JP3596375B2 - Atmospheric pressure ionization mass spectrometer - Google Patents

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for analyzing a sample in a substantially atmospheric pressure atmosphere, such as an electrospray mass spectrometer (ESP-MS), an atmospheric pressure chemical ionization mass spectrometer (APCI-MS), and a high frequency inductively coupled plasma mass spectrometer (ICP-MS). The present invention relates to an atmospheric pressure ionization mass spectrometer (API-MS) for ionization.
[0002]
[Prior art]
When a mass spectrometer (hereinafter abbreviated as “MS”) is used as a detector of a high-performance liquid chromatograph (hereinafter abbreviated as “LC”), ions generated by ionization such as an electrospray method and an atmospheric pressure chemical ionization method are used. An ionization interface is used which introduces into the mass spectrometer. In general, such an ionization method hardly causes fragmentation of ions, and relatively large numbers of molecular ions are generated due to one or more electrons jumping out of the original molecule. Therefore, the mass spectrum obtained by such analysis is very useful for estimating the molecular weight of the target component. On the other hand, since fragment ions (cleavage ions) associated with cleavage are small, they are not suitable for estimating the structure of a compound.
[0003]
[Problems to be solved by the invention]
MS / MS is suitable for such purposes as structural analysis of the compound. In the MS / MS, the ions selected by the first stage MS are introduced into a collision reaction chamber (analysis chamber), where they are collided with gas molecules to promote the fragmentation of the ions. Measured by MS. However, the conventional MS / MS has a disadvantage that the device itself becomes large and expensive.
[0004]
On the other hand, an attempt has been made to simply perform collision activation dissociation (Collision Activation Dissociation = CAD) in the conventional MS configuration. That is, a high voltage of about 80 to 200 V is applied to a deflector electrode provided in a vacuum chamber having a relatively high pressure (that is, a large amount of residual gas molecules) to accelerate the fragmentation of ions by collision with the residual gas molecules. Things. However, when a plurality of components are ionized almost simultaneously, there is a problem that peaks due to various fragment ions of the plurality of components appear in a mass spectrum, which makes structural analysis and the like extremely difficult.
[0005]
The present invention has been made in view of such a point, and an object of the present invention is to perform collision-activated dissociation analysis of preselected ions in the same manner as MS / MS, and at the same time, to be small and inexpensive. Atmospheric pressure ionization mass spectrometer.
[0006]
[Means for Solving the Problems]
The present invention has been made to solve the above-mentioned problems. The present invention provides a plurality of ionization chambers which are substantially at atmospheric pressure and an analysis chamber which is in a high vacuum atmosphere and has a mass spectrometer. Atmospheric pressure ionization mass spectrometer of a multi-stage differential exhaust system having an intermediate vacuum chamber of
a) provided in a first intermediate vacuum chamber maintained in a low vacuum atmosphere at the next stage of the ionization chamber, including a first multipole lens including a virtual rod electrode;
b) the virtual rod electrode comprises an envelope of a plurality of electrode plates separated from each other in the ion optical axis direction,
c) the ion passage space surrounded by the electrode plate is configured to gradually narrow as it proceeds in the ion traveling direction;
d) With respect to the virtual rod electrode of the first multipole lens, a voltage obtained by superimposing a DC voltage and a high-frequency voltage, whose polarity is inverted between adjacent electrodes and has a voltage value corresponding to the mass number of the target ion. Voltage applying means for applying
e) disposed in a second intermediate vacuum chamber subsequent to the first intermediate vacuum chamber and maintained in a medium vacuum atmosphere, and applied with a voltage obtained by superimposing a high-frequency voltage and a DC voltage to promote cleavage of passing ions. A second multipole lens,
In addition, the target ions are selected by the first multipole lens in the first intermediate vacuum chamber, the cleavage of the target ions is promoted in the second intermediate vacuum chamber, and various ions generated thereby are introduced into the mass spectrometer. Features.
[0007]
Here, the virtual rod electrode is composed of a plurality of electrode plates separated from each other in the ion optical axis direction, and the envelope of the electrode plate corresponds to the rod electrode. The configuration of such a multipole lens has already been proposed by the present applicant in Japanese Patent Application No. 11-196856. The second multipole lens may be a plurality of rod electrodes as in the case of the first multipole lens, or may be a plurality of plate-like electrodes provided with the ion optical axis interposed therebetween.
[0008]
BEST MODE FOR CARRYING OUT THE INVENTION
In the atmospheric pressure ionization mass spectrometer of the multistage differential exhaust system as in the present invention, conventionally, a ring-shaped or plate-shaped electrode opposed to each other with an ion optical axis interposed therebetween is provided in a first intermediate vacuum chamber next to the ionization chamber. An ion lens was provided. The main purpose of these ion lenses is to converge the ions introduced into the first intermediate vacuum chamber and efficiently send them into the second intermediate vacuum chamber. On the other hand, in the atmospheric pressure ionization mass spectrometer according to the present invention, the first multipole lens having the function of selecting ions according to the mass number is used instead of the conventional ion lens that only performed the function of converging ions. Is provided in the first intermediate vacuum chamber.
[0009]
The first multipole lens has an operation and a function similar to those of a quadrupole mass filter used as a mass analyzer. When a voltage is applied by the voltage applying means, an electric field generated thereby is generated. Converges only ions having a specific mass number to the rear focal position and diverges other ions. Since the first intermediate vacuum chamber has a low degree of vacuum and many residual gas molecules, the ion selectivity is not as high as that of the quadrupole mass filter provided in the analysis chamber, but many ions having greatly different mass numbers are eliminated. be able to. In this way, the ions selected by the first multipole lens are introduced into the next intermediate vacuum chamber having a relatively low degree of vacuum at the next stage, and the collision with the residual gas molecules promotes the cleavage of the ions. Then, various ions generated by the cleavage are introduced into a mass analyzer such as a quadrupole mass filter, and separated and detected for each mass number.
[0010]
According to the experiment of the inventor of the present application, it is preferable that the pressure in the second intermediate vacuum chamber be 1 × 10 ⁻¹ Pa or more in order to effectively cause cleavage in the second intermediate vacuum chamber.
[0011]
【The invention's effect】
According to the atmospheric pressure ionization mass spectrometer according to the present invention, in an intermediate vacuum chamber provided in a plurality of stages between the ionization chamber and the analysis chamber, selection of ions having a specific mass number and cleavage of the selected ions. Is performed, and various ions including fragment ions are introduced into the mass analyzer. Therefore, analysis substantially similar to MS / MS can be performed, and the structure of a molecule or an atom can be easily estimated by analyzing the acquired mass spectrum. Further, since the configuration is simpler than that of a general MS / MS, the cost is relatively low, and the miniaturization like a desktop type can be achieved.
[0012]
Further, according to the atmospheric pressure ionization mass spectrometer according to the present invention, by appropriately changing the voltage applied to the first multipole lens, it is possible to perform only normal ion convergence without selecting ions. For example, a mass spectrum by collision-activated dissociation and a normal mass spectrum can be alternately acquired for each mass scan. In ordinary MS / MS, a reaction gas must be introduced into a collision reaction chamber to perform collision-activated dissociation analysis, and the reaction gas must be exhausted to perform ordinary analysis. Since it is impossible to perform such switching in a short time, the above-described analysis is impossible.
[0013]
【Example】
Hereinafter, an embodiment of the atmospheric pressure ionization mass spectrometer according to the present invention will be described with reference to the drawings. FIG. 1 is a schematic configuration diagram of an electrospray mass spectrometer (ESP-MS) according to the present embodiment.
[0014]
The MS comprises, for example, an ionization chamber 1 provided with a nozzle 2 connected to an outlet end of an LC column, and an analysis chamber 9 provided with a quadrupole mass filter 10 and an ion detector 11. A first intermediate vacuum chamber 4 and a second intermediate vacuum chamber 7 are provided, each separated by a partition. Between the ionization chamber 1 and the first intermediate vacuum chamber 4 is a small diameter desolvation pipe 3, and between the first intermediate vacuum chamber 4 and the second intermediate vacuum chamber 7 is a very small diameter passage hole (orifice). Only through a skimmer 6 having
[0015]
The inside of the ionization chamber 1 is almost at atmospheric pressure due to vaporized molecules of the sample solution continuously supplied from the nozzle 2. The inside of the first intermediate vacuum chamber 4 is evacuated to a low vacuum state of about 10 ² Pa by a rotary pump. Further, the inside of the second intermediate vacuum chamber 7 is evacuated to a medium vacuum state of about 10 ^-1 Pa by a turbo-molecular pump, and the inside of the analysis chamber 9 is raised to about 10 ^-3 to 10 ^-4 Pa by another turbo-molecular pump. It is evacuated to a vacuum. By increasing the degree of vacuum in each chamber from the ionization chamber 1 toward the analysis chamber 9 in this manner, the inside of the analysis chamber 9 is maintained in a high vacuum state.
[0016]
The schematic operation of this MS is as follows. The sample solution is sprayed (electrospray) from the nozzle 2 into the ionization chamber 1, and the sample molecules are ionized while the solvent in the droplets evaporates. Droplets containing ions are drawn into the desolvation pipe 3 by a pressure difference between the ionization chamber 1 and the first intermediate vacuum chamber 4, and further ionized in the process of passing through the desolvation pipe 3. In the first intermediate vacuum chamber 4, a quadrupole ion lens (first multipole lens) 5 is provided. The quadrupole ion lens 5 assists in attracting ions through the desolvation pipe 3 and also selects ions having a specific mass number and converges them near the orifice of the skimmer 6 as described later.
[0017]
The ions of a specific mass number introduced into the second intermediate vacuum chamber 7 through the orifice of the skimmer 6 are converged by a multipole lens (second multipole lens) 8 composed of a plurality of rod electrodes, and remain. Cleavage is accelerated by collision with molecular ions, and many fragment ions are generated and sent to the analysis chamber 9. Note that the multipole lens 8 may be composed of a plurality of flat electrodes. In the analysis room 9, only ions having a specific mass number among various ions pass through an axial space at the center of the quadrupole mass filter 10, reach the ion detector 11 and are detected.
[0018]
The first, second, and third voltage generators 12, 13, and 14 generate predetermined voltages to be applied to the quadrupole ion lens 5, the multipole lens 8, and the quadrupole mass filter 10, respectively. The voltage value is controlled by the control unit 15. Although not shown, a predetermined voltage (usually a DC voltage) is also applied to the nozzle 2, the desolvation pipe 3, the skimmer 6, and the like.
[0019]
Next, the configuration and operation of the quadrupole ion lens 5, which is one of the features of the present invention, will be described in detail. FIG. 2 is a detailed configuration diagram centering on the first intermediate vacuum chamber 4 and the second intermediate vacuum chamber 7 of the present MS, and FIG. 3 is a plan view of the quadrupole ion lens 5 viewed from the ion incident side.
[0020]
The quadrupole ion lens 5 includes four virtual rod electrodes 51 to 54 separated around the ion optical axis C, and the virtual rod electrodes 51 to 54 are separated from each other in the optical axis C direction. A large number (5 in this example) of circular metal plates are provided upright at predetermined intervals. The electrode plates 511 to 515, 521 to 525, 531 to 535, and 541 to 545 are arranged so as to be closer to the ion optical axis C as they proceed in the ion traveling direction, and the ion passing space surrounded by the electrode plates gradually increases. It has become narrow. Since the diameter of the electrode plate is determined based on a predetermined calculation formula depending on the distance from the ion optical axis C, the diameter becomes smaller as the ion travels. The envelope of each electrode plate group forms virtual rod electrodes 51-54.
[0021]
FIG. 2 shows only a pair of virtual rod electrodes 51 and 52 facing each other with the ion optical axis C interposed therebetween. The first voltage generator 12 includes a DC voltage generator and a high-frequency voltage generator, and receives a DC voltage X and a high-frequency voltage Y · cosθt (hereinafter referred to as a “high-frequency voltage Y”) in response to an instruction from the controller 15. "). The first voltage generator 12, the resistors R1 to R4, and the capacitors C1 to C5 apply a DC voltage to each of the electrode plates 521 to 525 in a stepwise manner as the voltage advances in the traveling direction of the ions (rightward in FIG. 2). And a common high frequency voltage Y are applied. As shown in FIG. 3, the same voltage (for example, voltage X + Y for the electrode plate 511) is applied to the electrode plates 511 to 515 facing the electrode plates 521 to 525 with the ion optical axis C interposed therebetween. A set of electrode plates 531 to 535 and 541 to 545 is supplied with a voltage having the same amplitude as that of the electrode plates existing in the same plane and having the polarity inverted (for example, voltage − (X + Y) for electrode plates 531 and 541). Each is applied.
[0022]
By such a voltage, a predetermined electric field similar to that in the space in the axial direction of the quadrupole mass filter 10 is formed in the ion passage space of the quadrupole ion lens 5. Therefore, the ions sucked into the first intermediate vacuum chamber 4 from the preceding ionization chamber 1 via the desolvation pipe 3 advance while vibrating at a predetermined cycle by the action of the electric field. Since the oscillation period varies depending on the applied voltage, by appropriately adjusting the voltage X (or both X and Y), ions having a specific mass number can be selectively converged to the rear focal position F. Since the orifice of the skimmer 6 is provided near the rear focal position F, only the ions converged near the rear focal position F pass through the orifice and are introduced into the second intermediate vacuum chamber 7, while the other ions are Exhausted without passing through the orifice. By narrowing the ion passage space in the traveling direction of the ions as in this embodiment, the convergence efficiency of the ions is increased, and more ions can be sent to the second intermediate vacuum chamber 7. .
[0023]
The second voltage generator 13 applies a voltage obtained by superimposing a high-frequency voltage and a DC voltage to the multipole lens 8. The DC voltage at this time is 30 to 200 V, which is higher than that in the case of performing normal (that is, not collision activated dissociation) analysis. Thereby, the ions are cleaved by collision with gas molecules remaining in the second intermediate vacuum chamber 7 to generate fragment ions. Since the mode of the cleavage at this time differs depending on the voltage value of the DC voltage applied to the multipole lens 8, it is preferable to appropriately adjust this voltage so that a desired cleavage occurs.
[0024]
The various ions including the fragment ions thus generated are introduced into the analysis chamber 9 by the differential pressure, and introduced into the space in the long axis direction of the quadrupole mass filter 10 as described above. As is conventionally known, the third voltage generator 14 applies a voltage ± (U + Vcosωt) obtained by superimposing a DC voltage having an inverted polarity and a high-frequency voltage to a rod electrode adjacent to the quadrupole.
[0025]
The control unit 15 controls the first voltage generation unit 12 so that the molecular ion of the target component is selected, and performs mass scanning so as to include the mass numbers of various fragment ions that may be generated by cleavage of the molecular ion. The third voltage generator 14 is controlled to perform the operation. By performing such control, a molecular ion of an undesired component other than the target component which is almost simultaneously ionized in the ionization chamber 1 is eliminated, so that a more accurate mass spectrum containing no unnecessary information is obtained. Can be.
[0026]
In the mass spectrometer according to the present embodiment, by changing the voltage applied to the quadrupole ion lens 5 and the multipole lens 8, the collision-activated dissociation analysis and the normal analysis as described above can be performed in a short time. You can switch. Therefore, by appropriately controlling the voltage, the collision-activated dissociation analysis and the normal analysis are alternately performed for each mass scan, or the mode of cleavage is changed even in the collision-activated dissociation analysis. Or different mass spectra can be obtained.
[0027]
The above embodiment is merely an example, and it is apparent that changes and modifications can be appropriately made within the scope of the present invention.
[Brief description of the drawings]
FIG. 1 is a schematic configuration diagram of an electrospray mass spectrometer according to one embodiment of the present invention.
FIG. 2 is a detailed configuration diagram centering on a first intermediate vacuum chamber and a second intermediate vacuum chamber in the mass spectrometer of the present embodiment.
FIG. 3 is a plan view of the quadrupole ion lens viewed from the ion incident side in the mass spectrometer of the present embodiment.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 ... Ionization chamber 2 ... Nozzle 3 ... Desolvation pipe 4 ... 1st intermediate vacuum chamber 5 ... Quadrupole ion lenses 51, 52, 53, 54 ... Virtual rod electrodes 511-515, 521-525, 531-535, 541-545 ... electrode plate 6 ... skimmer 7 ... second intermediate vacuum chamber 8 ... multipole lens 9 ... analysis room 10 ... quadrupole mass filter 11 ... ion detectors 12, 13, 14 ... voltage generator 15 ... controller

Claims (1)

A multistage differential pumping system comprising a plurality of intermediate vacuum chambers, each communicating through a small hole, between an ionization chamber at approximately atmospheric pressure and an analysis chamber at high vacuum and equipped with a mass spectrometer. Atmospheric pressure ionization mass spectrometer of
a) a first multipole lens disposed in a first intermediate vacuum chamber maintained in a low vacuum atmosphere next to the ionization chamber and including a virtual rod electrode;
b) the virtual rod electrode comprises an envelope of a plurality of electrode plates separated from each other in the ion optical axis direction;
c) the ion passage space surrounded by the electrode plate is configured to gradually narrow as it proceeds in the ion traveling direction;
d) With respect to the virtual rod electrode of the first multipole lens, a voltage obtained by superimposing a DC voltage and a high-frequency voltage, whose polarity is inverted between adjacent electrodes and has a voltage value corresponding to the mass number of the target ion. Voltage applying means for applying
e) disposed in a second intermediate vacuum chamber subsequent to the first intermediate vacuum chamber and maintained in a medium vacuum atmosphere, and applied with a voltage obtained by superimposing a high-frequency voltage and a DC voltage to promote cleavage of passing ions. A second multipole lens,
In addition, it is intended to select a target ion by a first multipole lens in a first intermediate vacuum chamber, promote cleavage of the target ion in a second intermediate vacuum chamber, and introduce various ions generated thereby into a mass spectrometer. Atmospheric pressure ionization mass spectrometer.

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