JPWO2020084738A1 - Mass spectrometer and program - Google Patents

Abstract

The mass spectrometer is a mass spectrometer including a triple quadrupole mass filter or a high-resolution mass spectrometer with a mass resolution of 5000 or more, and a mass spectrometer in which a plurality of columns are connected and samples supplied from the plurality of columns are mass-massed in parallel. It includes a connection unit that supplies the analysis unit and a control unit that controls the mass spectrometry unit.

Description

The present invention relates to mass spectrometers and programs.

As a mass spectrometer with excellent analysis accuracy, a gas chromatograph or liquid gas chromatograph is placed in the first stage, and a sample separated in time by the chromatograph is mass-analyzed by a mass spectrometer in the second stage. Is widely used.

In the chromatograph, it is necessary to replace the columns depending on the analysis target, but since it takes a relatively long time to replace the columns, a plurality of columns are arranged in parallel in order to avoid the equipment stoppage due to the column replacement. A mass spectrometer that can be installed has also been proposed (Patent Document 1).

Japanese Patent Application Laid-Open No. 2005-274474

Even if the conventional GC / MS and LC / MS mass spectrometers are provided with a plurality of columns, a plurality of samples are supplied in parallel from the plurality of columns, and the mass spectrometry is performed on the plurality of samples in parallel. It is not. Therefore, when analyzing a plurality of samples, it is necessary to analyze each sample separately in a time series, which causes a problem that a long analysis time is required.

According to the first aspect of the present invention, the mass spectrometer is connected to a mass spectrometer including a triple quadrupole mass filter or a high-resolution mass spectrometer having a mass resolution of 5000 or more, and a plurality of columns are connected to the plurality of columns. It includes a connection unit that supplies the sample supplied from the column to the mass spectrometry unit in parallel, and a control unit that controls the mass spectrometry unit.
According to the second aspect of the present invention, in the mass spectrometer of the first aspect, when the mass spectrometer includes the triple quadrupole mass filter, the control unit is supplied from the plurality of columns, respectively. Based on the components to be detected in the sample to be analyzed, the detection conditions for multiple reaction monitoring of the triple quadrupole mass filter are changed at predetermined time intervals.
According to the third aspect of the present invention, in the mass spectrometer of the second aspect, the control unit inputs the identification information for identifying the detection target component in the analysis target sample supplied from the plurality of columns, respectively. It has an input unit to be input, and the detection condition of multiple reaction monitoring is determined based on the identification information input from the input unit.
According to the fourth aspect of the present invention, in the mass spectrometer of the first aspect, the high resolution mass spectrometer is a time-of-flight mass spectrometer or a magnetic field mass spectrometer.
According to a fifth aspect of the present invention, in the mass spectrometer of any one of the first to fourth aspects, the control unit has a column oven that holds a plurality of columns connected to the connection unit, respectively. Controls the temperature of the column oven.
According to the sixth aspect of the present invention, in the mass spectrometer of the fifth aspect, columns having different holding characteristics are connected to the connecting portion.
According to the seventh aspect of the present invention, in the mass spectrometer of the sixth aspect, the column oven is configured to raise the temperature of the plurality of columns separately, and the control unit is the plurality of. The column oven is controlled so that the temperature of the column is controlled separately.
According to the eighth aspect of the present invention, in the mass spectrometer of any one of the first to fourth aspects, the output unit of the column of the different chromatographic apparatus is connected to the connection portion.
According to the ninth aspect of the present invention, in the control program for controlling the mass spectrometer, the control program causes a control device including a computer to control the temperature of a plurality of columns connected to the mass spectrometer, and the plurality of columns are controlled. The detection conditions for multiple reaction monitoring of the triple quadrupole mass filter are changed at predetermined time intervals based on the components to be detected in the sample to be analyzed supplied from each of the columns.

According to the present invention, it is possible to perform mass spectrometry on a plurality of samples supplied from a plurality of columns in parallel, thereby realizing a mass spectrometer that analyzes a plurality of samples in a short time.

FIG. 1 is a diagram showing a mass spectrometer of the first embodiment. FIG. 2 is a diagram showing a flowchart of mass spectrometry. FIG. 3 (a) is a diagram showing the retention time of each detection target component introduced into the column 12a, and FIG. 3 (b) is a diagram showing the retention time of each detection target component introduced into the column 12b, FIG. 3 (c). ) Is a diagram showing the relationship between the detection conditions D1 to D5 of multiple reaction monitoring and the elapsed time T. FIG. 4 is a diagram showing a mass spectrometer of the second embodiment.

(Mass spectrometer of the first embodiment)
FIG. 1 is a schematic view showing the configuration of the mass spectrometer 100 of the first embodiment. The mass spectrometer 100 is connected to the mass spectrometer 20, the chromatograph unit 10 having a plurality of columns 12a and 12b and surrounded by a broken line in FIG. 1, and the columns 12a and 12b, and the columns 12a and 12b are connected. It is provided with a connecting unit 15 that supplies the sample supplied from the above to the mass spectrometry unit 20 in parallel. The mass spectrometer 100 further includes a control unit 40 that controls the mass spectrometer 20 and the chromatograph unit 10.

As an example, the chromatograph unit 10 is a gas chromatograph.
In the first embodiment, the mass spectrometer 20 includes a so-called triple quadrupole mass filter, which includes a first quadrupole mass filter 24, a collision cell 26, and a second quadrupole mass filter 29.

The plurality of columns 12a and 12b are installed in the column ovens 13a and 13b, respectively, and sample injection portions 11a and 11b are provided on the sample introduction side of the columns 12a and 12b, respectively. Although not shown, carrier gas introduction sections for introducing carrier gas such as helium are provided on the sample introduction side of the columns 12a and 12b, and the samples injected into the sample injection sections 11a and 11b are It moves in the columns 12a and 12b together with the carrier gas. The output units (sample discharge side) 14a and 14b of the columns 12a and 12b are connected to the connection unit 15. As described above, the connecting unit 15 supplies the samples supplied from the columns 12a and 12b to the mass spectrometer 20 in parallel, that is, overlapping in time. The connecting portion 15 has, for example, the configuration disclosed in Patent Document 1 described above.

The sample supplied from the connection unit 15 is introduced into the ionization chamber 21 in the mass spectrometry unit 20. As an example, the ionization chamber 21 ionizes the molecules in the sample by an electron impact ionization method using electrons emitted from the filament 22. Molecules in the sample ionized in the ionization chamber 21 are guided to the first quadrupole mass filter 24 by the ion optical system 23.

A high frequency voltage (hereinafter referred to as "RF voltage") in which a predetermined DC voltage and an AC voltage having a predetermined voltage and frequency are mixed is applied to the first quadrupole mass filter 24 from the voltage supply unit 25. .. Similar to a normal quadrupole mass filter, by setting the RF voltage or voltage and frequency to the optimum values, only ions with a predetermined mass-to-charge ratio (m / z) (precursor ions) are selected. Therefore, the first quadrupole mass filter 24 can be transmitted.

The precursor ions that have passed through the first quadrupole mass filter 24 are incident on the collision cell 26.
A voltage obtained by mixing a predetermined DC voltage and an AC voltage having a predetermined voltage and frequency (hereinafter referred to as “collision voltage”) is also applied to the collision cell 26 from the voltage supply unit 27. Precursor ions are induced by this collision voltage and collide with an inert gas such as argon or nitrogen supplied into the collision cell 26. Due to the collision, the precursor ion is cleaved at the part where the chemical bond is weak, and a product ion is generated. The various product ions generated are guided by the ion optical system 28 and incident on the second quadrupole mass filter 29.

A predetermined RF voltage is applied to the second quadrupole mass filter 29 from the voltage supply unit 30. Due to this RF voltage, only product ions having a predetermined mass-to-charge ratio (m / z) pass through the second quadrupole mass filter 29 and are detected by the detector 31.
The components from the ionization chamber 21 to the detector 31 are arranged in the vacuum vessel 32 along the central axis AX of the ion optical systems 23, 28 and the like. The inside of the vacuum container 32 is exhausted by the vacuum pump 33.

As described above, the configuration from the first quadrupole mass filter 24 to the collision cell 26 and the second quadrupole mass filter 29 in the mass spectrometer 20 constitutes a triple quadrupole mass filter. .. Then, the triple quadrupole mass filter (24, 26, 29) can be used for detection by Multiple Reaction Monitoring (MRM).

In the multiple reaction monitoring, first, the first quadrupole mass filter 24 more selectively permeates only the ions having the same mass-to-charge ratio as the precursor ions derived from the component to be analyzed (component to be analyzed). After that, the ions that have passed through the first quadrupole mass filter 24 are cleaved in the collision cell 26 to generate product ions. Then, also in the second quadrupole mass filter 29, only ions having the same mass-to-charge ratio as the product ions derived from the component to be analyzed are more selectively permeated. Product ions that have passed through the second quadrupole mass filter 29 are detected by the detector 31.
In multiple reaction monitoring, the components to be analyzed are selected in two stages: selection of precursor ions by the first quadrupole mass filter 24 and selection of product ions by the second quadrupole mass filter 29. Can be done. Therefore, the component to be analyzed can be separated from other components with sufficient separation ability.

The control unit 40 controls the chromatograph unit 10 and the mass spectrometry unit 20, acquires data on the amount of detection detected by the detector 31, and analyzes and processes the acquired data.
The control unit 40 includes a CPU (Central Processing Unit) 41, which is a central processing unit, a memory 42, a hard disk (HD) 43, a display unit 44 including a liquid crystal panel, and an input unit 46 including a keyboard, a mouse, and the like. ..

The control unit 40 further includes an interface (I / F) 47 for controlling the direct connection with the external device and the connection with the external server 50 via the network cable NW. The CPU 41, the memory 42, the hard disk 43, and the interface 47 constitute a computer.
The memory 42 or the hard disk 43 stores a control program that controls the control unit 40, and also stores various information described later through the CPU 22. The memory 4 or the hard disk 43 contains identification information such as compound names, structural formulas, retention times for various columns, unique precursor ions and product ions, mass spectra, and the like as information necessary for analysis of various compounds. There is.
Instead of the hard disk 43, a solid state disk (SSD) composed of a semiconductor memory may be used.

FIG. 2 is a flowchart showing a flow of mass spectrometry by the mass spectrometer of the first embodiment. Each step in the flowchart shown in FIG. 2 is executed by controlling the control unit 40 by executing the control program by the CPU 41. In the description of each step below, the description of the control program and the CPU 41, which are the execution subjects, will be omitted.
The flowchart of FIG. 2 is based on the premise that the samples introduced into the columns 12a and 12b of the chromatograph unit 10 contain a total of N types of detection target components (N is an arbitrary natural number). The detection target component is a component to be detected (analyzed) by the mass spectrometer 100 from the sample.

In step S101, N loops are started with a natural number j equal to or less than N as a loop counter.
In step S102, the control unit 40 causes the display unit 44 to display a message prompting the input of the identification information Rj of the jth detection target component.
In step S103, the control unit 40 determines whether or not the identification information Rj has been input, and if not, returns to step S102.
If it is determined in step S103 that the identification information Rj has been input, the control unit 40 advances the control flow to step S104.

The identification information Rj includes identification information such as the name and abbreviation of the j-th detection target component, and information on which of the columns 12a and 12b is expected to be included in the sample supplied.
In step S104, the control unit 40 holds the j-th detection target component from the information on the holding times of the various compounds stored in the memory 42 or the hard disk 43 with respect to the columns 12a and 12b based on the identification information Rj. Read Tj. The holding time Tj includes a minimum holding time Tjs, which is the time when the derivation of the detection target component from the column 12a or the column 12b is started, and a maximum holding time Tje, which is the time when the derivation of the detection target component is completed. Street time shall be included.

In step S105, the control unit 40 reads out information on precursor ions and product ions specific to the compound corresponding to the identification information Rj from the memory 42 or the hard disk 43 based on the identification information Rj. Then, based on the information on the m / z of the peculiar precursor ion and the information on the m / z of the peculiar product ion, the j-th detection target component is detected in the multiple reaction monitoring (MRM) performed by the mass spectrometer 20. The optimum detection condition Dj is determined.

Specifically, based on the information on the m / z of the peculiar precursor ion, the condition of the RF voltage applied to the first quadrupole mass filter 24 in order to selectively permeate the peculiar precursor ion is determined. do. The collision voltage condition for efficiently inducing the above-mentioned peculiar precursor ion in the collision cell 26 to generate the above-mentioned peculiar product ion is determined. Further, based on the information regarding the m / z of the peculiar product ion, the condition of the RF voltage applied to the second quadrupole mass filter 29 in order to selectively transmit the peculiar product ion is determined.

When the holding time Tj corresponding to the identification information Rj and the information of the unique precursor ion and product ion are not in the memory 42 or the hard disk 43, the control unit 40 is transmitted from the external server 50 via the network cable NW. You may read those data.
In step S106, the above input and determination loop for the N analysis target components ends.

In step S107, the maximum value of the detection time (maximum detection time Tmax) is determined based on the retention time Tj (j is 1 to N) of the detection target component read above. Specifically, the maximum value in the above-mentioned maximum holding time Tje is adopted as the maximum detection time Tmax.
Then, the process proceeds to step S108, and the control unit 40 causes the display unit 44 to display a message urging the user to inject the sample to be analyzed into the sample injection units 11a and 11b.
In step S109, it is determined whether or not the user has injected the sample to be analyzed based on the input from the input unit 46, and if it has been injected, the process proceeds to step S110, and if it has not been injected, the process returns to step S108.

In step S109, the control unit 40 causes the kumatograph unit 10 and the mass spectrometry unit 20 to start the analysis of the sample. Specifically, the control unit 40 sends control signals S1a and S1b to the column ovens 13a and 13b of the kumatograph unit 10, respectively, to start the temperature rise. Then, the control unit 40 starts receiving the detection signal S5 from the detector 31. Then, the elapsed time T after the start of the analysis timed by the control unit 40 is reset to 0.

When the temperature rise of the column ovens 13a and 13b is started, the samples to be analyzed injected into the sample injection portions 11a and 11b move in the columns 12a and 12b at different speeds for each component and reach the connection portion 15. To reach. Then, the connecting unit 15 supplies the samples to be analyzed supplied from the columns 12a and 12b to the mass spectrometry unit 20 in parallel.

In step S111, N loops are started with a natural number j equal to or less than N as a loop counter.
In step S112, it is determined whether or not the above-mentioned elapsed time T corresponds to the holding time Tj of the j-th detection target component. That is, it is determined whether or not the elapsed time T is larger than the minimum holding time Tjs of the j-th detection target component and the elapsed time T is smaller than the maximum holding time Tje of the j-th detection target component.

If it is determined that the elapsed time T corresponds to the holding time Tj of the j-th detection target component, the process proceeds to step S113. Then, the control unit 40 sets the detection condition of the multiple reaction monitoring (MRM) to the mass spectrometric unit 20 to the optimum detection condition Dj for detecting the j-th detection target component described above. That is, the control unit 40 sends control signals S2 and S4 to the voltage supply units 25 and 30 of the mass spectrometry unit 20, respectively, and the voltage supply units 25 and 30 send the first quadrupole mass filter 24 and the second quadrupole mass filter. The 29 is supplied with the optimum RF voltage for the detection of the j-th detection target component. Further, the control unit 40 sends a control signal S3 to the voltage supply unit 27 of the mass spectrometry unit 20, and the voltage supply unit 27 sends the collision cell 26 the optimum collision voltage for inducing the peculiar precursor ion of the j-th detection target component. Supply.
After that, the process proceeds to step S114, and the detection signal S5 from the detector 31 is measured for a predetermined time (several msec to several hundred msec) under the detection condition Dj. Then, the process proceeds to step S115.

On the other hand, if it is determined in step S112 that the elapsed time T does not correspond to the holding time Tj of the j-th detection target component, the process proceeds to step S115.
In step S115, the loop started from step S111 ends.
Next, the process proceeds to step S116, and it is determined whether or not the elapsed time T exceeds the maximum detection time Tmax. Then, if the elapsed time T does not exceed the maximum detection time Tmax, the process returns to step S111 to continue the analysis. On the other hand, if the elapsed time T exceeds the maximum detection time Tmax, the analysis ends.

FIG. 3C shows an example of how the detection condition Dj of the multiple reaction monitoring (MRM) of the mass spectrometer 20 is set in the elapsed time T corresponding to the above steps S110 to S116. be.
3A and 3B are diagrams showing the holding time Tj (Tjs, Tje) (j is a natural number from 1 to N) read out by the control unit 40 corresponding to N detection target components. Is. Of these, FIG. 3A shows the retention times T1, T2, and T3 of the detection target components M1, M2, and M3 introduced into the column 12a, and FIG. 3B shows the detection target component M4 introduced into the column 12b. , M5 holding time T4, T5.
The scale of the horizontal axis (elapsed time) from FIG. 3 (a) to FIG. 3 (c) is the same.
In FIG. 3, the number N of the components to be detected is set to 5 as an example. Therefore, the value of j is also shown as 1 to 5.

In the example shown in FIG. 3, the retention time Tj of each detection target component has the smallest (shortest) retention time T1 of the first detection target component M1. After that, the retention time T4 of the fourth detection target component M4, the retention time T2 of the second detection target component M2, the retention time T5 of the fifth detection target component M5, and the third detection target component M3 in ascending order. The holding time is T3. Therefore, in the example of FIG. 3, the maximum holding time T3e of the third detection target component M3 is the maximum detection time Tmax determined in step S107. Further, the retention times T1 to T5 of each detection target component partially overlap each other.

When the elapsed time T is smaller than the minimum holding time T1s of the first detection target component M1, the determination in step S112 in the loop of j starting from step S111 is determined to be no. .. Therefore, at this time, steps S113 and S114 are not executed, the detection conditions for multiple reaction monitoring (MRM) are not set, and the measurement is not performed.

When the elapsed time T is larger than the minimum holding time T1s of the first detection target component M1 and smaller than the minimum holding time T4s of the fourth detection target component M4, the loop counter j of the loop starting from step S101 is 1. In this case, the determination in step S112 is Yes. Therefore, the process proceeds to step S113 and step S114, the optimum detection condition D1 for detecting the first detection target component M1 is set for the mass spectrometer 20, and the measurement is performed over a predetermined time.

When the elapsed time T is larger than the minimum holding time T4s of the fourth detection target component M4 and smaller than the maximum holding time T1e of the first detection target component M1, step S112 in the case of j = 1 and j = 4. The judgment in is Yes, and the process proceeds to step S113. Then, the optimum detection condition D1 for detecting the first detection target component M1 is set for the mass spectrometer 20 when j = 1, and the fourth detection target component M4 is set when j = 4. The optimum detection condition D4 for the detection of the above is set, and the measurement is performed over a predetermined time in step S114.

In this case, the detection target component M1 is introduced from the column 12a into the mass spectrometry unit 20, and the detection target component M4 is introduced from the column 12b in parallel via the connection unit 15. However, since the mass spectrometer 20 includes triple quadrupole mass filters (24, 26, 29), by operating these with multiple reaction monitoring (MRM), only specific detection target components M1 or M4 can be detected. Can be detected with high resolution. Therefore, even when different detection target components M1 and M4 are simultaneously introduced from the two columns 12a and 12b, the amounts of the respective detection target components M1 and M4 can be accurately analyzed.

On the other hand, if the mass spectrometer 20 does not include the triple quadrupole mass filter (24, 26, 29), it is not possible to detect only a specific analysis target component with high resolution. Therefore, in this case, when a plurality of detection target components having relatively close mass-to-charge ratios of precursor ions are simultaneously introduced from the two columns 12a and 12b, each detection target component is separated and accurately analyzed. I can't.

When the elapsed time T is larger than the maximum holding time T1e of the first detection target component M1 and smaller than the minimum holding time T2s of the second detection target component M2, the determination in step S112 is limited to the case of j = 4. Is Yes. Therefore, the process proceeds to step S113 and step S114, the optimum detection condition D4 for detecting the fourth detection target component M4 is set for the mass spectrometer 20, and the measurement is performed over a predetermined time.

Hereinafter, in the same manner, at each elapsed time T, the determination of step S112 is performed in the loop starting from step S111. Then, when the elapsed time T is included in the holding time Tj of the detection target component Mj, the process proceeds to step S113, and the control unit 40 detects the detection condition of the multiple reaction monitoring (MRM) with respect to the mass spectrometry unit 20. The optimum detection condition Dj is set for the target component Mj. Then, in step S114, the measurement is performed over a predetermined time.

In the example of FIG. 3, the number of the detection target components M1 to M5 in which the retention times Tj overlap in an arbitrary elapsed time is up to two, but three or more in an arbitrary elapsed time. The retention times Tj of the detection target components M1 to M5 may overlap. Even when three or more components to be detected are introduced at the same time, the amount of each component to be detected can be accurately analyzed by multiple reaction monitoring.

When used for the analysis of a plurality of the same detection target component Mj for each analysis, the input of the detection target component identification information Rj in steps S102 to S103 may be omitted in the flowchart of FIG. In that case, it is desirable to store the identification information and the like of each detection target component Mj in the hard disk 43 or the like in advance.

In the mass spectrometer 100 of the first embodiment described above, the columns 12a and 12b connected to the connecting portion 15 are not limited to the above two columns, and three or more columns may be connected. Further, in the above example, it is assumed that the column 12a and the column 12b are installed in different column ovens 13a and 13b, respectively, but the column 12a and the column 12b are installed in one common column oven. You may. Further, when the sample injection section has a connection section capable of connecting a plurality of columns, the column 12a and the column 12b may be connected to one common sample injection section.

When a plurality of columns 12a and 12b are installed in different column ovens 13a and 13b, respectively, the plurality of columns 12a and 12b are heated under different temperature rising conditions (temperature and temperature rising start time). Can be done. As a result, it is possible to separately control the arrival times of the components to be detected introduced from the plurality of columns 12a and 12b to the connecting portion 15 and the mass spectrometer 20, respectively, and avoid the overlap of the holding time Tj as much as possible. .. In this case, the retention time Mj of the detection target component Mj in the analysis-treated sample injected from the columns 12a and 12b shown in FIGS. 3 (a) and 3 (b) starts to increase in temperature. Make corrections over time.
On the other hand, when a plurality of columns 12a and 12b are installed in one common column oven, the column oven can be simplified and the cost of the apparatus can be reduced.

The columns 12a and 12b and the column ovens 13a and 13b are not indispensable, and a plurality of columns provided in the column oven prepared separately from the mass spectrometer 100 shall be connected to the connecting portion 15. You can also do it. In that case, the control unit 40 transmits control signals S1a and S1b to the separately prepared column oven to control the temperature rise of the column oven.

As an example, at least one of the plurality of columns provided in the separately prepared column oven may be a column provided in a chromatographic apparatus different from the mass spectrometer 100. In this case, the chromatograph unit 10 shown in FIG. 1 is a chromatograph device different from the mass spectrometer 100. Further, in this case, it is preferable that the control unit 40 transmits control signals S1a and S1b to the other chromatograph device to control the temperature rise of the column oven.

However, the control unit 40 does not necessarily have to control a column oven prepared separately or a column oven of another chromatograph device. For example, the control unit 40 receives a signal from a column oven prepared separately or a column oven of another chromatograph device to the effect that the temperature rise control has started, and the analysis start (elapsed time) in step S110 by this signal. (T reset) may be performed.

It is preferable that the plurality of columns 12a and 12b are columns having different holding characteristics (holding times for specific components are different).
If there are multiple columns with different retention characteristics, even if the sample to be analyzed to be injected into each column contains the same detection target component Mj, which one depends on the difference in retention time Tj with respect to the detection target component Mj of both columns. It is possible to separate whether or not the detection target component Mj is injected into the column of. Therefore, the amount of the detection target component Mj contained in the analysis target sample injected into each column can be accurately analyzed separately.

However, when the columns 12a and 12b are held in separate column ovens 13a and 13b whose temperature can be controlled individually as described above, the temperature rise start time is different between the columns 12a and 12b. Can be done. Therefore, even if a plurality of columns having the same retention characteristics are used, it is possible to make a difference in the time when the same detection target component Mj is introduced into the mass spectrometer 20 from both columns, and the detected detection target component Mj can be different. It is possible to separate from which column the is introduced.

The ionization chamber 21 included in the mass spectrometer 20 is not limited to the device adopting the above-mentioned electron collision method, and an device based on the chemical ionization method may be used.
Further, the chromatograph unit 10 is not limited to the gas chromatograph described above, and may be a liquid chromatograph. In this case, an ionization apparatus based on ESI (Electrospray ionization), atmospheric pressure chemical ionization (APCI), or atmospheric pressure photoionization source (APCI) may be used in the ionization chamber 21. preferable.

In the mass spectrometer 100 of the first embodiment described above, since a plurality of samples can be introduced in parallel from a plurality of columns 12a and 12b via the connecting portion 15 and analyzed in parallel. The analysis time when analyzing a plurality of samples can be significantly shortened.

(Mass spectrometer of the second embodiment)
FIG. 4 is a schematic view showing the configuration of the mass spectrometer 100a of the second embodiment. The mass spectrometer 100a of the second embodiment has the same configuration of the chromatograph unit 10 and the control unit 40 as the mass spectrometer 100 of the first embodiment described above. Therefore, the same reference numerals are given to the common parts, and the description thereof will be omitted as appropriate.
The mass spectrometer 100a of the second embodiment includes a mass spectrometer 20a surrounded by a broken line in FIG. 4, including a time-of-flight (TOF) high-resolution mass spectrometer 60. In the high-resolution mass spectrometer 60, an orthogonal acceleration electrode 62, a flight tube 63, and a detector 65 are arranged in the vacuum vessel 66. The inside of the vacuum container 66 is exhausted by the vacuum pump 67.

The sample-derived ions ionized in the ionization chamber 21 are guided by the ion optical system 61 and incident on the orthogonal acceleration electrode 62 in the high-resolution mass spectrometer 60. Then, it is pulsed downward in FIG. 4 by the orthogonal acceleration electrode 62, and flies along the flight path FP in the flight space FA in the flight tube 63. Then, it is reflected by the electric field formed by the reflector 64 and detected by the detector 65. The amount of ions detected by the detector 65 is transmitted to the control unit 40 as a detection signal S5a. Further, the pulsed acceleration of ions by the orthogonal acceleration electrode 62 is also controlled and executed by the control unit 40.

Since the velocities of the various ions accelerated downward by the orthogonal acceleration electrode 62 differ depending on the difference in the mass-to-charge ratio (m / z) of the ions, the flight time required for the flight of the same flight path FP is also the ions. It depends on the difference in mass-to-charge ratio. Therefore, by measuring the flight time, the mass-to-charge ratio of various ions can be measured.
In the time-of-flight high-resolution mass spectrometer 60, a high-resolution mass spectrometer with a mass resolution of 5000 or more capable of performing millimeter-mass measurement for examining the element composition by setting a long flight distance of ions in the flight tube 63. Can be realized. Further, in one flight of the sample (pulse acceleration by the orthogonal acceleration electrode 62), many kinds of ions having different m / z can be analyzed at the same time.

Also in the mass spectrometer 100a of the second embodiment, a plurality of columns 12a and 12b are connected to the mass spectrometer 20a via the connecting unit 15. Therefore, similarly to the first embodiment described above, there is a high possibility that a plurality of detection target components Mj are introduced into the mass spectrometry unit 20a from the columns 12a and 12b, respectively, with the holding times Tj overlapping.
In the mass spectrometer 100a of the second embodiment, the mass spectrometer 20a has a high-resolution mass spectrometer 60 having a mass resolution of 5000 or more. Therefore, even if a plurality of detection target components Mj are introduced from the plurality of columns 12a and 12b with overlapping time, the plurality of detection target components Mj are separated according to their respective mass-to-charge ratios (m / z). Can be detected separately. Thereby, each amount of each detection target component Mj can be accurately analyzed.

Therefore, also in the mass spectrometer 100a of the second embodiment, a plurality of samples can be introduced in parallel from the plurality of columns 12a and 12b via the connecting portion 15 and analyzed in parallel. The analysis time when analyzing a plurality of samples can be significantly shortened.

On the other hand, if the mass spectrometer 20a has a low resolution, if a plurality of detection target components Mj having relatively close mass-to-charge ratios when ionized are introduced in an overlapping manner in time, their respective detections will occur. The target component Mj cannot be separated and detected. Therefore, it is not possible to introduce a plurality of samples in parallel and perform analysis in parallel.

The high-resolution mass spectrometer 60 having a mass resolution of 5000 or more is not limited to the time-of-flight type described above, and a magnetic field type mass spectrometer such as a fan-shaped magnetic field type can also be used.

According to each of the above-described embodiments, the following effects can be obtained.
(1) The mass spectrometers 100 and 100a of each embodiment include mass spectrometers 20 and 20a including a triple quadrupole mass filter (24, 26, 29) or a high-resolution mass spectrometer 60 having a mass resolution of 5000 or more. A connection unit 15 in which a plurality of columns 12a and 12b are connected and samples supplied from the plurality of columns 12a and 12b are supplied in parallel to the mass spectrometers 20 and 20a, and a control unit that controls the mass spectrometers 20 and 20a. 40 and.
With this configuration, a plurality of samples introduced in parallel from a plurality of columns 12a and 12b via the connecting portion 15 can be analyzed in parallel, whereby a plurality of samples can be analyzed in parallel. The analysis time can be significantly reduced.

(2) When the mass spectrometer 20 includes a triple quadrupole mass filter (24, 26, 29), the control unit 40 controls the detection target component Mj in the analysis target sample supplied from the plurality of columns 12a and 12b, respectively. By changing the detection condition Dj of the multiple reaction monitoring of the triple quadrupole mass filter (24, 26, 29) at predetermined time intervals, the connection portion 15 can be connected from the plurality of columns 12a and 12b. A plurality of samples introduced at the same time via the route can be separated with higher accuracy for analysis.
(3) The control unit 40 has an input unit 46 into which identification information for identifying the detection target component Mj in the analysis target sample supplied from the plurality of columns 12a and 12b is input, and is input from the input unit 46. By configuring the detection condition Dj for multiple reaction monitoring based on the identification information, each of the various types of detection target components Mj can be detected and analyzed under the optimum detection condition Dj.

(4) In (1), the high-resolution mass spectrometer 60 can be used as a time-of-flight mass spectrometer or a magnetic field mass spectrometer, whereby a plurality of columns 12a and 12b can be used via the connection portion 15. A plurality of samples introduced in parallel can be separated with high accuracy for analysis.
(5) The column ovens 13a and 13b holding a plurality of columns 12a and 1b connected to the connection unit 15 respectively may be provided, and the control unit 40 may be configured to control the temperature of the column ovens 13a and 13b. .. As a result, the temperatures of the columns 12a and 1b can be controlled more accurately, and the holding time Tj of each detection sample can be controlled more accurately.

(6) By connecting columns 12a and 13a having different holding characteristics to each other, the same detection target component Mj is contained in the analysis target samples injected into the plurality of columns. Even so, the amount of the detection target component Mj contained in the analysis target sample injected into each column can be accurately analyzed separately.
(7) The column ovens 13a and 13b are configured to raise the temperature of the plurality of columns 12a and 12b separately, and the control unit 40 controls the temperature of the plurality of columns 12a and 12b separately. By controlling the columns 13a and 13b, not only the difference in the holding characteristics of the columns 12a and 12b but also the difference in the temperature rising conditions of the columns 12a and 12b are utilized to detect the component Mj from both columns 12a and 12b. Can be introduced into the mass spectrometer 20 at different times.
(8) The output units (14a, 14b) of the columns of different chromatographic apparatus may be connected to the connection unit 15. Thereby, the mass spectrometers 100 and 100a of the first embodiment or the second embodiment can be configured at low cost by utilizing the columns of the existing chromatographic apparatus.

(Program embodiment)
In the above-mentioned analysis using the mass spectrometer 100 in the above-mentioned first embodiment, the control program for realizing the above-mentioned function is recorded on a computer-readable recording medium, and the program recorded on the recording medium. May be loaded into the computer system and executed. As described above, when the program (control program) is executed by the CPU 41, the control unit 40 is controlled to execute each step in the flowchart shown in FIG.

The term "computer system" as used herein includes hardware of an OS (Operating System) and peripheral devices. The "computer-readable recording medium" refers to a portable recording medium such as a flexible disk, a magneto-optical disk, an optical disk, or a memory card, or a storage device such as a hard disk built in a computer system. Further, a "computer-readable recording medium" is a communication line for transmitting a program via a network such as the Internet or a communication line such as a telephone line, and dynamically holds the program for a short period of time. It may include a program that holds a program for a certain period of time, such as a volatile memory inside a computer system that serves as a server or a client in that case. Further, the above program may be for realizing a part of the functions of the above-mentioned control program, and further, the above-mentioned functions are realized by combining with a program already recorded in the computer system. You may.

Further, the above-mentioned program can be provided through a recording medium such as a CD-ROM or a data signal such as the Internet. For example, the control unit 40 including the CPU 41, the memory 42, and the hard disk HD32 in FIG. 1 receives a program from the optical drive DD45 via a CD-ROM. Further, the control unit 40 has a connection function with the network cable NW. The external server 50 connected to the network also functions as a server computer that provides the above program, and transfers the program to a recording medium such as a memory 42 and a hard disk HD32. That is, the program is carried as a data signal by a carrier wave and transmitted via the network cable NW. As described above, the program can be supplied as a computer-readable computer program product in various forms such as a recording medium and a carrier wave.
It should be noted that each step of the flowchart shown in FIG. 2 is not necessarily required to be executed at all.

(Effects of program embodiments)
(9) The program of the embodiment is a control program for controlling the mass spectrometer 100, wherein the control device (control unit) 40 including the computer (41, 42, 32) has a plurality of columns connected to the mass spectrometer 100. Multiple reaction monitoring of triple quadrupole mass filters (24, 26, 29) based on the detection target component Mj in the analysis target sample supplied from the plurality of columns 12a and 12b by controlling the temperature of 12a and 12b, respectively. The detection condition Dj of is changed at predetermined time intervals.
With this configuration, a plurality of samples introduced in parallel from a plurality of columns 12a and 12b can be analyzed in parallel, whereby the analysis time when analyzing a plurality of samples can be significantly shortened. Can be done.

The present invention is not limited to the contents of the above embodiment. Other aspects conceivable within the scope of the technical idea of the present invention are also included within the scope of the present invention.

100, 100a ... mass spectrometer, 10 ... chromatograph unit, 15 ... connection unit, 20, 20a ... mass spectrometer, 40 ... control unit (control device), 12a, 12b ... column, 13a, 13b ... column oven, 21 ... Ionization chamber, 23, 28 ... Ion optical system, 24 ... 1st quadrupole mass filter, 26 ... Collision cell, 29 ... 2nd quadrupole mass filter, 31, 65 ... Detector, 25, 27, 30 ... Voltage supply unit, M1 to M5 ... components to be detected, T1 to T5 ... holding time, D1 to D5 ... detection conditions, 16 ... orthogonal accelerator, 17 ... flight tube, 60 ... high resolution mass spectrometer (time-of-flight mass spectrometry) Total), 62 ... Orthogonal accelerator, 62 ... Flight tube

Claims (9)

A mass spectrometer including a triple quadrupole mass filter or a high resolution mass spectrometer with a mass resolution of 5000 or more,
A connection unit in which a plurality of columns are connected and samples supplied from the plurality of columns are supplied to the mass spectrometer in parallel, and a connection unit.
A control unit that controls the mass spectrometry unit and
A mass spectrometer. In the mass spectrometer according to claim 1,
When the mass spectrometer includes the triple quadrupole mass filter,
The control unit changes the detection conditions for multiple reaction monitoring of the triple quadrupole mass filter at predetermined time intervals based on the components to be detected in the sample to be analyzed supplied from the plurality of columns. Device. In the mass spectrometer according to claim 2,
The control unit
It has an input unit for inputting identification information for identifying the detection target component in the analysis target sample supplied from each of the plurality of columns.
A mass spectrometer that determines the detection conditions for multiple reaction monitoring based on the identification information input from the input unit. In the mass spectrometer according to claim 1,
The high-resolution mass spectrometer is a time-of-flight mass spectrometer or a magnetic field mass spectrometer, which is a mass spectrometer. In the mass spectrometer according to any one of claims 1 to 4.
It has a column oven that holds a plurality of columns connected to each of the connecting portions, and has a column oven.
The control unit is a mass spectrometer that controls the temperature of the column oven. In the mass spectrometer according to claim 5,
A mass spectrometer in which columns having different holding characteristics are connected to the connection portion. In the mass spectrometer according to claim 6,
The column oven is configured to heat the plurality of columns separately, and also
The control unit is a mass spectrometer that controls the column oven so as to control the temperature of the plurality of columns separately. In the mass spectrometer according to any one of claims 1 to 4.
A mass spectrometer in which a column output unit of a different chromatographic apparatus is connected to the connection portion. In the control program that controls the mass spectrometer
For control devices including computers
The temperature of a plurality of columns connected to the mass spectrometer is controlled, and the temperature is controlled.
Based on the components to be detected in the sample to be analyzed supplied from the plurality of columns, respectively.
A control program that changes the detection conditions for multiple reaction monitoring of a triple quadrupole mass filter at predetermined time intervals.

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