molecular ions reflecting molecular structure and cleavage ions. There are also cluster ions in which molecules are gathered. Their percentage depends on the energy of collisional dissociation, depending on the pressure of the system and the energy of the ions,
Experiments have shown that, although often giving complex spectra, the instrument settings can be set, for example, by the mass spectrum of methanol, which is most often used as a solvent. That is, the pseudo-molecular ion of methanol (CH ₃ OH
H ⁺ , mass number 33) and cleavage ion (CH ₃ ⁺ , mass number 15)
The ratio of both ions 9 is preferably in the range of 10: 1 to 10:10.

Further, the cleavage ions (C ⁺ , CH ⁺ , C
If there are many ions such as H ₂ ⁺ and mass numbers 12, 13, 14), it indicates that cleavage is in progress.

While displaying these peaks on the CRT screen in real time, the ion energy control voltage and the lens voltage are automatically set to a point where the peak intensity of CH ₃ OH · H ⁺ is large according to the pressure of the intermediate pressure chamber. A mass spectrum by atmospheric pressure ionization with good reproducibility can be obtained. FIG.
FIG. 3 shows an example of a mass spectrum with respect to the energy control voltage (drift voltage) of methanol ions. The setting value is preferably a condition as shown in FIG.

When detecting a small amount of sample ions, depending on the conditions of the drift voltage, such as the flow rate of the liquid chromatograph, the temperature of the desolvation chamber, the pressure of the intermediate pressure chamber, etc., rectilinear movement caused by collision of ions with neutral particles. Neutral particles may be incident on the quadrupole mass spectrometer and lower the detection limit. In this case, providing an ion deflection electrode in front of the quadrupole analyzer so as not to capture neutral particles is effective in improving the ion detection limit,
FIG. 4 shows an example of the arrangement.

According to the present embodiment, there is an effect of improving the operability in which conditions can be easily set as a small-sized liquid chromatograph / quadrupole mass spectrometer.

[0024]

As described above, according to the present invention,
Accuracy and stability can be improved. According to another aspect of the invention, the following effects can be obtained.

(1) Since the atmospheric pressure ionization section, lens section, and Q pole section are arranged in a straight line, axis alignment is easy, and performance reproducibility can be maintained even during cleaning, reassembly, and the like.

(2) Since the Q-pole potential is raised to the potential of the intermediate pressure section, the ion beam can be handled with high energy, and the loss of ions having a large mass number is small.

(3) Since the drift voltage as a parameter of the amount of ions is used for setting conditions, it is easy to set conditions for unknown samples. Further, the pressure of the intermediate pressure section is also an important parameter, and these are also used for setting the conditions.

With the above effects, the liquid chromatograph / quadrupole mass spectrometer direct connection system can be used as a small dedicated machine or as a highly operable device.

[Brief description of the drawings]

FIG. 1 is a schematic diagram of one embodiment of the present invention.

2 (A) and 2 (B) are diagrams showing beam amount characteristics with respect to a drift voltage and a flow rate of a liquid chromatograph, respectively, and FIG.
FIG. 5 is a graph showing ion transmittance and resolution characteristics with respect to a field voltage of a pole.

FIG. 3 shows a mass spectrum of methanol.

FIG. 4 is an ion beam deflection arrangement diagram.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Solvent, 2 ... Pump, 3 ... Injector, 4 ... Column, 5 ... Microtube, 6 ... Atomizer, 7 ... Heater, 8 ... Desolvation chamber, 9 ... Heater, 10 ... Needle electrode, 11
... 1st pore, 12 ... opening, 13 ... drift chamber,
14: second pore, 15: insulator A, 16: lens system, 1
7 Q pole, 18 deflection electrode, 19 secondary electron multiplier, 20 detector, 21 shield, 22 housing, 23 insulator B, 24 oil rotary pump, 25 pressure gauge, 26 ... Oil diffusion pump, 27 ... Flange, 28 ... Drift chamber power supply, 29 ... Drift power supply, 30 ... Lens power supply, 31 ... Q pole power supply, 32 ... Deflection electrode power supply, 3
3: Secondary electron multiplier power supply, 34: Field power supply, 35
... CPU overall control system, 36 ... CRT, A: atomized droplet beam, B: all ion beam, C: convergent beam, D ...
Mass separation beam, I: liquid chromatograph section, II: atomization section, III: atmospheric pressure ionization section, IV: intermediate pressure section, V: converging section, VI: quadrupole mass separation section.

Claims (14)

[Claims] 1. An atmospheric pressure ion section for ionizing a sample under substantially atmospheric pressure to generate sample ions, separation detecting means for detecting the sample ions by mass separation under a high vacuum, and detecting the ionized section. A mass spectrometer comprising an ion deflection electrode provided between the separation and detection means. 2. A means (atomizer) for jetting a separated eluate from a liquid chromatograph through a heated pore, and heating the atomized and solvated sample component according to claim 1. The ionization unit includes primary ionization by a colon discharge of the needle electrode under atmospheric pressure, and means for performing secondary ionization by a subsequent ion-molecule reaction, Further, means for guiding generated ions to an intermediate pressure chamber lower than the atmospheric pressure from the first pores to exhaust neutral molecules and to control ion energy by collision with remaining neutral molecules and an electric field. To obtain a pseudo molecular ion of the sample molecule,
Focusing means consisting of ion extraction acceleration and deceleration electrodes for guiding ions from the pores to the mass spectrometer are provided, these are arranged in a straight line, and the separation and detection means is a direct-coupled quadrupole mass spectrometer. A mass spectrometer characterized by comprising: 3. The method according to claim 2, wherein the potential of the intermediate pressure section is set to 100 eV or more, and the field voltage of the quadrupole mass spectrometer is set to 5 eV or less in conjunction with the potential of the intermediate pressure section. Mass spectrometer characterized by performing. 4. The means according to claim 2, wherein the energy control voltage of the ions in the intermediate pressure chamber is detected by detecting the pressure in the intermediate pressure chamber, and the energy control voltage of the ions is set manually or automatically in conjunction with the pressure. A mass spectrometer characterized by comprising: 5. The method according to claim 2, wherein the energy control voltage of the ions in the intermediate pressure chamber is changed to the ion of a separation solvent in a liquid chromatograph, for example, in the case of methanol, the pseudo-molecular ion (CH ₃ OH.H ⁺ , Mass number 33), and automatically sets the peak value to a maximum value. 6. The ion energy of the intermediate pressure chamber according to claim 2, wherein a set condition of a solvent flow rate of the liquid chromatograph, a temperature of an atomizer and a temperature of a desolvation chamber is stored in advance. A mass spectrometer characterized by automatically setting a control voltage. 7. The method according to claim 5, wherein, for example, in the case of methanol, a pseudo molecular ion (CH ₃ OH.
H ⁺ , mass number 33) and decomposition ions (CH ₃ ⁺ , mass number 1)
5), and the ratio of both ions is 10: 1 to 1
A mass spectrometer, wherein the ion energy control voltage is set to be between 0:10. 8. The method according to claim 2, wherein the energy control voltage of the ions in the intermediate pressure chamber and the voltage of the lens system at the front stage of the quadrupole mass spectrometer are determined by the intensity of a specific ion, for example, the peak of the mass 33 of methanol. A mass spectrometer characterized in that the energy control voltage and the lens voltage are combined and set so that is maximized. 9. A quadrupole mass spectrometer according to claim 2, wherein an ion beam deflection electrode is provided after the atmospheric pressure ionization unit and before the quadrupole analyzer. A mass spectrometer characterized by being arranged so as to prevent it. 10. The ion energy control voltage of the intermediate pressure chamber and the lens voltage while simultaneously displaying a plurality of peaks on a CRT screen or the like, for setting a plurality of peak intensities. Mass spectrometer, wherein the voltage is set to an optimum voltage. 11. The method according to claim 1, wherein a first ion beam is provided between the atmospheric pressure ionization section and the ion deflection electrode so that sample ions generated by the atmospheric pressure ionization section pass therethrough.
And a second opening provided between the ion deflecting electrode and the separation / detection means so that sample ions passing through the ion deflecting electrode pass therethrough. The mass spectrometer, wherein axes of the second openings are not coincident. 12. The mass spectrometer according to claim 11, further comprising atomizing means for atomizing a liquid containing the sample, wherein the sample is ionized by the atmospheric pressure ionization section. 13. An intermediate pressure section between the atmospheric pressure ionization section and the separation detecting means, wherein the intermediate pressure section is maintained at a pressure between atmospheric pressure and the pressure of the separation detecting means. A first electrode and a second electrode arranged so as to sandwich at least a part of the portion, and voltage applying means for applying a voltage between the first electrode and the second electrode. Mass spectrometer. 14. A sample ionized by an ionization section under substantially atmospheric pressure to generate sample ions, the sample ions generated by the ionization section are deflected by an ion deflection electrode, and the sample deflected by the ion deflection electrode. A mass spectrometric method comprising detecting ions by mass separation under high vacuum.