Mass spectroscope

Abstract

To detect an ion amount with high accuracy in a wide concentration range even in the case where a detector voltage is changed.SOLUTION: A mass spectroscope comprises: a detector that generates a current pulse signal so as to correspond to an ion injected by a gain corresponding to a voltage; a voltage generation part that applies a voltage to the detector; a branch part that branches a voltage pulse signal on the basis of the current pulse signal fetched out from an anode of the detector; a pulse count part that detects one of the signals by a pulse count system; an analog detection part that detects the other of the signals by an analog detection system; a conversion information storage part that holds conversion information indicating a correspondence relation between a predetermined count value that a count value by the pulse part under the detector voltage at the measurement is in a non-saturated state and the analog detection value at the time; and a conversion counting value calculation part that calculates a conversion counting value by using the analog detection value at the time and the conversion information in the case where any one of the counting value obtained by the measurement and the analog detection value is larger than a predetermined value.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] The present invention relates to a mass spectrometer, and more particularly to an ion detection technique in a mass spectrometer.

Background Art

[0002] As an ion detector in a mass spectrometer, a secondary electron multiplier tube is widely used. The ion detection methods using a secondary electron multiplier tube are roughly classified into an analog detection method and a pulse count detection method.

[0003] The analog detection method obtains a DC voltage obtained by integrating a minute current pulse signal output from an ion detector as a detection value. This detection method can detect ions even when the gain of the ion detector is set low. Therefore, output saturation in the ion detector hardly occurs, which is advantageous for expanding the dynamic range when the component concentration of the detection target is high. On the other hand, since this detection method is easily affected by electrical noise, it is disadvantageous in terms of the S / N ratio when the component concentration of the detection target is low.

[0004] On the other hand, the pulse count detection method amplifies a minute current pulse signal output from an ion detector, and counts a pulse signal of a predetermined pulse height value generated by comparing it with a predetermined threshold value in a comparator as a detection value. In this detection method, since it is not affected by electrical noise smaller than the predetermined threshold value, it is advantageous in terms of the S / N ratio in the low concentration region. However, due to constraints such as the pulse width of the minute current pulse signal output from the ion detector (usually about 10 nsec) and the dead time in the subsequent waveform processing circuit, when the amount of ions incident on the ion detector is large, counting omission occurs. Therefore, there is a limit to the dynamic range in the high concentration region.

[0005] For example, mass spectrometers used in liquid chromatography-mass spectrometry (LC-MS) require high quantitative performance for trace components. Such mass spectrometers typically employ pulse counting, which offers excellent ion detection accuracy in low-concentration ranges. However, a common problem with conventional pulse counting is its narrow dynamic range. For this reason, techniques have been proposed to expand the dynamic range in high-concentration ranges when using pulse counting.

[0006] Patent Document 1 discloses a method for expanding the dynamic range in the high-concentration region in a pulse count detection method by correcting the pulse count value using a dead time correction coefficient corresponding to the count rate.

[0007] Furthermore, in the ion detection system disclosed in Patent Document 2, an amplifier for pulse count detection and an amplifier for analog detection are connected in parallel to the current signal output terminal of the secondary electron multiplier tube, and pulse count detection and analog detection are performed in parallel regardless of the magnitude of the output of the secondary electron multiplier tube. When the amount of ions is small and the output voltage of the amplifier for analog detection is below a predetermined value, the detection value obtained by the pulse count detection method is used. On the other hand, when the amount of ions increases and the output voltage of the amplifier for analog detection exceeds a predetermined value, the detection value obtained by the analog detection method is used. The ratio between the analog detection value and the pulse count value is stored in advance as a conversion coefficient inside the CPU, and the analog detection value is converted to a pulse count value using this conversion coefficient. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] U.S. Patent No. 9991104 [Patent Document 2] Japanese Patent Application Publication No. 6-181046 [Patent Document 3] Japanese Patent Publication No. 2011-14481 [Patent Document 4] U.S. Patent Application Publication No. 20150325420 [Overview of the project] [Problems that the invention aims to solve]

[0009] According to the method described in Patent Document 1, it is possible to expand the dynamic range of the pulse count method even when the amount of ions incident on the ion detector increases to a certain extent. However, if the amount of ions incident on the ion detector increases further and the multiple pulse signals output from the ion detector become completely inseparable in the time direction, and the pulse count value saturates, correction becomes impossible. In other words, the expansion of the dynamic range in the high-concentration region by this method is limited by the fundamental limitations of pulse count detection.

[0010] In contrast, in the method described in Patent Document 2, when the amount of ions incident on the ion detector is large, the detection value obtained by the pulse count detection method is substantially unused. Therefore, unlike the method described in Patent Document 1, it is not affected by the saturation of the pulse count value. However, this method has the following problems.

[0011] The gain of an ion detector, such as a secondary electron multiplier tube, depends on the detector voltage applied to the ion detector. As disclosed in Patent Document 3, in pulse count detection methods, the detector voltage is generally set within a plateau region where the pulse count value is approximately flat with respect to changes in the detector voltage. On the other hand, in analog detection methods, the higher the gain of the ion detector, that is, the higher the detector voltage, the larger the detected value becomes, and saturation is more likely to occur in the high-concentration region. Therefore, if you want to ensure a dynamic range in the high-concentration region, it is better not to set the detector voltage too high. For these reasons, the detector voltage can be changed as appropriate by manual adjustment or automatic tuning by the user. If the gain of the ion detector changes due to a change in the detector voltage, it becomes impossible to obtain an accurate pulse count value from the analog detected value even using the conversion coefficient stored in the CPU.

[0012] This invention was made to solve these problems, and one of its main objectives is to provide a mass spectrometer that can accurately detect the amount of ions over a wide concentration range, from low to high concentrations, even when the detector voltage applied to the ion detector is changed. [Means for solving the problem]

[0013] One embodiment of the mass spectrometer according to the present invention, which was made to solve the above problems, is: An ion detector that generates a current pulse signal corresponding to incident ions with a gain corresponding to the detector voltage, A voltage generating unit that supplies a detector voltage to the ion detector, A branching unit that branches a voltage pulse signal based on a current pulse signal extracted from the anode of the ion detector into multiple branches, A pulse counting unit detects one of the voltage pulse signals branched by the aforementioned branching unit using a pulse counting method and outputs a pulse count value. An analog detection unit detects the other voltage pulse signal branched by the aforementioned branching unit using an analog detection method and outputs an analog detection value. A conversion information storage unit holds conversion information that indicates the correspondence between a predetermined pulse count value and the analog detection value at a time when the pulse count value by the pulse count unit is non-saturated, under the detector voltage supplied from the voltage generation unit to the ion detector during measurement execution. A converted count value calculation unit calculates a converted count value as a replacement for the pulse count value obtained by the pulse count unit when either the pulse count value obtained by the pulse count unit or the analog detection value obtained by the analog detection unit is greater than a predetermined value, using the analog detection value at that time and the conversion information stored in the conversion information storage unit. It is equipped with. [Effects of the Invention]

[0014] According to the above aspect of the mass spectrometer according to the present invention, even when the detector voltage is changed to change the gain of the ion detector, the conversion information corresponding to the detector voltage after the change is used to accurately obtain the converted count value from the analog detection value. As a result, even when the detector voltage is changed, ions can be accurately detected over a wide concentration range from low concentration to high concentration, and a detection value corresponding to the amount of ions can be obtained.

Brief Description of the Drawings

[0015] [Figure 1] Schematic block diagram of a mass spectrometer according to an embodiment of the present invention. [Figure 2] Schematic block diagram of an ion detector and a detection value generation unit in the mass spectrometer of the present embodiment. [Figure 3] Diagram showing an example of the relationship between the amount of incident ions on an ion detector, the pulse count value, and the analog detection value based on an actual measurement example. [Figure 4] Diagram showing the relationship between the amount of incident ions on an ion detector and the pulse count value in the mass spectrometer of the present embodiment. [Figure 5] Diagram showing an example of the relationship between the detector voltage and the pulse count value. [Figure 6] Diagram showing the relationship between the plateau region and the range where the desired dynamic range upper limit can be obtained. [Figure 7] Diagram showing the relationship between the detector voltage corresponding to each mode and the plateau region in the mass spectrometer of the present embodiment. [Figure 8] Diagram showing an example of each mode, the detector voltage, and the conversion coefficient. [Figure 9] Diagram showing an actual measurement example of a chromatogram by LC-MS using the mass spectrometer of the present embodiment. [Figure 10] Diagram showing an example of an ideal chromatographic peak by LC-MS using the mass spectrometer of the present embodiment. [Figure 11] Diagram showing an example of a chromatographic peak when the ion detector deteriorates in LC-MS using the mass spectrometer of the present embodiment. [Figure 12] A schematic block diagram of the ion detector and detection value generation unit in a mass spectrometer, which is one modified example. [Figure 13] This figure shows an example of a chromatographic peak obtained using LC-MS with a mass spectrometer, which is one variation of the method. [Modes for carrying out the invention]

[0016] [Mass spectrometer according to one embodiment] A mass spectrometer, which is one embodiment of the present invention, will be described with reference to the attached drawings.

[0017] Figure 1 is a schematic block diagram of the mass spectrometer of this embodiment, and Figure 2 is a schematic block diagram of the detection value generation unit 4 in Figure 1. As shown in Figure 1, this mass spectrometer comprises an ion source 1, a mass separation unit 2, an ion detector 3, a detection value generation unit 4, a data processing unit 5, a voltage generation unit 6, a control unit 7, an operation unit 8, and a display unit 9.

[0018] Ion source 1 ionizes the components (compounds) in the introduced sample. The ionization method is not particularly restricted. If the sample is a liquid, methods such as electro-ion spray ionization or atmospheric pressure chemical ionization can be used. If the sample is a gas, methods such as electron ionization or chemical ionization can be used. In addition, ionization methods using laser light or electron beams, such as matrix-assisted laser desorption ionization, can also be used.

[0019] Ions derived from the sample components generated in ion source 1 are introduced into mass separation unit 2, where the ions are separated according to their mass-to-charge ratio (m / z). The method and configuration of mass separation unit 2 are not particularly limited. For example, a quadrupole mass filter, a time-of-flight mass separator, or an ion trap can be used as mass separation unit 2. Furthermore, mass separation unit 2 may also have a function to dissociate ions and generate product ions. That is, a triple quadrupole configuration including a collision cell that dissociates ions by collision-induced dissociation, or a configuration in which ion selection and ion dissociation are performed together with an ion trap is also acceptable.

[0020] Ions separated according to their m / z in the mass separation unit 2 are incident on the ion detector 3. The ion detector 3 outputs a minute current pulse signal corresponding to each incident ion. The ion detector 3 can typically include a conversion dynode and a secondary electron multiplier tube.

[0021] The detection value generation unit 4, as will be described in detail later, generates detection values ​​corresponding to the amount of ions incident on the ion detector 3 by performing predetermined processing on the minute pulse signal output from the ion detector 3. The data processing unit 5 receives the detection values ​​from the detection value generation unit 4 and performs predetermined data processing. For example, the data processing unit 5 can create a mass spectrum over a predetermined m / z range based on the detection values ​​obtained when an m / z scan over a predetermined m / z range is performed in the mass separation unit 2.

[0022] The voltage generation unit 6, under the control of the control unit 7, applies predetermined voltages to the ion source 1, the mass separation unit 2, and the ion detector 3, respectively, thereby performing the mass spectrometry operation described above. The control unit 7 performs this control for mass spectrometry and includes, as characteristic functional blocks, a mode selection reception unit 70, a parameter adjustment control unit 71, and a conversion coefficient determination unit 72.

[0023] Furthermore, the data processing unit 5 and the control unit 7 utilize a personal computer as a hardware resource, and by executing dedicated control and processing software installed on the personal computer on that computer, the functional blocks included in the data processing unit 5 and the control unit 7 can be realized.

[0024] As shown in Figure 2, the detection value generation unit 4 includes a transimpedance amplifier 40, a signal branching unit 41, an integrating circuit 42, a comparator 43, an analog-to-digital converter (ADC) 44, a counting unit 45, and a dynamic range (DR) expansion processing unit 46. The DR expansion processing unit 46 includes, as functional blocks, a conversion coefficient storage unit 461, a conversion count value calculation unit 462, and a detection value selection unit 463.

[0025] The gain of the secondary electron multiplier tube constituting the ion detector 3 depends on the detector voltage Vd applied from the voltage generation unit 6. Typically, this detector voltage Vd is set to a gain that allows the voltage pulse signal originating from the minute current pulse signal output from the anode 30 of the ion detector 3 to be appropriately detected by the pulse count detection method. Further details will be described later.

[0026] When ions are incident on the ion detector 3 while this detector voltage is applied, a minute current pulse signal is output from the anode 30 accordingly. This current pulse signal is converted from current to voltage in the transimpedance amplifier 40 to become a voltage pulse signal. The value of the resistor that determines the gain of the transimpedance amplifier 40 can be appropriately selected within a range of approximately 1 kΩ to 50 kΩ. Normally, the pulse width of the current pulse signal output from the secondary electron multiplier tube is narrow, about 5 to 10 nsec, so it is best to select a resistor value that can amplify this high-speed pulse signal waveform without degrading it as much as possible for accurate pulse counting in the subsequent stage. Note that existing transimpedance amplifiers such as those described in Patent Document 4 can be used as the transimpedance amplifier 40.

[0027] The voltage pulse signal output from the transimpedance amplifier 40 is split into two paths at the signal branching unit 41. One path is input to one input terminal of the comparator 43, and the other is input to the integrating circuit 42. A predetermined threshold voltage Vth is input to the other input terminal of the comparator 43. The comparator 43 compares the voltage pulse signal with the threshold voltage Vth, and outputs a pulse signal with a predetermined peak value when the former is greater than or equal to the latter. The peak value of the voltage pulse signal input to the comparator 43 changes, but if the peak value exceeds the threshold voltage Vth, the output of the comparator 43 becomes a binary signal, i.e., a digital signal, with a constant peak value. This binary pulse signal is input to the counting unit 45, which counts the pulse signals input within a unit time and outputs a count value. The counting unit 45 is reset after each unit of time has elapsed. This count value is the detected value by the pulse count detection method.

[0028] Meanwhile, the integrating circuit 42 outputs an analog voltage value by integrating and amplifying the input voltage pulse signal over a unit time. This analog voltage value is also reset after each unit of time has elapsed. The analog voltage value output from the integrating circuit 42 is digitized by the analog-to-digital conversion unit 44. The above analog voltage value is a value detected by an analog detection method, but here, the value obtained by digitizing this analog voltage value is also referred to as an analog detection value.

[0029] The upper limit of the output voltage of the integrating circuit 42 is limited by the power supply voltage of the amplifier constituting the integrating circuit 42, and this upper limit is usually in the range of 3.3V to 15V. Therefore, the gain of the integrating circuit 42 should be appropriately designed so that the output voltage of the integrating circuit 42 does not saturate at the desired ion amount. As an example, in the mass spectrometer of this embodiment, an operational amplifier with an output voltage of 5Vmax is used in the integrating circuit 42, and 3e8 (=3 × 10) corresponding to the target upper limit of the dynamic range is used. 8 The gain of the integrating circuit 42 is set so that the output voltage is 3V at an ion concentration of )[cps].

[0030] As described above, in the mass spectrometer of this embodiment, based on a minute current pulse signal output from a single anode 30 in the ion detector 3, detection operations using an analog detection method and detection operations using a pulse count detection method are performed in parallel, and both detection values, i.e., pulse count values ​​and analog detection values, are obtained.

[0031] In the configuration shown in Figure 2, it is theoretically possible to split the signal at the input stage of the transimpedance amplifier 40. However, in that case, the output current from the ion detector 3 is split into a pulse count side and an analog detection side, which is disadvantageous in terms of the signal-to-noise ratio and other factors. In contrast, in this embodiment, the current signal is converted to a voltage signal in the transimpedance amplifier 40 and then the voltage signal is split, thus avoiding a decrease in signal quality due to splitting.

[0032] The DR expansion processing unit 46 uses the two detected values ​​mentioned above to obtain a detected value with an expanded dynamic range compared to the pulse count detection method. The principle of this DR expansion will now be explained.

[0033] Figure 3 is a schematic diagram showing an example of the relationship between the amount of ions incident on the ion detector 3, the pulse count value, and the analog detection value. As shown in Figure 3(A), in this example, the relationship between the ion amount and the pulse count value is almost linear in the range of 1e7 [cps] or less, but beyond 1e7 [cps], ion counting errors occur. In contrast, as shown in Figure 3(B), the relationship between the ion amount and the analog detection value is almost linear up to the ion amount corresponding to 3e8 [cps], where the ion detector 3 itself becomes saturated.

[0034] As already mentioned, the pulse count detection method offers a better signal-to-noise ratio (SNR) when the ion quantity is low. Therefore, in the mass spectrometer of this embodiment, as shown in Figure 4, the pulse count value is used directly within the range of ion quantities in which accurate pulse counting is possible (1e7 [cps] or less), and the dynamic range of the detected value is expanded by using the analog detected value for ion quantities exceeding that range. In the range of ion quantities in which the analog detected value is used, the converted count value obtained by multiplying the measured analog detected value by a conversion factor previously acquired by measuring ion quantities in which the pulse count does not saturate (i.e., no counting errors occur) is used. For example, if the analog detected value is 0.1V when the pulse count value is 1e7 [cps], the conversion factor is 1e7 [cps] / 0.1 [V] = 1e6.

[0035] In the mass spectrometer of this embodiment, the conversion coefficient calculated by the conversion coefficient determination unit 72 of the control unit 7 based on measurements of a standard sample performed, for example, at the time of tuning the instrument as described later, is stored in the conversion coefficient storage unit 461. However, this conversion coefficient can also be experimentally determined by the instrument manufacturer and stored in the conversion coefficient storage unit 461. In that case, the conversion coefficient determination unit 72 is not necessary.

[0036] When measuring a sample, the analog detection value and the pulse count value are input to the DR expansion processing unit 46 in parallel, as described above, in response to the ions entering the ion detector 3. The converted count value calculation unit 462 determines whether the pulse count value (or analog detection value) is greater than or equal to a predetermined value. If the pulse count value (or analog detection value) is greater than or equal to the predetermined value, the converted count value is obtained by multiplying the analog detection value by the conversion coefficient read from the conversion coefficient storage unit 461. The detection value selection unit 463 outputs the pulse count value as the detection value if it is less than the predetermined value, and outputs the converted count value calculated by the converted count value calculation unit 462 as the detection value instead of the pulse count value if it is otherwise.

[0037] As a result, as shown in Figure 4, depending on the amount of ions incident on the ion detector 3, the pulse count value, or the converted count value calculated using the analog detection value and a conversion coefficient, is selectively output as the detection value.

[0038] The dynamic range of the detected value at this time is limited by the saturation of the output current of the ion detector 3. This saturation of the ion detector 3 is more likely to occur when the gain of the ion detector 3, that is, the detector voltage Vd applied from the voltage generation unit 6, is high. Therefore, from the perspective of expanding the upper limit of the dynamic range, a lower detector voltage is preferable. On the other hand, in order to perform pulse counting without missing any counts, it is necessary to set the gain of the ion detector 3 so that the voltage pulse signal derived from the current pulse signal output from the ion detector 3 reliably exceeds the threshold voltage Vth, and for this purpose, the detector voltage needs to be set higher. In other words, there is a trade-off relationship when setting the detector voltage of the ion detector 3 between preventing missing pulse counts (i.e., ensuring sensitivity) and expanding the dynamic range.

[0039] Figure 5 shows an example of the relationship between detector voltage and pulse count value, known as a plateau curve. Generally, in mass spectrometers, these characteristics are examined during tuning, and the detector voltage is set to a plateau region where the pulse count value is roughly flat. Also, since a lower detector voltage is better for extending the lifespan of the secondary electron multiplier tube, the detector voltage is usually set to a relatively low value within the plateau region (for example, the value of point U shown in Figure 5). However, it is unclear whether the desired dynamic range can be obtained at the detector voltage set at this time, and such consideration is not usually given.

[0040] In contrast, the mass spectrometer of this embodiment sets a limit (upper limit) on the detector voltage setting so that the ion detector 3 does not saturate at the upper limit of the desired dynamic range. For example, if the amount of ions equivalent to 3e8 [cps] is to be set as the upper limit of the dynamic range, the parameter adjustment control unit 71 stores the corresponding analog detection value (e.g., 3V) internally and sets the detector voltage within the plateau region so that the ratio of the pulse count value and the analog detection value when the detector voltage is changed is within a predetermined range (e.g., 3e8 [cps] / 3 [V] or less) (see Figure 6). This ensures that the upper limit of the dynamic range is reliably set to the desired value.

[0041] However, depending on the characteristics of the secondary electron multiplier tube, it may not be possible to set the detector voltage under the conditions described above. Specifically, for example, if the plateau curve shifts to the high-voltage side due to individual differences in the device, such as a high noise level, the voltage corresponding to the upper limit of the desired dynamic range may fall below the lower limit of the plateau region. In this case, if the detector voltage is set within the range of the plateau region in order to perform counting without missing any counts, the upper limit of the dynamic range will become lower than the desired value. Therefore, the mass spectrometer of this embodiment is provided with three detector operating modes, namely sensitivity priority mode, balance mode, and dynamic range priority mode, each with different detector voltages, and the user can select one of them in advance.

[0042] Figure 7 shows the detector voltage values ​​corresponding to the three detector operating modes on the plateau curve. Figure 8 shows an example of detector voltage values ​​and conversion factors corresponding to the three detector operating modes. As shown in Figure 7, the detector voltage V2 corresponding to the balanced mode is near the lower limit of the plateau region, and the detector voltage V1 corresponding to the sensitivity priority mode is greater than V2 and within the range of the plateau region. On the other hand, the detector voltage V3 corresponding to the dynamic range priority mode is smaller than V2 and deviates from the range of the plateau region.

[0043] In the plateau region, the pulse count value hardly increases even when the detector voltage increases, while the analog detection value increases. Therefore, the higher the detector voltage is set within the plateau region, the narrower the dynamic range of the detector becomes. For this reason, although the dynamic range is slightly narrower in sensitivity priority mode compared to other modes, a voltage pulse signal that reliably exceeds the threshold voltage Vth in response to ions incident on the ion detector 3 can be obtained, thus achieving high sensitivity. Conversely, in dynamic range priority mode, although the voltage pulse signal may not exceed the threshold voltage Vth even when ions are incident on the ion detector 3, which is disadvantageous in terms of sensitivity, the upper limit of the dynamic range can be expanded compared to other modes.

[0044] The conversion factor determination unit 72 determines a conversion factor corresponding to each of the three detector operating modes, for example, when tuning the device, and the conversion factor storage unit 461 stores the conversion factor according to the mode. When a user performs a predetermined operation on the operation unit 8 during measurement, the mode selection reception unit 70 displays a screen on the display unit 9 for selecting one of the three detector operating modes. When the user selects one of the modes using the operation unit 8 after viewing this screen, the mode selection reception unit 70 determines the detector voltage in response to that operation. The voltage generation unit 6, having received an instruction for the detector voltage from the control unit 7, generates a DC voltage according to the instruction and applies it to the ion detector 3 as the detector voltage Vd. This determines the gain of the ion detector 3.

[0045] Furthermore, the control unit 7 sends information about the selected mode to the DR expansion processing unit 46. The converted count value calculation unit 462 then obtains the conversion coefficient corresponding to the specified mode from the conversion coefficient storage unit 461 and calculates the converted count value by multiplying the analog detection value obtained during measurement by this conversion coefficient. In this way, regardless of which detector operating mode is selected, a highly accurate converted count value can be obtained from the analog detection value using the conversion coefficient corresponding to the selected mode.

[0046] In the mass spectrometer of this embodiment, since the conversion coefficient can be stored in the conversion coefficient storage unit 461 at any time before the measurement is executed, as described above, the device manufacturer may experimentally obtain the conversion coefficient and store it in the conversion coefficient storage unit 461 before providing this device to the user. However, the characteristics of the ion detector 3 and the like may change with the use of the device, and accordingly, the appropriate conversion coefficient may also change. Therefore, when adjusting the voltages applied to, for example, a plurality of ion transport optical systems, a quadrupole mass filter, and the ion detector 3 in the device to an optimal state, the conversion coefficient in the adjusted state is obtained and stored in the conversion coefficient storage unit 461 for use in subsequent measurements.

[0047] Specifically, when the user performs a predetermined operation from the operation unit 8 at an appropriate time, the parameter adjustment control unit 71 executes an auto-tuning operation for adjusting parameters such as the applied voltage to each predetermined part while repeating the measurement using the standard sample. This auto-tuning operation may be automatically performed, for example, when the device is started up, or may be automatically performed at a specified timing, such as every time the device is used for a predetermined period.

[0048] During the auto-tuning operation, the parameter adjustment control unit 71 obtains the pulse count value for the standard sample while changing the detector voltage applied to the ion detector 3 in a predetermined step width, thereby obtaining a plateau curve. Then, the range of the plateau region is determined from the obtained plateau curve. For example, the lower limit of the plateau region is defined as V2, V1 (> V2) is defined within the range where the desired dynamic range can be obtained, and V3 (< V2) is defined at a position of a count value that is a predetermined ratio lower than the pulse count value in the plateau region. In this way, the detector voltage corresponding to each detector operation mode can be determined. Further, the conversion coefficient determination unit 72 can determine the conversion coefficient from the determined detector voltages and pulse count values.

[0049] It is possible to recalculate the detector voltage and conversion factor by finding the plateau curve each time the device is retuned, but it is not necessary to recalculate them every time the device is tuned. For example, the detector voltage and conversion factor may be recalculated each time the device is tuned a predetermined number of times, or the detector voltage and conversion factor may be recalculated when the usage time of the device exceeds a specified time since the last reset of the detector voltage and conversion factor.

[0050] [Example of actual measurement] Figure 9 shows an example of a chromatogram obtained when a high-concentration liquid sample is repeatedly introduced 10 times by flow injection analysis into the mass spectrometer of this embodiment. The sample concentration is such that the pulse count value saturates. As shown in Figure 9, in the conventional pulse count detection method, the detected value saturates at an ion concentration of around 5e7 [cps]. In contrast, the method in the mass spectrometer of this embodiment shows that ion concentrations exceeding 2e8 [cps] are detected well. Thus, the mass spectrometer of this embodiment can expand the dynamic range of the detected value in the high-concentration region.

[0051] [Challenges during ion detector degradation] In the mass spectrometer of the above embodiment, the threshold for switching the detection value is set to 1e7 [cps] in terms of ion amount. When the pulse count value is 1e7 [cps] or less, the pulse count value is used as is, and when the pulse count value exceeds 1e7 [cps], the converted count value is used. Figure 10 shows the chromatographic peak when a sample with an ion amount exceeding 1e7 [cps] is introduced. If the conversion factor is set appropriately, the pulse count value and the converted count value connect smoothly, as shown in Figure 10. This results in good quantitative accuracy when calculating component concentrations using, for example, peak area values.

[0052] However, as the secondary electron multiplier tube deteriorates with prolonged use, the output current signal for a given ion quantity decreases, potentially leading to an inappropriate conversion factor. When the converted count value is calculated using the conversion factor acquired before the deterioration of the secondary electron multiplier tube, the chromatographic peak becomes distorted at the boundary between the pulse count value and the converted count value, as shown in Figure 11. This distortion results in a decrease in the quantitative accuracy of component concentrations.

[0053] As mentioned above, when the conversion factor is recalculated and the stored information is updated through instrument tuning, increasing the frequency of this update can avoid the distortion of chromatographic peaks described above. However, since the measurement of standard samples is repeated during instrument tuning, contamination of the ion transport optical system and other components is likely to occur. Furthermore, frequent tuning increases the burden on the user and is undesirable in terms of the actual operating efficiency of the instrument. Therefore, in order to always obtain the converted count value using the latest conversion factor without increasing the frequency of instrument tuning, the mass spectrometer can be configured as shown in the following modified example.

[0054] [Differentiation] Figure 12 is a schematic block diagram of the ion detector and detection value generation unit in a modified mass spectrometer. Components identical to those shown in Figure 2 are denoted by the same reference numerals, and detailed explanations are omitted. In this mass spectrometer, the DR expansion processing unit 46 includes a conversion coefficient calculation unit 460 as a functional block. In the mass spectrometer of the above embodiment, the conversion coefficient is stored in the conversion coefficient storage unit 461 at least at the stage when measurement is performed on the target sample. In contrast, in this mass spectrometer, when measurement is performed on the target sample, the conversion coefficient calculation unit 460 calculates the conversion coefficient using data in which the ionic intensity is less than or equal to a predetermined value, and stores the obtained conversion coefficient in the conversion coefficient storage unit 461. Then, the conversion count value calculation unit 462 calculates the conversion count value from the pulse count value based on that conversion coefficient. In other words, the conversion coefficient is determined while the measurement is being performed, and the conversion count value is calculated using that conversion coefficient.

[0055] For example, as time progresses during measurement, the ion intensity (pulse count value) increases as shown in Figure 11. When the pulse count reaches a predetermined value (data point P in Figure 11) below 1e7 [cps], where it does not saturate, the conversion factor calculation unit 460 acquires the pulse count value and analog detection value at that point. It then calculates the ratio to obtain the latest conversion factor. The conversion factor obtained in this way is a more accurate conversion factor that reflects the state of degradation of the ion detector 3 at the time the data was acquired. This conversion factor is immediately stored in the conversion factor storage unit 461, and as shown in Figure 11, when the measured ion intensity exceeds 1e7 [cps], the converted count value obtained from the analog detection value using that conversion factor is adopted as the detector value. Normally, the detector voltage is not changed during measurement, so the conversion factor used is the conversion factor under the detector voltage applied to the ion detector 3 when the analog detection value, which is the subject of the conversion process, is obtained. As a result, an appropriate conversion is performed that reflects the degradation state of the ion detector 3, and as shown in Figure 13, the chromatic peaks are generally smoothly connected above and below the threshold of 1e7 [cps]. In other words, the distortion of the chromatic peaks is reduced.

[0056] In the above explanation, the conversion factor is calculated virtually in real time during the measurement, and the converted count value is calculated using that conversion factor. Therefore, for example, when displaying the chromatogram on the screen of the display unit 9 in near real time during the measurement, it is possible to depict a virtually distortion-free chromatographic peak corrected using an appropriate conversion factor.

[0057] Alternatively, the conversion process may not be performed during measurement. Instead, the conversion factor may be determined by post-processing after the measurement is complete. This conversion factor can then be used to calculate the converted count value from the analog detection value, and the data constituting the chromatographic peak may be replaced. In this case, for example, the conversion factor can be calculated from a large number of data points included in the range Q where the ion intensity is 1e7 [cps] or less, as shown in Figure 11. Therefore, compared to determining the conversion factor in near real-time as described above, this method has the advantage of improving the accuracy of the conversion factor itself, and thus improving the accuracy of the conversion using it, i.e., the accuracy of the obtained converted count value.

[0058] It should be noted that the mass spectrometers in the above embodiments and modified examples are merely examples of the present invention, and any modifications, alterations, or additions made within the scope of the present invention will naturally be included within the scope of the claims of this patent application.

[0059] [Various forms] Those skilled in the art will understand that the exemplary embodiments described above are specific examples of the following embodiments.

[0060] (Section 1) One embodiment of the mass spectrometer according to the present invention is: An ion detector that generates a current pulse signal corresponding to incident ions with a gain corresponding to the detector voltage, A voltage generating unit that supplies a detector voltage to the ion detector, A branching unit that branches a voltage pulse signal based on a current pulse signal extracted from the anode of the ion detector into multiple branches, A pulse counting unit detects one of the voltage pulse signals branched by the aforementioned branching unit using a pulse counting method and outputs a pulse count value. An analog detection unit detects the other voltage pulse signal branched by the aforementioned branching unit using an analog detection method and outputs an analog detection value. A conversion information storage unit holds conversion information that indicates the correspondence between a predetermined pulse count value and the analog detection value at a time when the pulse count value by the pulse count unit is non-saturated, under the detector voltage supplied from the voltage generation unit to the ion detector during measurement execution. A converted count value calculation unit calculates a converted count value as a replacement for the pulse count value obtained by the pulse count unit when either the pulse count value obtained by the pulse count unit or the analog detection value obtained by the analog detection unit is greater than a predetermined value, using the analog detection value at that time and the conversion information stored in the conversion information storage unit. It is equipped with.

[0061] According to the mass spectrometer described in paragraph 1, even if the detector voltage is changed to alter the gain of the ion detector, the converted count value can be determined with high accuracy from the analog detected value by utilizing the conversion information corresponding to the changed detector voltage. As a result, even when the detector voltage is changed, ions can be detected accurately over a wide concentration range from low to high concentrations, and a detected value corresponding to the amount of ions can be obtained.

[0062] (Section 2) In the mass spectrometer described in Section 1, The conversion information storage unit holds a plurality of conversion information corresponding to a plurality of detector voltage values ​​that are different from each other, The converted count value calculation unit may selectively acquire conversion information from the conversion information storage unit that corresponds to one of the plurality of detector voltage values ​​given to the ion detector during measurement, and calculate the converted count value using the acquired conversion information.

[0063] Since the gain of an ion detector depends on the detector voltage, the saturation of the pulse count value in the pulse count detection method and the saturation of the output of the ion detector itself also depend on the detector voltage. Therefore, it may be necessary to change the detector voltage through intentional adjustment, or the detector voltage may be changed by automatic adjustment. When the gain of the ion detector changes, the relationship between the pulse count value and the analog detection value also changes, and therefore the conversion factor also changes. In contrast, with the mass spectrometer described in Section 2, by preparing conversion factors corresponding to each of the multiple selectable detector voltage values, the converted count value can be accurately determined using the appropriate conversion factor corresponding to the detector voltage at that time.

[0064] (Section 3) The mass spectrometer described in Section 2 is: A mode selection section displays multiple selectable modes, including sensitivity priority mode and dynamic range priority mode, and accepts the user's selection of a mode. A control unit has a function to change the detector voltage supplied to the ion detector according to the mode selected by the mode selection unit, and when the dynamic range priority mode is selected, it sets a detector voltage lower than when the sensitivity priority mode is selected. Furthermore, The converted count value calculation unit may calculate the converted count value by obtaining conversion information corresponding to the detector voltage according to the mode selected by the mode selection unit from the conversion information storage unit.

[0065] In the mass spectrometer described in Section 3, when the sensitivity priority mode is selected, the detector voltage is set relatively high, which makes saturation of the analog detection value more likely in the high-concentration region. However, the increased gain of the ion detector reduces the likelihood of missing pulse counts in the low-concentration region, resulting in high detection sensitivity. On the other hand, when the dynamic range priority mode is selected, saturation of the analog detection value becomes less likely in the high-concentration region, and the dynamic range of the detection value is expanded. Thus, with the mass spectrometer described in Section 3, users can select measurements with high detection sensitivity or a wide dynamic range depending on the purpose of the measurement and the concentration of the sample being measured.

[0066] (Article 4) The mass spectrometer described in any one of paragraphs 1 to 3 is: A saturation reference value storage unit stores a saturation reference value related to the analog detection value when saturation occurs in the output of the ion detector, A detector voltage adjustment unit adjusts the detector voltage applied to the ion detector based on the pulse count value so that the analog detection value output from the analog detection unit does not exceed the saturation reference value, It can be further equipped with these features.

[0067] According to the mass spectrometer described in Section 4, the detector voltage can be adjusted so that the desired upper limit of the dynamic range is reliably achieved.

[0068] (Section 5) The mass spectrometer described in Section 1 is: When the pulse count value obtained by the pulse count unit is non-saturated and both the pulse count value and the corresponding analog detection value are obtained, the conversion information acquisition unit calculates conversion information using the pulse count value and the analog detection value and stores it in the conversion information storage unit. It can be further equipped with these features.

[0069] (Item 6) In the mass spectrometer described in Item 5, The conversion information acquisition unit calculates the conversion information during measurement and stores it in the conversion information storage unit. The converted count value calculation unit may, during the execution of the measurement, after the conversion information has been stored in the conversion information storage unit, output a converted count value calculated using the analog detection value at that time and the conversion information held in the conversion information storage unit, as a detection value to replace the pulse count value from the pulse count unit, if either the pulse count value obtained by the measurement from the pulse count unit or the analog detection value from the analog detection unit is greater than a predetermined value.

[0070] In the mass spectrometer described in Section 6, the converted count value is calculated using conversion information derived from data acquired during the measurement, rather than conversion information prepared before the measurement. Therefore, with the mass spectrometer described in Section 6, the conversion information reflects the state of the ion detector at the time of measurement, i.e., the degradation state and the detector gain corresponding to the detector voltage, allowing for a more accurate calculation of the converted count value. As a result, for example, when creating a chromatogram in which the ion intensity changes over time, the curve connection at the boundary between the detected value using pulse count values ​​and the detected value using converted count values ​​improves, and the quantitative accuracy when calculating component concentrations based on the area of ​​chromatographic peaks improves.

[0071] (Section 7) Furthermore, in the mass spectrometer described in Section 5, The conversion information acquisition unit calculates conversion information using the pulse count value and analog detection value obtained in the measurement after the measurement is performed and stores it in the conversion information storage unit. The converted count value calculation unit may calculate a converted count value using the analog detection value and the converted information held in the converted information storage unit if, after the conversion information has been stored in the converted information storage unit, either the pulse count value obtained by the pulse count unit through measurement or the analog detection value obtained by the analog detection unit is greater than a predetermined value.

[0072] Unlike the mass spectrometer described in Section 6, the mass spectrometer described in Section 7 calculates conversion information based on the data acquired during the measurement, not during the measurement, but after the measurement is performed, and uses this conversion information to calculate the converted count value. Therefore, in the mass spectrometer described in Section 7, the conversion information reflects the state of the ion detector at the time of measurement, i.e., the degradation state and the detector gain corresponding to the detector voltage, allowing for a more accurate calculation of the converted count value. As a result, for example, when creating a chromatogram in which the ion intensity changes over time, the connection of the curve at the boundary between the detected value using pulse count values ​​and the detected value using converted count values ​​becomes better, improving the quantitative accuracy when calculating component concentrations based on the area of ​​chromatographic peaks.

[0073] Furthermore, with the mass spectrometer described in Section 7, it is easy to calculate conversion information using a large amount of data obtained when the pulse count value from the pulse counting unit is in a non-saturated state. This allows for more accurate determination of the converted count value and further improves quantitative accuracy. [Explanation of symbols]

[0074] 1…Ion source 2...Mass separation section 3…Ion detector 30... Anode 4...Detection value generation unit 40…Transimpedance amplifier 41... Signal branching point 42...Integrator circuit 43... Comparator 44…Analog-to-digital conversion section 45…Counting section 46...DR Enlargement Processing Unit 461...Conversion factor storage unit 462...Conversion count value calculation unit 463...Detection value selection section 5…Data Processing Unit 6…Voltage generation unit 7…Control Unit 70...Mode selection reception section 71...Parameter adjustment control unit 72...Conversion factor determination unit 8...Operation unit 9…Display section

Claims

1. an ion detector for generating a current pulse signal in response to incident ions with a gain corresponding to a detector voltage; a voltage generating unit for applying a detector voltage to the ion detector; a branching unit for branching a voltage pulse signal based on a current pulse signal extracted from an anode of the ion detector into a plurality of signals; a pulse counting unit that detects one of the voltage pulse signals branched by the branching unit using a pulse count method and outputs a pulse count value; an analog detection unit that detects the other of the voltage pulse signals branched by the branch unit using an analog detection method and outputs an analog detection value; a conversion information storage unit that stores conversion information indicating a correspondence relationship between a predetermined pulse count value in a state where the pulse count value by the pulse count unit is not saturated under a detector voltage applied from the voltage generating unit to the ion detector during measurement and an analog detection value at that time; a converted count value calculation unit that, when either the pulse count value by the pulse count unit or the analog detection value by the analog detection unit obtained by measurement is greater than a predetermined value, calculates a converted count value as a detection value in place of the pulse count value by the pulse count unit, using the analog detection value at that time and the conversion information stored in the conversion information storage unit; A mass spectrometer comprising:

2. the conversion information storage unit holds a plurality of pieces of conversion information respectively corresponding to a plurality of different detector voltage values; 2. The mass spectrometer according to claim 1, wherein the converted count value calculation unit selectively acquires, from the conversion information storage unit, conversion information corresponding to one of the plurality of detector voltage values ​​applied from the voltage generation unit to the ion detector during measurement, and calculates the converted count value using the acquired conversion information.

3. a mode selection unit that displays a plurality of modes including a sensitivity priority mode and a dynamic range priority mode in a selectable manner and accepts a user's selection of the mode; the voltage generating unit has a function of changing a detector voltage to be applied to the ion detector in accordance with the mode selected by the mode selecting unit, and when the dynamic range priority mode is selected, applies a detector voltage of a lower value than when the sensitivity priority mode is selected; The mass spectrometer according to claim 2 , wherein the converted count value calculation unit calculates the converted count value by obtaining, from the conversion information storage unit, conversion information corresponding to a detector voltage according to the mode selected by the mode selection unit.

4. a saturation reference value storage unit that stores a saturation reference value associated with an analog detection value when saturation occurs in the output of the ion detector; 4. The mass spectrometer according to claim 1, wherein the voltage generating unit sets a detector voltage to be applied to the ion detector based on a pulse count value so that the analog detection value output from the analog detection unit does not exceed the saturation reference value.

5. a conversion information acquisition unit that, when a pulse count value by the pulse count unit is in a non-saturated state and both the pulse count value and a corresponding analog detection value are obtained, calculates conversion information using the pulse count value and the analog detection value and stores the conversion information in the conversion information storage unit; The mass spectrometer of claim 1 further comprising:

6. the conversion information acquisition unit calculates conversion information during measurement and stores the conversion information in the conversion information storage unit; 6. The mass spectrometer of claim 5, wherein when either the pulse count value by the pulse count unit or the analog detection value by the analog detection unit obtained by the measurement is greater than a predetermined value after the conversion information is stored in the conversion information storage unit during the execution of the measurement, the converted count value calculation unit outputs a converted count value calculated using the analog detection value at that time and the conversion information stored in the conversion information storage unit as a detection value in place of the pulse count value by the pulse count unit.

7. the conversion information acquisition unit calculates conversion information using the pulse count value and the analog detection value obtained in the measurement after the measurement is performed, and stores the conversion information in the conversion information storage unit; 6. The mass spectrometer of claim 5, wherein when either the pulse count value by the pulse count unit or the analog detection value by the analog detection unit obtained by measurement is greater than a predetermined value after the conversion information is stored in the conversion information storage unit, the converted count value calculation unit calculates the converted count value using the analog detection value at that time and the conversion information stored in the conversion information storage unit.

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