JP3350263B2 - Ion trap type 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 a liquid chromatography (Liquid Chromatogra
phy: LC) and mass spectrometry (MS)
, A device that combines
Mass Spectrometry (Liquid Chromatography / Mass Spectrometr
y, hereinafter referred to as LC / MS) or an apparatus using mass spectrometry as a detector for capillary electrophoresis (Capillary Electrophoresis), that is, Capillary Electrophoresis / Mass Spe
The present invention relates to an analyzer, such as typified by ctrometry (hereinafter abbreviated as CE / MS), which separates a mixed sample present in a liquid, ionizes the mixed sample, and introduces it into a mass spectrometer. The present invention also relates to a flow injection analyzer for continuously introducing a solution sample to perform ionization and mass spectrometry.

[0002]

2. Description of the Related Art In the field of analysis, LC / MS and C / C are currently used as new separation and analysis methods for volatile or nonvolatile compounds.
E / MS holds promise. For reference, FIG. 5 shows an LC / MS configuration using an ion trap mass spectrometer as described in Analytical Chemistry, 1991, Vol. 63, p. 375.

A sample in a solution eluted from the liquid chromatograph 1 is introduced into an LC / MS interface through a pipe 2. In an electrospray type atmospheric pressure ion source as shown in FIG. 5, the interface mainly comprises a metal capillary 5 to which a high voltage is applied. When a high voltage is applied to the metal capillary 5, the sample solution passing therethrough is electrostatically sprayed and changes into a charged droplet. At this time, a gas can be flowed from around the metal capillary 5 to promote spraying.

[0004] Ions related to the sample generated by this interface pass through the nozzle 6, the electrostatic lenses 38a and 38b in the differential pumping section, and the skimmer 8, and are introduced into the mass spectrometer under high vacuum. At this time, ions passing through the skimmer 8 are subjected to the end cap electrode 14a, the ring electrode 15, and the end cap electrode 14b by the electrostatic lenses 39a, 39b, and 39c having a convergence effect and a gate effect.
An end cap electrode 1 is installed in the ion trap mass spectrometer.
It is introduced from the ion intake port 16 provided in 4a.

[0005] Unlike other mass spectrometers, the ion trap type mass spectrometer uses a high frequency voltage to confine ions in the ion trap type mass spectrometer for a certain period of time, and then scans the high frequency voltage to perform ion trap mass spectrometry. An ion extraction port 17 for trapping ions trapped in the unit
And it is detected by the detector and the amplifier 37.

When ions are confined in the ion trap mass spectrometer, the movement of the ions is confined in both the z-axis direction (axial direction connecting the center of the end cap electrode) and the r-axis direction (diameter direction of the ring electrode). Performs harmonic vibration at a slower angular frequency while finely vibrating at a high frequency angular frequency. In order to efficiently extract the moving ions from the ion extraction port 17, the orbital amplitude of the ions must be reduced. Therefore, in an ion trap type mass spectrometer, helium gas is usually introduced into an ion trap type mass spectrometer, and the orbit amplitude is reduced by collision of ions with helium gas.

By the way, in the example of FIG. 5, helium gas is introduced into the entire chamber where the ion trap type mass spectrometer is present, so that the ion trap type mass spectrometer is filled with helium gas. The introduction amount of the helium gas is estimated based on the measurement result of an ion gauge which is a vacuum gauge provided in the chamber. Incidentally, in the example of literature, whereas the pressure in the chamber in the case of not introducing a helium gas is 1 × 10 ^-5 Torr, at the time of measurement, by introducing a helium gas, the pressure of the chamber 2-3 × 10 ^{- Three}
The measurement is performed with the pressure reduced to Torr. for reference,
FIG. 6 shows the relationship between the observed ion intensity and the pressure in the ion trap mass spectrometer. As can be easily understood from the result, the observed ion intensity is 10 ⁻³ Torr.
To 10 ^-4 Torr.

[0008] As described above, the ions mass-analyzed by the ion trap type mass spectrometer are detected by the detector, amplified, and transferred to the data processing device. In this data processing device, the obtained information is usually displayed as a mass spectrum.

[0009]

SUMMARY OF THE INVENTION In a conventional manner,
10 ^-3 to 10 ^-4 Torr in the ion trap mass spectrometer
Attempting to fill helium gas to a high pressure causes the following disadvantages. That is, (1) A large amount of helium gas having poor exhaust efficiency exists in the whole chamber, and a high vacuum (2-3 × 10 ⁻³⁾
(Torr or less) requires a vacuum pump having a high evacuation capacity, and at the same time places a heavy burden on the pump.

(2) When a detector such as an electron multiplier which needs to apply a high voltage (0-3 kV) under a not so good vacuum is operated, a high voltage is applied to the electron multiplier by discharge or the like. Ion trap type mass spectrometry, which increases the detection sensitivity by accumulating ions in the mass spectrometer, causing serious problems such as the inability to apply a voltage and high-sensitivity detection and shortening the life of the electron multiplier. It becomes impossible to take advantage of the total.

[0011]

In order to solve the above problems, in the apparatus of the present invention, an insulating material is fitted between two end cap electrodes and one ring electrode of an ion trap type mass spectrometer. In this way, the inside of the ion trap mass spectrometry unit is sufficiently closed, and the helium gas is directly introduced into the ion trap mass spectrometry unit from a helium gas supply source outside the vacuum through a pipe through the insulating material unit. According to the structure of the present invention, the diameter of the two end cap electrodes in the ion trap type mass spectrometer is one.
Since there is only an ion inlet and an ion outlet of about -2 mm, it is a kind of differential pumping state, and even if the pressure inside the ion trap electrode is in the order of 10 ^-3 to 10 ^-4 Torr, the chamber around the detector The internal pressure can be lower. Depending on the size of the exhaust system used, 200
If a turbo molecular pump of about 1 / sec is used, 10 ^-5
It is also possible to use a pressure in the order of -10 ^-6 Torr, and the pressure range can be set so that the detector can be operated sufficiently stably.

By the way, the pressure inside the ion trap type mass spectrometer is reduced by 10% because the orbit amplitude in the ion trap is reduced to increase the sensitivity.
Must be in the ^-3 to 10 ^-4 Torr range. Therefore, it is necessary to constantly monitor the pressure in the ion trap mass spectrometer. There are two ways to do this.

(1) A helium gas flow meter and a pressure gauge are provided in the middle of a path for introducing a helium gas from a helium gas supply source outside a vacuum, and the flow rate of the gas introduced into the ion trap mass analyzer is controlled. Estimate, from that value, consider the effective pumping speed in the ion trap mass spectrometer,
The pressure inside the ion trap type mass spectrometer is estimated.

(2) A vacuum gauge is provided on the end cap electrode, and the pressure in the ion trap type mass spectrometer is constantly monitored.

By using any of these methods, the pressure in the ion trap mass spectrometer can be constantly monitored, and in some cases, the flow rate of the helium gas flowing into the ion trap mass spectrometer can be controlled.

[0016]

According to the present invention, it is possible to sufficiently reduce the pressure in a region where a detector to which a high voltage needs to be applied is present. Becomes possible.

[0017]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the following description, a case where a liquid chromatograph is mainly used as a means for separating a mixed sample will be described, but it is also possible to use capillary electrophoresis for performing electrophoretic separation using a capillary tube. The same applies to flow injection analysis in which a sample solution is continuously introduced.

FIG. 1 shows an embodiment of the apparatus according to the present invention. The sample solution flowing out of the liquid chromatograph 1 is sent through a pipe 2 and a connector 3 to an electrospray-type atmospheric pressure ion source provided with a metal capillary 5, where charged droplets are generated. Here, an electrospray-type atmospheric pressure ion source utilizing the electrostatic spraying phenomenon in which charged droplets are directly generated has been shown. However, another atmospheric pressure ion source such as an atmospheric pressure chemical ionization method utilizing corona discharge with a needle electrode has been described. The same is true when (an ion source that generates ions under atmospheric pressure) is used.

The charged droplets generated by the electrospray type atmospheric pressure ion source are held by the first flange 7 and held by the nozzle 6 and the second flange 9 which are heated to a high temperature of 100 ° C. or higher by the heater 10a. In the process of passing through the skimmer 8 heated by the heater 10b, it is vaporized and generates ions. At this time, the first flange 7 and the second flange 9
Are electrically insulated from each other by insulating rings 11a and 11b, and a voltage is applied. Also,
A region surrounded by the first flange 7 and the second flange 9 is reduced from several tens Torr to 0.1 mm by a roughing vacuum pump 30. Number To
Exhausted to about rr.

After the ions that have passed through the skimmer 8 pass through electrostatic lenses 12a, 12b, and 12c having a convergence effect, a gate electrode 13 for controlling the ion implantation of ions into the ion trap mass analyzer is formed. After passing through, the ions are introduced from the ion intake port 16 into the ion trap type mass spectrometer surrounded by the end cap electrode 14a, the ring electrode 15, the end cap electrode 14b, and the two insulating rings 18a and 18b. Here, the ions trapped for a certain period of time are extracted to the outside of the ion trap type mass spectrometer by the scanning of the high frequency voltage through the ion extraction port 17 of the ion trap type mass spectrometer.

While ions are trapped in the ion trap type mass spectrometer, collision with helium gas is necessary to reduce the orbital amplitude. In FIG. 1, helium gas is introduced into the ion trap type mass spectrometer as follows.

Helium is first supplied from a helium gas supply source 28 such as a high-pressure cylinder via a pressure reducing valve 27 to a pipe 2.
6. The pipe 26 is usually made of stainless steel having an outer diameter of several mm. The piping 2
A needle valve 23, a helium gas flow meter 24, and a helium gas pressure gauge 25 are provided on 6, and the needle valve 23 adjusts the amount of helium gas supplied into the ion trap mass analyzer. By the way, it is practically impossible to supply helium gas using the needle valve 23 using a pipe having a large diameter of several mm so that the pressure in the ion trap type mass spectrometer becomes 10 ^-3 -10 ^-4 Torr. It is possible.

Therefore, a pipe having a small diameter is used in the path leading to the ion trap type mass spectrometer in order to reduce the conductance of the helium gas flow. In the example of FIG. 1, a fused silica capillary 22 coated with a polymer such as polyimide around an inner diameter of 0.25 mm and a length of 60 m follows a normal gas pipe 26 having a diameter of several mm. I have. The tip of the capillary 22 is fed into the ion trap mass analyzer via the capillary holder 21. As described above, if a capillary having a small diameter is introduced in the middle of the pipe leading to the ion trap mass spectrometer, the flow rate of helium gas at the helium gas flow meter 24 is 0-10 cc / min, Pressure of helium gas at pressure gauge 25 of 0-3kg
f / cm ^2, and the pressure inside the ion trap type mass spectrometer was set to 10 ⁻³ −10 ⁻⁴ To
It can be adjusted to rr.

By using a helium gas supply system, the pressure in the ion trap mass spectrometer can be easily estimated as follows.

Helium gas flow rate L just before the capillary
(M ³ / sec) and the pressure P ₀ (Pa) of the helium gas immediately before the capillary, the gas amount Q flowing into the ion trap mass spectrometer through the capillary 24 is: Q = LP · P ₀ (Pa · m) ³ / sec). Therefore, assuming that the effective pumping speed through the ion intake port 16 and the ion extraction port 17 of the two end cap electrodes is S (m ³ / sec), the pressure P ₁ (Pa) in the ion trap mass analyzer becomes Can be estimated as follows.

P ₁ = L · P ₀ / S (Pa) When the example of FIG. 1 is actually applied, the following is obtained. For example, the flow rate of helium gas immediately before the capillary is 0.5 ×
10 ⁻⁸ (m ³ / sec), and the helium gas pressure immediately before the capillary is 0.5 × 10 ⁵ (Pa). Using a turbo molecular pump with a pumping speed of helium gas of 0.2 (m ³ / sec), the ion intake port 16 and the ion extraction port 17 (both the diameter is 1.3 mm and the thickness is 0.3 mm) of the two end cap electrodes. 5m
Consider the case where the inside of the ion trap type mass spectrometer is evacuated via m).

At this time, the conductance C (m ³ / sec) in the ion trap type mass spectrometer is C = 2.121 · (1.3 × 10 ⁻³ ) ³ /(0.5×10 ³ )
⁻³ ) · √ (28.8 / 4.0) = 2.9 × 10 ⁻³ (m ³ / sec) Therefore, the effective pumping speed S in the ion trap mass spectrometer is approximately S = 2.9 × 10 ⁻³ (m ³ / sec). At this time, the pressure P ₁ (Pa) in the ion trap mass analyzer becomes P ₁ = 0.086 (Pa) = 6.5 × 10 ⁻⁴ (Torr). At this time, the pressure becomes lower than the pressure of the chamber around the ion trap mass spectrometer. The amount of gas flowing from the ion take-in port 9 and the ion take-out port 10 of the end cap electrodes 8a and 8b in the ion trap type mass spectrometer is approximately 2.5 × 10 ⁻⁴ (Pa · m ³ / sec). Since the amount of gas flowing from the skimmer 8 on the side of the atmospheric pressure ion source is on the order of 2 × 10 ⁻⁴ (Pa · m ³ / sec), the chamber pressure P ₂ is P ₂ = 2.3 × 10 ⁻³ (Pa). = 1.7 × 10 ⁻⁵ (Torr).

As described above, by adopting the structure according to the present invention, it is possible to keep the pressure difference between the pressure in the chamber and the pressure in the ion trap mass spectrometer at about two digits.
Of course, it is more preferable to actually attach the vacuum gauge to the end cap electrode of the ion trap mass spectrometer to calibrate the estimated value and the actual pressure with the value estimated as described above.

FIG. 2 shows a helium gas flow controller 3 instead of the needle valve 23 and the helium gas flow meter 24.
1 is used. When the helium gas flow controller 31 is linked to the data processing device 33, the pressure in the ion trap mass spectrometer can be kept constant, so that fluctuations in ion intensity can be suppressed.

FIG. 3 shows a case in which a vacuum gauge 34 is provided on the end cap electrode 14b in addition to the helium gas flow controller 31. Also in this case, the vacuum gauge 34, the helium gas flow controller 31 and the data processing device 33 can be linked.

Since a voltage is applied to the end cap electrode 14b, an insulating pipe 36 is required between the vacuum gauge 34 and the end cap electrode 14b as shown in FIG. Since it is necessary to prevent ions generated by a vacuum gauge such as a vacuum gauge from being introduced into the ion trap mass spectrometer, it is preferable to provide a plurality of meshes 35a and 35b made of a conductive material such as a metal in a passage. Good.

[0032]

According to the present invention, the pressure in the ion trap mass spectrometry section surrounded by the two end cap electrodes, one ring electrode, and the insulating material is reduced without reducing the pressure in the chamber where the detector is located. Required for high sensitivity
Since it can be kept in the range of 0 ^-3 to 10 ^-4 Torr, high-sensitivity analysis becomes possible.

[Brief description of the drawings]

FIG. 1 is a sectional view showing an embodiment of the apparatus of the present invention.

FIG. 2 is a sectional view showing an embodiment of the apparatus of the present invention.

FIG. 3 is a sectional view showing an embodiment of the apparatus of the present invention.

FIG. 4 is a sectional view showing a pressure gauge provided on an end cap electrode.

FIG. 5 is a configuration diagram of an apparatus according to a conventional technique.

FIG. 6 is a measurement diagram showing the relationship between the pressure inside the ion trap mass spectrometer and the observed ion intensity.

[Explanation of symbols]

1. Liquid chromatograph, 2. Piping, 3. Connector,
4: Electrospray type atmospheric pressure ion source, 5: metal capillary, 6: nozzle, 7: first flange, 8: skimmer, 9: second flange, 10a, 10b: heater, 11a, 11b: insulating ring, 12a , 12b, 12
c: an electrostatic lens having a convergence effect, 13: a gate electrode,
14a, 14b: end cap electrode, 15: ring electrode, 16: ion inlet, 17: ion outlet, 18a, 18b: insulating ring for ion trap mass analyzer, 19: converging lens, 20: detector, 21 ... Capillary holder, 22 ... fused silica capillary, 2
3 Needle valve, 24 Flow meter for helium gas, 2
5 ... helium gas pressure gauge, 26 ... helium gas pipe, 27 ... pressure reducing valve, 28 ... helium gas supply source, 29 ...
Vacuum pump for high vacuum, 30 ... Vacuum pump for roughing, 31
... helium gas flow controller, 32a, 32b, 32c ... signal line, 33 ... data processor, 34 ... vacuum gauge, 35
a, 35b: mesh, 36: insulating pipe, 37: detector and amplifier, 38a, 38b: electrostatic lenses in the differential exhaust section, 39a, 39b, 39c: electrostatic lenses having a convergence effect and a gate effect.

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-6-302295 (JP, A) JP-A-59-134546 (JP, A) JP-A-6-310091 (JP, A) (58) Field (Int.Cl. ⁷ , DB name) G01N 27/62-27/70 H01J 40/00-49/48

Claims (11)

(57) [Claims] 1. A means for generating ions under atmospheric pressure or a pressure equivalent thereto, a differential pumping section for introducing the ions into a high vacuum, and a mass pumping the ions introduced into the high vacuum. analysis, the mass spectrometer having an ion trap mass spectrometer unit for detecting, the ion trap
Opening in a space surrounded by two end cap electrodes, one ring electrode, and two insulating materials between the end cap electrode and the ring electrode forming the mold mass spectrometry unit , and the above-mentioned from a helium gas supply source outside vacuum. An ion trap type mass spectrometer characterized in that a path for introducing helium gas in a space is provided. To 2. A middle path for introducing the helium gas, a pressure gauge for helium gas, helium gas flow meter, and the needle valve according to claim 1, characterized in that provided at least one set Ion trap type mass spectrometer. 3. in the middle of the path for introducing the helium gas, a pressure gauge for the helium gas, the ion trap according to claim 1, helium gas flow control meter, characterized in that it is provided at least one set Mass spectrometer. 4. The ion trap mass spectrometer according to claim 3, characterized in that the helium gas flow control meter is controlled by the data processing device. 5. An end cap electrode opposite to the end cap electrode located on the differential pumping section side,
5. The ion trap mass spectrometer according to claim 4 , further comprising a vacuum gauge suitable for measuring a pressure range of 0 ^-2 to 10 ^-5 Torr. 6. The helium gas flow controller according to claim 5, wherein a signal of a vacuum gauge provided on said end cap electrode is read by a data processing device, and the flow controller for helium gas is controlled based on the result. 3. The ion trap mass spectrometer according to claim 1. 7. The ion trap mass spectrometer according to claim 5 , wherein a mesh exists between the end cap electrode provided with the vacuum gauge and the vacuum gauge . 8. The method according to claim 1, wherein the path for introducing the helium gas is formed by at least two kinds of pipes having different diameters, and a tip of a pipe having the smallest diameter is opened into the space. The ion trap type mass spectrometer described in the above. 9. The ion trap mass spectrometer according to claim 1, wherein a part of the path for introducing the helium gas is formed by a fused quartz capillary whose outside is covered with a polymer film. apparatus. 10. A helium gas pressure gauge and a helium gas flow meter or a helium gas flow controller are provided in the middle of a pipe having a larger diameter located upstream of the pipe having the smallest diameter. The ion trap mass spectrometer according to claim 8, wherein 11. and the helium gas pressure gauge, helium
Reading gas flow meter or a helium gas flow control meter, respectively 0-3kgf / cm ^2, the ion trap mass spectrometer according to claim 10, characterized in that the range of 0-10cc / min.