JPH02181645A - Direct coupling device for liquid chromatograph and mass spectrometer - Google Patents

Abstract

PURPOSE:To miniaturize the device and to allow automatic setting of analysis conditions by measuring the analysis conditions combining the characteristics of the tetrode type mass spectrometer and the characteristics of an atm. ionization system and finding out the most important parameter. CONSTITUTION:The separated eluent from liquid chromatograph is heated by heaters 7, 9 and passes through a fine hole 5 by which the eluent is atomized and the solvent component is removed. This eluent is subjected to the primary ionization by the corona discharge of a needle electrode 10 of a high potential under the atm. pressure then to the secondary ionization by ion molecular reaction. The generated ions are introduced from a 1st fine hole 1 into an intermediate pressure chamber IV to discharge the neutral molecules. A converting means V consisting of the electrode which controls the energy to obtain the pseudo molecule ions of the sample molecules, draws the ions out of a 2nd fine hole 14 and accelerates and decelerates the ions is disposed on one straight line and is directly coupled to the tetrode type mass spectrometer VI. The intricate condition setting of the device I and the device VI is automatically executed in this way and the operability is improved.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a liquid chromatograph/mass spectrometer direct-coupled analysis device, and in particular to the configuration and condition setting of a device that is small and lightweight and suitable for automatically setting one analysis condition. Regarding.

[Conventional technology]

The conventional device is Patent No. 113 as an atmospheric pressure ionization method.
As described in No. 6983, this method utilizes corona discharge using a needle electrode, and is used for analyzing gas molecules, without considering the ionization of liquid. Also, Analyte Chemistry No. 54, Nα1. (1982) pp. 143-146 (Analytical C
hemistry, vol, 54, Ha1198
2 Pp143-146) discusses the ionization method of liquid vaporization.

[Problem to be solved by the invention]

The above-mentioned conventional technology does not give consideration to miniaturization of the apparatus and automatic setting of analysis conditions, and there are problems with installation conditions and operability.

The purpose of the present invention is to miniaturize the mass spectrometer by using a quadruple horizontal mass spectrometer, and to discover parameters important for performance.
The goal is to automatically set analysis conditions.

[Means to solve the problem]

The above objective is achieved by measuring analysis conditions that combine the characteristics of the quadruple horizontal mass spectrometer and the characteristics of the atmospheric pressure ionization method, finding the most important parameters, and automatically setting them.

C effect] The atmospheric pressure ionization method having an intermediate pressure section can emphasize desired ions by changing the energy of the ions running between the sections. In addition, the quadruple horizontal mass spectrometer combines four cylinders with a length of about 20 am and an outer diameter of about 8 m in a concentric circle, and applies high frequency voltage and DC voltage under certain conditions.
The characteristics (transmittance, resolution) as a mass spectrometer are good when the device is operated as a mass filter, the ionization chamber is kept at a low pressure, and the ion energy incident on the quadrupole is about 10 eV.

Experiments have revealed that when combining atmospheric pressure ionization with such characteristics and a quadrupole mass spectrometer, the energy of ions in the intermediate pressure section is an important factor in determining the characteristics of the device.

In the present invention, the quadrupole mass spectrometer is arranged in a straight line from atmospheric pressure ionization to facilitate axis alignment, and the ion energy control voltage is determined from the liquid chromatograph conditions, so the best setting conditions are Easy to set up, significantly improving installation conditions and operability.

〔Example〕

An embodiment of the present invention will be described below with reference to FIG. Liquid chromatograph CI), which separates a mixed solution into components, is
Solvent 1 such as methanol (CHa○H) or water (H2O)
and pumped into column 4 by pump 2. When a mixed sample to be separated is injected from the injector 3, the mixed sample is separated due to interaction with the column 4 and elutes sequentially over time.

The volume of the eluate containing solvent 1 and the sample is too large to introduce directly into the mass spectrometer, and it is impossible to ionize it using the electron impact method using a general filament, but the atmospheric pressure ionization method It becomes possible if you use it.

When the eluate passes through the microtube 5 and is guided to the atomizer 6 heated by the heater 7, the eluate becomes a vaporized jet.
Atomized (n). Since the atomized droplets float as a liquid layer adhering to the solvent, they are separated into the solvent and sample molecules in the desolvation chamber 8 heated by the heater (2) 9.

Solvent molecules, together with residual gas (N2) etc., are exposed to high potential (
5 to 10 kV) by corona discharge from the needle electrode 10 (-secondary ionization). Since the generated primary ions are under atmospheric pressure, they collide with the sample etc. one after another, and mainly sample molecules with low ionization potential are ionized due to charge transfer etc. (atmospheric pressure ionization section m). The generated ions are ejected from the first pore 11 to the intermediate pressure section (2) which is exhausted by an 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 air through the opening 12. By using such an atmospheric pressure ionization method, it becomes possible to directly ionize a large amount of eluent and sample molecules from a liquid chromatograph.

The total ion beam ■, which is mainly composed of cluster ions containing four sample molecules, is physically dissociated by colliding with the neutral molecules present in the intermediate pressure region ■, and becomes simple pseudomolecules. It becomes an ion (hydrogenated ion, etc.).

The degree of this dissociation can be controlled by changing the energy of the ions, and the insulator A15. The voltage between the first pore 11 and the second pore 14, which are insulated by B23, is controlled by a drift power supply 29, and the target molecular ion amount is set to be maximum. This intermediate pressure section (■) is surrounded by an insulated drift chamber 13, and oil rotary pumps R, P24
etc., to a pressure of about 10 Pa, and the pressure is measured with a pressure gauge 25. Since the dissociation of cluster ions depends on the number and energy of collisions with neutral molecules, the pressure and drift voltage of this part are the parameters for the target molecular ion. The ions exiting the second pore 14 are efficiently extracted by the lens system 16, accelerated, decelerated, and focused. The convergent beam C at this converging section V can determine the incident energy (about loeV) of ions to the next quadrupole mass spectrometer section (2). The incident ion energy to the quadrupole mass spectrometer is 10
About eV is a good condition in terms of ion transmittance and resolution, and this corresponds to the field voltage difference between the drift chamber 13 and the Q ball 17. API ion source ■.

(2) In an experiment regarding the voltage difference on the converging section, 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.

The field voltage of Q pole 17 is normally set to ground potential,
In the atmospheric pressure ionization method, the chamber was floated above the ground and set approximately 1 oeV lower than the drift chamber 13. While the focused ion beam C vibrates within the Q-ball 17, only ions having a mass number that satisfies the conditions pass through the Q-pole 17 as a mass-separated beam D. A mass-separated beam D deflected by a deflection electrode 18 for removing neutral particles is amplified by a secondary electron multiplier 19, and detected and recorded as a mass spectrum by a detector 20.

The mass separator ■ is surrounded by a shield 21 and a housing 22
is exhausted into the air by an oil diffusion pump DP26 or the like. It is introduced from the flange 27 into an internal electrode such as the Q pole 17. The control system includes a drift power supply 29, a lens power supply 30, a drift chamber power supply 28, and a field power supply 3.
4. Q pole power supply 31. A deflection power source 32, a secondary electron multiplier tube power source 33, and the like are controlled by an overall control system 35 using a CPU.

In liquid chromatograph/quadrupole analyzer systems as well as in general analyzers, it is important to detect sample component ions with high sensitivity (large ion amount). For this purpose, alignment of the ion beam is important, and in the present invention, the first pore 11, second pore 14, lens system 16, and Q ball 17 are arranged in a straight line, and neutral particles are removed. In order to improve the S/N, the beam is deflected and detected. In addition, in the experiment, the ion energy voltage (
Drift voltage) characteristics are the most effective parameters,
For detection of unknown samples, the pressure and drift voltage can be adjusted, for example, by using pseudomolecular ions (CH3
It has been found that the conditions for maximum detection of OH・HH+) are good. Since there are beam intensity characteristics as shown in Figure 2 A, B, and C, these conditions can be stored in advance in the CPU overall control system 35 and automatically set to the best point. .

According to the present invention, efficient coupling and condition settings between the atmospheric pressure ionization method and a quadrupole mass spectrometer can be easily achieved, and complex condition settings for liquid chromatographs and quadrupole mass spectrometers can be automatically performed. This improves operability.

A wide variety of compounds are analyzed using a liquid chromatograph/quadrupole mass spectrometer direct connection system, and their mass spectra consist of molecular ions and cleavage ions that reflect the molecular structure. There are also cluster ions in which molecules gather together. These ratios depend on the energy of collisional dissociation due to the pressure of the system and the energy of the ions, and often give complex spectra. However, it is possible to set the instrument setting conditions, for example, based on the mass spectrum of methanol, which is the most commonly used solvent. Confirmed by experiment.

That is, the pseudomolecular ion of methanol (C)IsOH-
H + mass number 33) and cleavage ion (CHa 0 mass number 15)
The ratio of both ions is preferably in the range of 10:1 to 10:10.

Furthermore, cleavage ions (C+, CH,, CHz+mass number 1
A large number of ions such as 2.13.14) indicates that cleavage is progressing.

While displaying these peaks in real time on the CRT screen, the ion energy control voltage and lens voltage are automatically set to the point where the peak intensity of C) I3OH・H−H+ is large according to the pressure in the intermediate pressure chamber. Mass spectra with high atmospheric pressure ionization can be obtained. FIG. 3 shows an example of a mass spectrum with respect to the energy control voltage (drift voltage) of methanol ions. The setting values are preferably as shown in FIG. 3a.

When detecting ions in a small amount of sample, depending on the flow rate of the liquid chromatograph, the temperature of the desolvation chamber, the pressure of the intermediate pressure chamber, etc., and the drift voltage conditions, straight-travel neutrality generated by collision between ions and neutral particles may occur. If there are many particles that may enter the quadrupole mass spectrometer and lower the detection limit, an ion deflection electrode should be installed in front of the quadrupole mass spectrometer to prevent neutral particles from being taken in. This arrangement is effective in improving the detection limit of ions, and an example of its arrangement is shown in FIG.

According to this embodiment, the operability of the compact liquid chromatograph/quadrupole mass spectrometer is improved by making it easy to set conditions.

〔Effect of the invention〕

According to the present invention, there are the following effects.

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

(2) Since the Q ball potential is raised to the potential of the intermediate pressure section, the ion beam can be treated with high energy, so there is less loss of ions with large mass numbers.

(3) Since the drift voltage as a parameter of ion amount is used for setting conditions, it is easy to set conditions for unknown samples. Furthermore, since the pressure in the intermediate pressure section is also an important parameter, it is also used for setting conditions.

With the above-mentioned 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] Figure 1 is a schematic diagram of an embodiment of the present invention, Figure 2 (A), (
B) is a beam amount characteristic diagram with respect to drift voltage and liquid chromatograph flow rate, (C) is a diagram showing ion transmittance and resolution characteristic diagram with respect to Q ball field voltage, Figure 3 is a diagram showing the mass spectrum of methanol, and Figure 4 is a diagram showing the mass spectrum of methanol. The figure shows an ion beam deflection arrangement. 1...Solvent, 2...Pump, 3...Injector, 4...Column, 5...Microtube, 6...
・Atomizer, 7... Heater ■, 8... Desolvation chamber, 9...
・Heater ■, 1°...needle electrode, 11...first pore,
12... Opening, 13... Drift chamber, 14
...Second narrow direction, 15...Insulator A, 16...Lens system, 17...Q Ho) I, r, 18... Deflection electrode, 19...Secondary electron multiplication tube, 2o...detector,
21... Shield, 22... Housing, 23...
・Insulator B, 24... Oil rotary pump, 25... Pressure gauge, 26... Oil diffusion pump, 27... Flange, 2
8... Drift chamber power supply, 29... Drift power supply, 3°... Lens power supply, 31... Q ball power supply,
32... Deflection electrode power supply, 33... Secondary electron multiplier tube 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...Tube separation beam, ■...Liquid chromatograph section, ■...Atomization section, ■...Atmospheric pressure ionization section, ■...
・Intermediate pressure section, ■... Convergence section, ■... Quadrupole mass separation section. 2nd cause Figure 1 (A') I''S7 Toden/E (5) Clothes! (C) Field t, L

Claims (1)

[Claims] 1. A means (atomizer) for jet atomizing the separated eluate from a liquid chromatograph through heated pores, and heating the atomized and solvated sample components to remove the solvent components. (a desolvation chamber), a means for primary ionization by corona discharge of a needle electrode under atmospheric pressure, and a means for secondary ionization by subsequent ion-molecule reaction; , into an intermediate pressure chamber lower than atmospheric pressure,
In addition to exhausting neutral molecules, a means is provided to control the energy of ions caused by collisions with remaining neutral molecules and an electric field, mainly to obtain quasi-molecular ions of sample molecules, and the ions are mass-analyzed from a second pore. A liquid chromatograph/mass spectrometer direct connection device, characterized in that a convergence means consisting of acceleration and deceleration electrodes for extracting ions is provided, these are arranged in a straight line, and directly connected to a quadrupole mass spectrometer. . 2. Setting the potential of the intermediate pressure section to 100 eV or more,
Further, the field voltage of the quadrupole mass spectrometer is linked to the potential of the intermediate pressure section and is set to be lower than 5 eV. Device. 3. The ion energy control voltage in the intermediate pressure chamber is characterized by being provided with means for detecting the pressure in the intermediate pressure chamber and manually or automatically setting the ion energy control voltage in conjunction with the pressure. Claim 1
A device directly connected to a liquid chromatograph/mass spectrometer as described in Section 1. 4. The ion energy control voltage in the intermediate pressure chamber is used to detect the peak of the ion of the separation solvent solution of the liquid chromatograph, for example, in the case of methanol, the pseudomolecular ion (CH_3OH・H^+, mass number 33) of the protonated ion. The liquid chromatograph/mass spectrometer direct connection apparatus according to claim 1, wherein the liquid chromatograph/mass spectrometer direct connection apparatus is characterized in that the maximum value is automatically set. 5. Automatically setting the ion energy control voltage in the intermediate pressure chamber based on pre-stored conditions of the solvent flow rate of the liquid chromatograph, the temperature of the atomizer, and the desolvation chamber. A liquid chromatograph/mass spectrometer direct connection device according to claim 1, characterized in that: 6. In the apparatus according to claim 4, for example, in the case of methanol, pseudomolecular ions (CH_3OH・H^+, mass number 33) of protonated ions and decomposed ions (
A liquid chromatograph/mass spectrometer characterized by detecting the peak of CH_3^+, mass number 15) and setting the ion energy control voltage so that the ratio of both ions is between 10:1 and 10:10. Direct connection device. 7. Energy control of the ion energy control voltage in the intermediate pressure chamber and the voltage of the lens system at the front stage of the quadrupole mass spectrometer so that the intensity of a specific ion, for example, the peak of the mass 33 of methanol, is maximized. 2. The liquid chromatograph/mass spectrometer direct connection device according to claim 1, wherein the voltage and lens voltage are set in combination. 8. The ion beam is constituted by the means described in claim 1, and an ion beam deflection electrode is provided after the atmospheric pressure ionization section and before the quadrupole analyzer section, and the ion beam goes straight to the quadrupole mass spectrometer. A system directly connected to a liquid chromatograph/quadrupole mass spectrometer, which is characterized by its arrangement to prevent neutral particles from entering. 9. To set a plurality of peak intensities as set forth in claim 6 or 7, while displaying a plurality of peaks simultaneously on a CRT screen, etc., the ion energy control voltage of the intermediate pressure chamber and the lens are set. A device directly connected to a liquid chromatograph/mass spectrometer that is characterized by interlocking the voltages and setting the optimal voltage.