JP2008281469A - Mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a quadrupole type mass spectrometer capable of shortening time for a series of mass scanning and improving whole throughput by eliminating output stable time. <P>SOLUTION: This device comprises: an ionization chamber 11; lenses 15, 19 converging ion emitted from the ionization chamber 11; quadrupole type mass filters 22, 23 mass separating ion; a detector 24 detecting the ion which passed through quadrupole mass filters 22, 23; lens power source parts 31, 32 supplying voltage to the lenses 15, 19; a quadrupole power source part 33 supplying direct current voltage and high-frequency voltage to the quadrupole mass filters 22, 23; and a control part 6 controlling and mass scanning the lens power source parts 31, 32 and the quadrupole power source part 33. The control part 6 performs mass scanning of triangle wave which consists of linear increase from the minimum voltage corresponding to the minimum mass number to the maximum voltage corresponding to the maximum mass number and, following the linear increase, linear decrease from the maximum voltage to the minimum voltage which are alternately continuous. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a mass spectrometer used as a detector for liquid chromatograph mass spectrometry (LC / MS), and more particularly to a mass scanning (mass scanning) technique of a quadrupole mass spectrometer. .

  In a quadrupole mass spectrometer that uses a quadrupole mass filter as a mass separator, a quadrupole mass filter is applied by a voltage applied to four rod electrodes arranged parallel to each other so as to surround the central axis. pass. In other words, the mass number of ions to be selected is determined. Specifically, among the four rod electrodes, two rod electrodes facing each other across the central axis are + (U + V · cosωt), and the other two rod electrodes are − (U + V · cosωt). A voltage obtained by superimposing a high frequency voltage (V · cos ωt) on a direct current voltage (U) is applied. In this case, by changing the DC voltage value U and the amplitude value V of the high-frequency voltage, the mass number of ions that can pass through the space surrounded by the four rod electrodes changes (see Patent Document 1).

  That is, in the quadrupole mass spectrometer, only ions having a specific mass / number of charges (m / z) determined by the value of the DC voltage value U applied to the quadrupole mass filter and the amplitude value V of the high-frequency voltage are detected. Passing through the quadrupole mass filter with stable oscillation, other m / z ions diverge. Utilizing this phenomenon, the quadrupole mass filter is changed by changing both voltages while maintaining the DC voltage value U applied to the quadrupole mass filter and the amplitude value V of the high-frequency voltage in a predetermined relationship. The m / z of ions passing therethrough can be sequentially changed (mass scanning). By this mass scanning, various m / z ions contained in the sample are detected, and a mass chromatogram and a mass spectrum are obtained as a result of mass analysis based on the detected intensity of the ions. In mass spectrometry, even if the mass numbers are different, they cannot be distinguished if they have the same m / z. Therefore, in this specification, the mass number in the ordinary sense (the sum of the number of protons and the number of neutrons). ) A value obtained by dividing m by the number of charges z is called a “mass number”.

  In order to perform mass scanning over a predetermined mass range, U / V is generally kept constant, and U and V are changed with time. For example, when a mass spectrometer is used as a detector for a liquid chromatograph or a gas chromatograph, mass scanning over a predetermined mass range is repeated in order to detect various components in the sample obtained sequentially with time. Scan measurement is performed. Based on the detection signal obtained by the scan measurement, a mass spectrum having the mass number (mass-to-charge ratio m / z) on the horizontal axis and the ion intensity (signal intensity) on the vertical axis can be created.

  Up to now, at the time of mass scanning of the mass number m / z, for example, the minimum mass number MS = 10 m / z is set to the maximum mass number ME = 1000 m / z, and the sawtooth wave scanning is repeated.

In such a repetitive scan of the sawtooth waveform, scanning from the minimum mass number MS = 10 m / z to the maximum mass number ME = 1000 m / z and also starting from the minimum mass number MS = 10 m / z The setting of the voltage of the lens system, the DC voltage value U of the quadrupole mass filter, and the amplitude value V of the high-frequency voltage is set from the minimum voltage VMS corresponding to the minimum mass number _MS to the maximum mass number ME as shown in FIG. The maximum voltage _VME corresponding to the above is obtained, and the sawtooth waveform having the minimum voltage _VMS setting is repeatedly scanned. Varying from the maximum voltage V _ME to the minimum voltage V _MS, because it takes stable time of the output voltage, taking the output stabilization time T _S as shown in FIG. At present, an output stabilization time T _S = about 8 ms is required.
JP-A-10-27570

As described above, the repeated scanning of the sawtooth waveform in the conventional quadrupole mass spectrometer requires the output stabilization time T _S = 8 ms, the time required for a series of mass scanning is long, and the overall throughput is low. There was a problem.

The present invention has been made in order to solve the above-mentioned problems, and its object is to eliminate the output stabilization time T _S , to shorten the time required for a series of mass scans, and to improve the overall throughput. An object of the present invention is to provide a mass spectrometer capable of

In order to achieve the above object, an embodiment of the present invention includes (a) an ionization chamber for ionizing a sample;
(B) a lens that converges ions emitted from the ionization chamber, (c) a quadrupole mass filter that mass-separates ions, (d) a detector that detects ions that have passed through the quadrupole mass filter, E) a lens power supply for supplying voltage to the lens, (f) a quadrupole power supply for supplying DC voltage and high frequency voltage to the quadrupole mass filter, and (g) a lens power supply and a quadrupole power supply. The gist of the present invention is that the mass spectrometer includes a control unit that controls mass and scans the mass. The control unit of the mass spectrometer according to the aspect of the present invention includes a linear increase from the minimum voltage corresponding to the minimum mass number to the maximum voltage corresponding to the maximum mass number, and the maximum voltage to the minimum voltage following the linear increase. It is characterized by performing mass scanning of a triangular wave consisting of repetition of linear reduction up to.

According to the present invention, it is possible to provide a mass spectrometer that can eliminate the output stabilization time T _S , reduce the time required for a series of mass scans, and improve the overall throughput.

  Next, embodiments of the present invention will be described with reference to the drawings. In the following description of the drawings, the same or similar parts are denoted by the same or similar reference numerals. Further, the embodiments described below exemplify apparatuses and methods for embodying the technical idea of the present invention. The technical idea of the present invention includes components, circuit, and the like described below. It is not something specific. The technical idea of the present invention can be variously modified within the technical scope described in the claims.

  As shown in FIG. 1, the quadrupole mass spectrometer according to the embodiment of the present invention includes an ionization chamber 11 that is an ion source, a pre-quadrupole mass filter 22, a main quadrupole mass filter 23, and It is a liquid chromatogram mass spectrometer (LC / MS) provided with the analysis chamber 21 in which the detector 24 is disposed. This liquid chromatogram mass spectrometer uses an electrospray ionization method, which is one of atmospheric pressure ionization methods, as an ionization section, and is connected to the column outlet end of a liquid chromatograph (not shown) in the ionization chamber 11. A nozzle 12 is provided. A first intermediate vacuum chamber 14 and a second intermediate vacuum chamber 18 are provided between the ionization chamber 11 and the analysis chamber 21, respectively, separated by a partition wall. Further, the ionization chamber 11 and the first intermediate vacuum chamber 14 communicate with each other via a thin solvent removal pipe 13, and the skimmer 16 is connected between the first intermediate vacuum chamber 14 and the second intermediate vacuum chamber 18. It passes through a through hole (orifice) 17 having a very small diameter provided at the top. The second intermediate vacuum chamber 18 and the analysis chamber 21 communicate with each other through a small opening provided in the partition wall 20.

The inside of the ionization chamber 11 is in an atmospheric pressure atmosphere (about 100 kPa) due to vaporized molecules of the liquid sample continuously supplied from the nozzle 12, and the inside of the first intermediate vacuum chamber 14 in the next stage is a rotary pump 27. Is evacuated to a low vacuum state of about 10 ² Pa. Further, the inside of the second intermediate vacuum chamber 18 at the next stage is evacuated to a medium vacuum state by about 10 ⁻¹ to 10 ⁻² Pa by a turbo molecular pump 28, and another turbo molecule is inside the analysis chamber 21 at the final stage. The pump 29 is evacuated to a high vacuum state of about 10 ⁻³ to 10 ⁻⁴ Pa. In other words, a multi-stage differential exhaust system in which the degree of vacuum is increased stepwise from the ionization chamber 11 to the analysis chamber 21 to maintain the inside of the final analysis chamber 21 in a high vacuum state. ing.

  Although the structures of the first intermediate vacuum chamber 14 and the second intermediate vacuum chamber 18 are different from each other, an ion optical system is provided for efficiently transporting ions to the subsequent stage. That is, a first lens electrode 15 is provided in the first intermediate vacuum chamber 14 in which a plurality of (four) plate-like electrodes are arranged in three rows in an inclined manner, and is removed by an electric field formed by the electrodes 15. While helping to draw ions through the solvent pipe 13, the ions are converged near the orifice 17 of the skimmer 16. The second intermediate vacuum chamber 18 is provided with an octapole-type second lens electrode 19 in which eight rod electrodes are arranged so as to surround the ion optical axis C, whereby ions are converged and analyzed. It is sent into the chamber 21.

  The first lens electrode 15, the second lens electrode 19, the pre-quadrupole mass filter 22, and the main quadrupole mass filter 23 have a first lens power supply unit 31, a second lens power supply unit 32, and a quadrupole power supply unit 33, respectively. A predetermined voltage is applied. In particular, the pre-quadrupole mass filter 22 and the main quadrupole mass filter 23 have a predetermined high-frequency voltage Vcosωt generated by the RF generation unit 36 and a predetermined generation generated by the DC generation unit 34 according to the mass number to be selected. The voltage ± (U + V · cos ωt) obtained by adding the DC voltage U of the current and the direct current voltage U to the combining unit 35 is applied.

The operations of the first lens power supply unit 31, the second lens power supply unit 32, the quadrupole power supply unit 33, and the like are comprehensively controlled by a control unit 6 mainly composed of a microcomputer. In addition to the one shown in FIG. 1, a predetermined voltage (mainly DC voltage) is applied to each part, but the description is omitted because the drawing becomes complicated. The control unit 6 has a function of setting the voltage of the first lens power supply unit 31, the voltage of the second lens power supply unit 32, the DC voltage value U of the quadrupole power supply unit 33, and the amplitude value V of the high-frequency voltage during mass scanning. . That is, the control unit 6 sets the voltage of the first lens power supply unit 31, the voltage of the second lens power supply unit 32, the DC voltage value U of the quadrupole power supply unit 33, and the amplitude value V of the high frequency voltage in FIG. As shown, the voltage output stabilization time T _S is eliminated by setting a triangular wave shape that linearly increases from the minimum voltage V _MS to the maximum voltage V _ME and then decreases linearly from the maximum voltage V _ME to the minimum voltage V _MS. , Reduce the time taken for a series of mass scans and improve throughput. Minimum voltage V _MS corresponds to the minimum mass number MS, the maximum voltage V _ME corresponds to the maximum mass number ME. The minimum mass number MS is, for example, 10 m / z, and the maximum mass number ME is, for example, 1000 m / z. A time T1 for scanning the maximum voltage V _ME from the minimum voltage V _MS, the time T2 for scanning the minimum voltage V _MS from the maximum voltage V _ME, but not necessarily equal, of course it may be T1 = T2 is there. The voltage of the first lens power supply unit 31, the voltage of the second lens power supply unit 32, the DC voltage value U of the quadrupole power supply unit 33 and the amplitude value V of the high frequency voltage are set in a triangular waveform as shown in FIG. By doing so, the output stabilization time T _S can be eliminated, so that the time required for a series of mass scans can be reduced and the throughput can be improved.

  As shown in FIG. 2, the control unit 6 includes a programmable logic device (PLD) such as a field programmable gate array (FPGA) 61, an arithmetic processing circuit such as a central processing unit (CPU) 62, and the like. A storage device such as a mass scanning setting table 63 is provided.

In the mass scan setting table 63, ions having respective mass numbers in the mass range between the minimum mass number MS and the maximum mass number ME that can be measured by the quadrupole mass spectrometer according to the embodiment are pre-quadruplexed. Mass scanning reference data for determining a voltage that is a condition for passing through the pole mass filter 22 and the main quadrupole mass filter 23 is stored corresponding to each mass number m / z. That is, in the mass scan setting table 63, the settings of the voltage of the first lens power supply unit 31, the voltage of the second lens power supply unit 32, the DC voltage value U of the quadrupole power supply unit 33 and the amplitude value V of the high frequency voltage are set. As shown in FIG. 3, parameters of mass scanning set in a triangular wave shape that linearly increases from the minimum voltage V _MS to the maximum voltage V _ME and linearly decreases from the maximum voltage V _ME to the minimum voltage V _MS are stored. .

  As shown in FIG. 2, the CPU 62 includes a scan control module 621, a parameter setting module 622, a signal A / D control module 623, and the like.

  As shown in FIG. 2, the FPGA 61 includes a scan D / A setting module 611, a signal A / D processing module 612, and the like. Connected to the FPGA 61 are a first lens D / A converter 64, a second lens D / A converter 65, a quadrupole DC D / A converter 66, a quadrupole RF D / A converter 67, and a signal A / D converter 68. Has been. The first lens D / A converter 64, the second lens D / A converter 65, the quadrupole DC D / A converter 66, the quadrupole RF D / A converter 67, and the signal A / D converter 68 are respectively The 1 lens power supply unit 31, the second lens power supply unit 32, the DC generation unit 34 of the quadrupole power supply unit 33, the RF generation unit 36 of the quadrupole power supply unit 33, and the detector 24 are connected.

  The first lens D / A converter 64 converts the data sent from the scan D / A setting module 611 of the FPGA 61 into an analog voltage and outputs it to drive the first lens power supply unit 31 to generate a DC voltage value. The second lens D / A converter 65 converts the data sent from the scan D / A setting module 611 into an analog voltage and outputs it, and drives the second lens power supply unit 32 to generate a DC voltage value. The quadrupole DC D / A converter 66 converts the data sent from the scan D / A setting module 611 into an analog voltage and outputs it, and drives the DC generator 34 of the quadrupole power supply unit 33 to drive the DC voltage value U. Is generated. The quadrupole RF D / A converter 67 converts the data sent from the scan D / A setting module 611 into an analog voltage and outputs it, and drives the RF generation unit 36 of the quadrupole power supply unit 33 to drive the amplitude of the high frequency voltage. Generate the value V. The signal A / D converter 68 converts the analog data sent from the detector 24 into digital data, outputs it, and sends it to the signal A / D processing module 61 of the FPGA 61.

As a result, the control unit 6 sets the voltage of the first lens power supply unit 31, the voltage of the second lens power supply unit 32, the DC voltage value U of the quadrupole power supply unit 33 and the amplitude value V of the high frequency voltage as shown in FIG. as shown in, the maximum voltage V _ME from the minimum voltage V _MS, and, by setting the maximum voltage V _ME to the minimum voltage V _MS in triangular waveform, eliminating the output stabilization time T _S of the voltage, a series of mass scan It is possible to improve the throughput by shortening the time required for.

  Next, the operation of the quadrupole mass spectrometer according to the embodiment of the present invention will be schematically described. The liquid sample supplied almost continuously is sprayed (electrospray) into the ionization chamber 11 while being charged from the tip of the nozzle 12, and the sample molecules are ionized in the process of evaporating the solvent in the droplets. Fine droplets mixed with ions are drawn into the desolvation pipe 13 due to the differential pressure between the ionization chamber 11 and the first intermediate vacuum chamber 14, and further the solvent is vaporized in the process of passing through the heated desolvation pipe 13. Is promoted and ionization proceeds. With the help of the electric field formed by the first lens electrode 15 disposed in the first intermediate vacuum chamber 14, the ions enter the first intermediate vacuum chamber 14, are converged and pass through the orifice 17 to form the second intermediate vacuum chamber. 18 is sent.

  In the second intermediate vacuum chamber 18, ions are further converged and sent to the analysis chamber 21 by the action of the electric field formed by the octopole-type second lens electrode 19. In the analysis chamber 21, only ions having a specific mass number determined by the voltage applied to each rod electrode pass through the space in the long axis direction of the pre-quadrupole mass filter 22 and the main quadrupole mass filter 23. Ions with other mass numbers diverge on the way. The ions that have passed through the pre-quadrupole mass filter 22 and the main quadrupole mass filter 23 reach the detector 24, and the detector 24 outputs an ion intensity signal corresponding to the amount of ions. The detection signal from the detector 24 is converted into digital data and input to a data processing device in the control unit 6 where predetermined data processing is executed.

In the quadrupole mass spectrometer according to the embodiment of the present invention, the voltage ± (U + V · cosωt) applied to the pre-quadrupole mass filter 22 and the main quadrupole mass filter 23 from the quadrupole power supply unit 33. Mass scanning can be performed by scanning the DC voltage value U and the amplitude value V of the high-frequency voltage while keeping the U / V relationship constant. At that time, since the scanning of the DC voltage value U is controlled to be a triangular wave as shown in FIG. 3, the voltage output stabilization time T _S is eliminated, the time required for a series of mass scanning is shortened, and the throughput Can be improved.

  Although the present invention has been described with reference to the above-described embodiments, it should not be understood that the description and drawings constituting a part of this disclosure limit the present invention. From this disclosure, various alternative embodiments, examples and operational techniques will be apparent to those skilled in the art.

  The above description of the embodiment is merely an example, and it is apparent that changes and modifications can be made as appropriate within the scope of the present invention. For example, the configuration of the control unit 6 is merely an example, and the same function can be achieved even if it is appropriately changed.

  As described above, the present invention naturally includes various embodiments not described herein. Therefore, the technical scope of the present invention is defined only by the invention specifying matters according to the scope of claims reasonable from the above description.

1 is an overall configuration diagram of a quadrupole mass spectrometer according to an embodiment of the present invention. It is a block block diagram explaining the outline of the principal part of the control part of the quadrupole mass spectrometer shown in FIG. It is a figure for demonstrating the mass scan of the quadrupole-type mass spectrometer which concerns on embodiment of this invention. It is a figure for demonstrating the mass scan of the conventional quadrupole-type mass spectrometer.

Explanation of symbols

DESCRIPTION OF SYMBOLS 11 ... Ionization chamber 12 ... Nozzle 13 ... Desolvation pipe 14 ... 1st intermediate | middle vacuum chamber 15 ... 1st lens electrode 15 ... Electrode 16 ... Skimmer 17 ... Orifice 18 ... 2nd intermediate | middle vacuum chamber 19 ... 2nd lens electrode 20 ... Partition DESCRIPTION OF SYMBOLS 21 ... Analysis chamber 22 ... Pre quadrupole mass filter 23 ... Main quadrupole mass filter 24 ... Detector 27 ... Rotary pump 28 ... Turbo molecular pump 29 ... Turbo molecular pump 31 ... 1st lens power supply part 32 ... 2nd lens Power supply unit 33 ... quadrupole power supply unit 34 ... DC generation unit 35 ... synthesis unit 36 ... RF generation unit 61 ... processing module 61 ... FPGA
62 ... CPU
63 ... Mass scan setting table 64 ... First lens D / A converter 65 ... Second lens D / A converter 66 ... Quadrupole DC D / A converter 67 ... Quadrupole RF D / A converter 68 ... Signal A / D Converter 611 ... Scan D / A setting module 612 ... Signal A / D processing module 621 ... Scan control module 622 ... Parameter setting module 623 ... Signal A / D control module

Claims (1)

An ionization chamber for ionizing the sample;
A lens that focuses ions emitted from the ionization chamber;
A quadrupole mass filter for mass separating the ions;
A detector that detects the ions that have passed through the quadrupole mass filter;
A lens power supply for supplying a voltage to the lens;
A quadrupole power supply for supplying a DC voltage and a high frequency voltage to the quadrupole mass filter;
A control unit configured to control the lens power supply unit and the quadrupole power supply unit to perform mass scanning, and the control unit is configured to perform linear operation from a minimum voltage corresponding to the minimum mass number to a maximum voltage corresponding to the maximum mass number. A mass spectrometer which performs mass scanning of a triangular wave consisting of an increase and a repetition of a linear decrease from the maximum voltage to the minimum voltage following the linear increase.

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