Method for controlling mass spectrometer, mass spectrometer

Abstract

The purpose of the present disclosure is to provide a method that is for controlling a mass spectrometer and that enables inhibition of a decrease in sensitivity in a high ion concentration region without changing a dwell time for each data point. In the method for controlling a mass spectrometer according to the present disclosure, collection of data is started at the same regular time interval, and the length of time during which the data is collected varies depending on the level of space charge generated in a pre-filter or the level of sensitivity deterioration in the mass spectrometer decreases caused by the space charge (see fig. 4B).

Description

[Technical Field]

[0001] The present disclosure relates to a method for controlling a mass spectrometer. [Background technology]

[0002] A multipole mass spectrometer includes an ion source that ionizes compounds in a sample, a mass separator such as a multipole mass filter that separates ions derived from the compounds according to their mass-to-charge ratio (m / z), and a detector that detects the separated ions. A prefilter is placed before the multipole mass filter to remove, for example, non-target ions.

[0003] When a large amount of ions are input to a mass spectrometer, a space charge (ion accumulation, also called spatial charge) occurs near the prefilter, which can reduce the sensitivity of the mass spectrometer. As a countermeasure to this, a technique for changing the dwell time according to the amount of ions is known (Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 09-306419 Summary of the Invention [Problem to be solved by the invention]

[0005] In Patent Document 1, the dwell time varies depending on the amount of ions. The dwell time here refers to the sampling interval when sampling data points from a chromatogram (data describing the amount of ions measured by a mass spectrometer). If the sampling interval varies for each data point, as in Patent Document 1, there is a problem in that the data analysis procedure becomes complicated.

[0006] The present disclosure has been made in consideration of the above-mentioned problems, and aims to provide a method for controlling a mass spectrometer that can suppress a decrease in sensitivity in high ion concentration regions without changing the dwell time for each data point. [Means for solving the problem]

[0007] A method for controlling a mass spectrometer according to the present disclosure starts collecting data at the same time intervals, and the length of time for collecting the data varies depending on the degree of space charge generated in a prefilter or the degree of reduction in sensitivity of the mass spectrometer due to the space charge. [Effects of the Invention]

[0008] According to the method for controlling a mass spectrometer according to the present disclosure, it is possible to suppress a decrease in sensitivity in a high ion concentration region without changing the dwell time for each data point. [Brief explanation of the drawings]

[0009] [Figure 1] 1 is a diagram illustrating the overall configuration of a mass spectrometer 100 according to a first embodiment. [Figure 2] 1 is a schematic diagram showing space charges in a mass spectrometer 100. FIG. [Figure 3] 10 is a graph showing a decrease in sensitivity of the ion detector 109 due to space charging. [Figure 4A] FIG. 1 is a schematic diagram showing a peak on a chromatogram, data points on the peak, and the relationship of dwell times between adjacent data points. [Figure 4B] FIG. 2 is a diagram illustrating data sampling in the first embodiment. [Figure 5A] FIG. 1 is a schematic diagram illustrating a time frame in conventional data sampling. [Figure 5B] FIG. 2 is a schematic diagram showing a time frame of data sampling in the first embodiment. [Figure 6]1 is a flowchart illustrating a procedure for measuring the amount of ions by the mass spectrometer 100. [Figure 7] 10 is an example of time length data describing a rule for calculating a data collection time length (Ti). [Figure 8] 10 is a flowchart illustrating a procedure for measuring the amount of ions by the mass spectrometer 100 in the second embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0010] <First Embodiment> 1 is a diagram showing the overall configuration of a mass spectrometer 100 according to a first embodiment of the present disclosure. The mass spectrometer 100 includes a measurement unit 101, an analog-to-digital converter (ADC) 102, a data analysis unit 103, and an analysis control unit 104 (controller). The measurement unit 101 further includes an ion introduction unit 105 and a vacuum chamber unit 106. The ion introduction unit 105 includes a sample introduction tube 105a and a gas introduction unit 105b. The vacuum chamber unit 106 includes electrodes 107a to 107d, a multipole ion guide 108a, a pre-filter 108b, a multipole mass filter 108c, a multipole post-filter 108d, and an ion detection unit 109.

[0011] The analog-to-digital converter 102 converts the ion quantity signal output by the ion detector 109 into digital data. The data analyzer 103 uses the digital data to analyze the ion quantity. The analysis controller 104 controls the overall operation of the mass spectrometer 100, including controlling the polarity of each electrode.

[0012] 2 is a schematic diagram showing the space charge in the mass spectrometer 100. When the amount of ions to be analyzed input into the mass spectrometer 100 is large (for example, 1.0×10 7When the ion density (cps) is equal to or greater than 100 s / s, a space charge occurs in the pre-filter 108b. When a space charge occurs, the electric field in the pre-filter 108b changes, and the amount of ions passing through decreases. cps stands for counts per second, i.e., the number of ions counted per second. The counts represent the signal intensity of ions detected by the ion detector 109 within the integration time.

[0013] 3 is a graph showing the decrease in sensitivity of the ion detection unit 109 due to space charge. Even if the time length of the process for measuring the amount of ions is as short as several tens of milliseconds, the decrease in sensitivity due to space charge may occur during the measurement time. The decrease in sensitivity at the start of the graph in FIG. 3 shows this.

[0014] FIG. 4A is a schematic diagram showing the relationship between peaks on a chromatogram, data points on the peaks, and the dwell time between adjacent data points. This diagram shows an example of dwell time in the prior art. The dwell time (Td) in a measurement (multiple reaction monitoring mode or selected ion monitoring mode) is the time it takes for the ion detection unit 109 to acquire signal intensity data during a given transition, and corresponds to the sampling interval. A wait time (Tw) of a certain length is placed after the dwell time. During the wait time, processing other than data collection is performed, such as discharging ions accumulated in the prefilter 108b.

[0015] The data analysis unit 103 collects ion amount data (i.e., acquires an ion amount signal) within the range of the dwell time from the ion detection unit 109. In the prior art, the dwell time (Td) and the data collection time (Ti) have the same time length.

[0016] In conventional technology, to prevent sensitivity degradation due to space charge, the dwell time (Td) is changed for each sampling timing depending on the ion amount. Accordingly, the data collection time (Ti) also changes for each sampling timing. When the dwell time (Td) is changed, the number of data points differs for each measurement, and therefore the analysis procedure differs for each measurement. This poses the problem of complicating the analysis procedure. For example, it may become necessary to implement analysis processes such as curve fitting for each number of data points.

[0017] FIG. 4B is a diagram illustrating data sampling in the first embodiment. In the first embodiment, the dwell time length (Td) is constant and does not change for each sampling time. When the ion amount is large, data collection is terminated before sensitivity decreases due to space charge. That is, the data collection time length (Ti) within the dwell time is changed according to the ion amount. As a result, Ti≦Td in the first embodiment.

[0018] In this first embodiment, the dwell time (Td) is fixed, so analysis can be performed using the same data analysis procedure at any sampling timing. By changing the data collection time (Ti) while keeping the dwell time (Td) fixed, it is possible to standardize the number of data points for each measurement. By standardizing the number of data points, data analysis procedures such as curve fitting can be fixed, reducing the burden of data analysis.

[0019] 5A is a schematic diagram showing a time frame in conventional data sampling, in which the dwell time (Td) and data collection time (Ti) vary for each sampling cycle.

[0020] 5B is a schematic diagram showing the time frame of data sampling in the first embodiment. Since the dwell time length (Td) is fixed, if the data collection time length (Ti) is shortened depending on the amount of ions, an excess time (residual time Tr; several milliseconds to several tens of milliseconds) will be generated within the dwell time. The residual time (Tr) is automatically determined by subtracting the data collection time length (Ti) from the dwell time (Td) set at the start of measurement, as shown in the following formula (1):

[0021] Tr=Td-Ti...Formula (1)

[0022] 6 is a flowchart illustrating the procedure for measuring the amount of ions by the mass spectrometer 100. This flowchart is executed by the analysis control unit 104. Each step in FIG. 6 will be described below.

[0023] (Figure 6: Step S201) The user sets the maximum number nmax (a natural number) of sampling cycles for acquiring ion quantity signals and the length of the dwell time (Td). The analysis control unit 104 stores the settings in a storage device.

[0024] (Figure 6: Step S202) The analysis control unit 104 performs a pre-scan to calculate the data collection time length (Ti) of the first sampling cycle (cycle 1). The pre-scan is a scan to obtain the ion amount before performing cycle 1. In other words, in this flowchart, the data collection time length (Ti) is calculated according to the ion amount described in the previously acquired ion amount data.

[0025] (Figure 6: Step S203) The analysis control unit 104 calculates the data acquisition time length (Ti) according to the ion amount described in the ion amount data acquired by the pre-scan. The calculation rules will be explained again later with reference to FIG.

[0026] (Figure 6: Step S204) The analysis control unit 104 repeats the following steps S205 to S208 until the maximum number of cycles nmax is reached. The cycle number is represented by the variable n.

[0027] (Figure 6: Steps S205 to S206) The analysis control unit 104 collects ion amount data for cycle n over the data collection time length (Ti) in that cycle (S205). After the data collection time has elapsed, the remaining time (Tr) elapses (S206).

[0028] (Figure 6: Step S207) The analysis control unit 104 reverses the polarity of the pre-filter voltage during the wait time (Tw) to eject ions accumulated in the pre-filter 108b. This ion ejection operation allows data collection to begin in a state where the space charge has been eliminated at the start of each dwell time.

[0029] (Figure 6: Step S208) The analysis control unit 104 calculates the data acquisition time length (Ti) required to ensure data acquisition accuracy for the (n+1)th data acquisition In+1, based on the ion amount described in the ion amount data obtained as a result of the nth data acquisition In. The calculation rules will be explained again later with reference to FIG. 7.

[0030] (Figure 6: Steps S203 and S208: Supplementary information) A preset initial value may be used as the initial value of the data acquisition time length Ti of data acquisition I1 in cycle 1, instead of calculating it based on the results of the pre-scan. The preset initial value may be selected by the user from the results of measuring the ion amount in advance, or may be input directly.

[0031] FIG. 7 is an example of time length data describing a rule for calculating the data collection time length (Ti). In this example, when the ion amount is X (cps) or less, the data collection time length (Ti) is the same as the dwell time (Td) (Ti = Td). When the ion amount is X (cps) or more, the data collection time length (Ti) becomes shorter as the ion amount increases (Ti < Td). The threshold value X (cps) may be made changeable by the user, for example, using experimental results.

[0032] In the example of FIG. 7, the data collection time length was made constant from an ion amount of 0 to X. Instead, the data collection time length may be made to monotonically decrease as the ion amount increases as long as the ion amount is 0 or more. Furthermore, the relationship between the data collection time length and the ion amount is not limited to a linear function, and any function may be used as long as the data collection time length decreases as the ion amount increases. In other words, the data collection time length Ti may be determined according to the degree of space charge (including the case where no space charge occurs) or the degree of measurement sensitivity degradation due to space charge (including the case where no sensitivity degradation occurs).

[0033] <Embodiment 1: Summary> The mass spectrometer 100 according to the first embodiment starts sampling of ion amount data at every same time interval Td, and determines the data collection time length Ti according to the degree of space charge or the degree of measurement sensitivity degradation due to space charge. Thereby, data collection can be terminated before sensitivity degradation occurs due to space charge generation. That is, the influence of sensitivity degradation due to space charge can be suppressed.

[0034] The mass spectrometer 100 according to the first embodiment determines the data collection time length Ti in the sampling to be performed this time according to the ion amount described in the sampling result of the ion amount data performed last time. By using the sampling result of the previous time, it is possible to appropriately determine the current Ti according to the assumption of whether the ion amount is excessive in the current sampling.

[0035] <Embodiment 2> In the first embodiment, it was described that the current data collection time length Ti is calculated according to the amount of ions sampled previously. This is to terminate sampling before the measurement sensitivity decreases when the amount of ions increases due to space charge. In the second embodiment of the present disclosure, another method for terminating sampling before the measurement sensitivity decreases will be described. The configuration of the mass spectrometer 100 is the same as in the first embodiment.

[0036] 8 is a flowchart illustrating the procedure for measuring the amount of ions by the mass spectrometer 100 in this embodiment 2. This flowchart is executed by the analysis control unit 104. Each step in FIG. 8 will be described below.

[0037] (Figure 8: Steps S301 to S302) S301 is the same as S201. The analysis control unit 104 repeats the following steps S303 to S305 until the maximum number of cycles nmax is reached (S302). The cycle number is represented by the variable n.

[0038] (Figure 8: Step S303) The analysis control unit 104 starts collecting ion amount data for cycle n. Collection ends when the sampled ion count reaches a threshold Y. Y is an ion count equivalent to or below the ion amount at which measurement sensitivity decreases due to space charge, and is defined in advance by experiment, etc. This makes it possible to end data collection (shorten the data collection time length in accordance with the ion amount) before a decrease in sensitivity due to space charge occurs, as in the first embodiment. This step also serves as the process of calculating the data collection time length Ti in the first embodiment.

[0039] (Figure 8: Steps S304 to S305) These steps are the same as S206 to S207.

[0040] <Embodiment 2: Summary> The mass spectrometer 100 according to the second embodiment terminates data collection when the ion count sampled from the ion amount data reaches or exceeds a threshold Y. By setting the threshold Y so as to terminate data collection before a decrease in sensitivity due to space charge occurs, the effect of the decrease in sensitivity due to space charge can be suppressed, as in the first embodiment. Furthermore, unlike the first embodiment, there is no need to calculate the data collection time length Ti, which simplifies the processing procedure.

[0041] <Third Embodiment> In the above embodiment, the remaining time Tr is increased by shortening the data collection time Ti according to the amount of ions. During the remaining time Tr, the analysis control unit 104 may perform, for example, the ion ejection process described in the above embodiment, or may acquire a mass spectrum of the sample to be measured. Alternatively, the user may set the process to be performed during the remaining time.

[0042] In the above embodiment, the step of calculating the data collection time length Ti is described as being performed within the wait time, but this step may also be performed within the remaining time Tr. However, if Td is constant, the wait time also occurs at predetermined intervals, so it is desirable to perform processing that should be performed at the same timing in each cycle within the wait time. For example, if it is desired to start the processing of calculating Ti at the same timing in each cycle, this can be performed within the wait time.

[0043] <Modifications of the present disclosure> The present disclosure is not limited to the above-described embodiments and includes various modifications. For example, the above-described embodiments have been described in detail to clearly explain the present disclosure, and it is not necessary to include all of the described configurations. Furthermore, a part of one embodiment can be replaced with a configuration of another embodiment. Furthermore, a configuration of another embodiment can be added to a configuration of one embodiment. Furthermore, a part of the configuration of each embodiment can be added to, deleted from, or substituted for a part of the configuration of another embodiment.

[0044] In the above embodiment, the data collection time length Ti is calculated based on the amount of ions sampled last time, but it may also be calculated based on the amount of ions sampled two or more times before. In other words, if the amount of ions sampled this time can be estimated based on the results of two or more previous samples, it is not necessary to use the results of the previous sample.

[0045] In the above embodiments, the data analysis unit 103 and the analysis control unit 104 can be configured using hardware such as a circuit device that implements these functions, or can be configured by having a computing device such as a CPU (Central Processing Unit) execute software that implements these functions. [Explanation of symbols]

[0046] 100: Mass spectrometer 101:Measurement part 102: Analog-to-digital converter (ADC) 103: Data Analysis Department 104: Analysis control unit 105a: Sample introduction tube 105b: Gas inlet 106: Vacuum chamber section 107a~d: Electrode 108a: Multipole ion guide 108b: Pre-filter 108c: Multipole mass filter 108d: Multipole postfilter 109: Ion detector

Claims

1. A control method comprising:

1. A method for controlling a mass spectrometer equipped with a pre-filter in front of a multipole mass filter, comprising: starting to collect data describing the results of measuring the amount of ions in a sample by the mass spectrometer; collecting the data that has started to be collected; and the step of starting to collect data is performed at identical time intervals; a time length for collecting the data in the data collecting step varies depending on the degree of space charge generated in the pre-filter or the degree of reduction in sensitivity of the mass spectrometer caused by the space charge; the control method further includes a step of causing the mass spectrometer to perform a process other than collecting the data during a remaining time before starting to collect the next data after the step of collecting the data is completed, The process other than collecting the data is a process of discharging ions accumulated in the pre-filter. A control method comprising:

2. The control method further comprises determining the time length; In the step of determining the time length, a parameter representing the amount of ions described by the data collected in the step of collecting data is obtained; In the step of determining the time length, the time length is determined according to the parameter.

2. The control method according to claim 1.

3. the parameter is the amount of the ion described by the data collected in at least one or more previous data collecting steps; When the time length determined according to the parameter is reached, the step of collecting the data is terminated and the timing for starting the next step of collecting the data is awaited.

3. The control method according to claim 2.

4. In the step of determining the time length, the time length is determined by referring to time length data describing a rule for determining the time length; The time length data is The greater the amount of ions, the shorter the time period. or When the amount of ions is less than a predetermined value, the time length is constant, and when the amount of ions is equal to or greater than the predetermined value, the time length becomes shorter as the amount of ions increases. The rule is written as follows:

4. The control method according to claim 3.

5. the parameter is the number of counts of the amount of ions in the step of collecting data; If the parameter reaches a threshold value in the step of collecting data, the step of collecting data is terminated at that point, and the timing for performing the step of starting to collect the next data is awaited.

3. The control method according to claim 2.

6. The control method further includes a step of waiting for timing to perform a next step of starting to collect the data after the step of collecting the data is completed, The step of determining the length of time is performed during the step of waiting.

3. The control method according to claim 2.

7. The process other than collecting the data is a process of acquiring a mass spectrum of the sample measured by the mass spectrometer.

2. The control method according to claim 1.

8. After the step of collecting the data is completed, the step of determining the time length is performed during the remaining time before the next collection of the data is started.

4. The control method according to claim 3.

9. A mass spectrometer equipped with a pre-filter in front of a multipole mass filter, A mass spectrometer comprising a controller that executes the control method according to claim 1.

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