JP6727577B2 - Mass spectrometer and mass spectrometry method - Google Patents

Description

The present invention relates to a mass spectroscope and a mass spectrometric method for repeatedly performing a series of measurements of ion generation, acceleration to a mass separation section, and detection, and acquiring a mass spectrum based on an ion current signal output from a detector.

A time-of-flight mass spectrometer that acquires a mass spectrum of a measurement sample based on the time of flight of ions generated by applying energy to the measurement sample in an ion source reaches a detector is known as a prior art ( Patent Documents 1 and 2).

In the time-of-flight mass spectrometer disclosed in Patent Document 1, a detector detects ions emitted from an ion source and accelerated by an electric field generator. In time-of-flight mass spectrometry, ions having various mass-to-charge ratios (m/z ratios) arrive at a detector at different flight times as a series of a plurality of ion groups. As each group of ions reaches the detector, the detector produces an ion current signal in the form of an electrical pulse that is indicative of the time of flight and intensity of the ion. The timing of the electric pulse of this ion current signal can represent the time of flight of the ion, and the height of the electric pulse can be used to estimate the intensity of the ion flux.

The ion current signal generated by the detector is amplified by the preamplifier. The ion current signal amplified by the preamplifier is branched and supplied to a TDC (Time-to-Digital-Converter) and an analog addition module, which are arranged in parallel with each other. TDC acquires a mass spectrum in the mass range of trace ions. The analog summing module acquires mass spectra in the mass range where the amount of ions is high. The TDC and the analog addition module operate in synchronization with each other.

As described above, by arranging the TDC and the analog addition module in parallel, the dynamic range of the mass range of the measurement sample analyzed by the mass spectrometer can be expanded.

US Patent Application Publication No. 2011/0186727 (Published August 04, 2011) Japanese Patent Laid-Open No. 2008-59774 (Published March 13, 2008)

However, in the conventional technique as described above, the very weak ion current signal of the time-of-flight mass spectrometer is measured at high speed by the hardware such as the TDC and the analog addition module, so that it is very difficult to actually realize it. The problem is that it is not realistic.

For example, in the above-mentioned conventional technique, the ion current signal generated by the detector needs to be amplified by the preamplifier and branched to the TDC and the analog addition module. The pulse width of this ion current signal is extremely short, in nanosecond units, and it is necessary to handle very fast signal changes that rise and fall in nanosecond units. Therefore, the adjustment of the preamplifier is also delicate, complicated, and difficult.

Further, the accuracy of the measurement time of the ion current signal needs to be very high in picosecond units. For this reason, even if the cable length for physically branching and connecting the respective hardware is different from the assumed length of several centimeters, the mass analysis result is greatly affected. Therefore, the adjustment of the cable length is delicate, complicated, and difficult.

The present invention has been made in view of the above problems, and an object thereof is to provide a mass spectrometer and a mass spectrometry method that can easily realize expansion of the dynamic range of the mass range of a measurement sample. It is in.

In order to solve the above-mentioned problems, a mass spectrometer according to the present invention is an AD converter that AD-converts an ion current signal generated by a detector that detects ionized ions from a measurement sample, and the AD converter. And a data processor that generates a mass spectrum of the measurement sample based on the AD-converted ion current signal according to the above, and the data processor integrates the AD-converted ion current signal to obtain the mass spectrum. Performing an analog mode processing for generating the mass spectrum and a counting mode processing for generating the mass spectrum by counting the number of times the pulse height of the AD-converted ion current signal exceeds a predetermined threshold value. Is characterized by.

With this feature, an analog mode and a counting mode for expanding the dynamic range of the mass range of the measurement sample are implemented by software or a logic circuit. Therefore, there is no need for delicate, complicated, and difficult adjustment of hardware that handles a very weak ion current signal. As a result, the dynamic range of the mass range of the measurement sample can be easily expanded.

In the mass spectrometer according to the present invention, it is preferable that the data processor executes the analog mode processing and the counting mode processing by software or a logic circuit.

In the mass spectrometer according to the present invention, the AD converter is a high-speed digitizer that performs high-speed AD conversion on the ion current signal, and a sampling period of the high-speed digitizer is greater than a pulse interval of the ion current signal exceeding the threshold value. It is preferably short.

According to the above configuration, it is possible to reduce the dead time required until it becomes possible to detect the next pulse exceeding the threshold value after once detecting the pulse exceeding the threshold value of the ion current signal. ..

In the mass spectrometer according to the present invention, the sampling period of the high speed digitizer is preferably 1 nanosecond or less.

According to the above configuration, even when a small number of ions, two or several, are detected simultaneously within the mass resolution, the number of those ions can be accurately counted.

In the mass spectrometer according to the present invention, it is preferable that the analog mode processing and the counting mode processing operate simultaneously in parallel, or alternately operate in a time division manner.

According to the above configuration, it is possible to integrate spectra at high repetition frequencies.

In the mass spectrometer according to the present invention, the measurement sample includes a high-concentration component and a low-concentration component, the analog mode processing generates a mass spectrum of the high-concentration component, and the counting mode processing is the low-concentration component. It is preferable to generate a mass spectrum of the concentration component.

According to the above configuration, the mass spectrum of the high concentration component and the mass spectrum of the low concentration component can be measured at the same time with the same sample sample.

In the mass spectrometer according to the present invention, it is preferable that the measurement sample is air, the high concentration component is CO ₂ , and the low concentration component is N ₂ O.

According to the above configuration, mass spectra of CO ₂ and N ₂ O, which are closely related to soil microorganisms and plant life phenomena, can be measured at once with the same sample sample.

The mass spectrometer according to the present invention is preferably a time-of-flight mass spectrometer, a single collector magnetic field mass spectrometer, or a quadrupole mass spectrometer.

According to the above configuration, it is possible to calculate the flight time at which the ions reach the detector based on the generation time of the peak waveform of the ion current signal, and obtain the mass spectrum of the measurement sample.

It is preferable that the mass spectrometer according to the present invention further includes the detector that detects the ionized ions from the measurement sample.

A mass spectrometric method according to the present invention includes a signal generation step of detecting ionized ions from a measurement sample to generate an ion current signal, and an AD conversion step of AD-converting the ion current signal generated by the signal generation step. A data processing step of generating a mass spectrum of the measurement sample based on the ion current signal AD-converted by the AD conversion step, the data processing step integrating the AD-converted ion current signal. Thus, the analog mode step of generating the mass spectrum, and the counting mode of generating the mass spectrum by counting the number of times the pulse height of the AD-converted ion current signal exceeds a predetermined threshold value. And a process.

The present invention has an effect that the dynamic range of the mass range of the measurement sample can be easily expanded.

It is a block diagram which shows typically the structure of the mass spectrometer which concerns on embodiment. Is a graph showing the spectrum of the CO ₂ contained in the atmospheric components to be analyzed by the mass spectrometer. Is a graph showing the spectrum of the N _{2 O} contained in the atmospheric components, (a) is a graph showing a spectrum when only one of the N _{2 O} ions are detected, (b) the plurality of N ₂ It is a graph which shows a spectrum when O ion is detected. It is a graph which shows the ion current signal which the high-speed digitizer provided in the said mass spectrometer receives from a detector. (A) is a graph showing a mass spectrum generated by an analog mode processor provided in the mass spectrometer, and (b) is a graph showing a mass spectrum generated by a counting mode processor provided in the mass spectrometer. is there. (A) is a graph showing a mass spectrum of CO ₂ contained in the atmospheric component generated by the analog mode processor, (b) the N ₂ O contained in the atmosphere components generated by the counting mode processor It is a graph which shows the mass spectrum of. It is a graph showing the relationship between the concentration of CO ₂ contained in the area and the air component of the chromatogram obtained from the mass spectrum of the CO _2. Is a graph showing the relationship between the count value and the N _{2 O} concentration contained in the atmospheric components N _{2 O} ions contained in the counted above atmospheric components by the counting mode processor. (A) is a graph showing a Pb mass spectrum generated in the analog mode, and (b) is a graph showing a Pb mass spectrum generated in the counting mode. (A) is a graph showing the isotope ratios of ²⁰⁴ Pb and ²⁰⁶ Pb determined by the analog mode, and (b) is a graph showing the isotope ratios of ²⁰⁴ Pb and ²⁰⁶ Pb determined by the counting mode.

Hereinafter, embodiments of the present invention will be described in detail.

(Structure of the mass spectrometer 1 according to the present embodiment)
FIG. 1 is a block diagram schematically showing the configuration of the mass spectrometer 1 according to the embodiment. The time-of-flight mass spectrometer 1 includes a detector 2 for detecting ionized ions from a measurement sample 7 to generate an ion current signal, and a high-speed digitizer for high-speed AD conversion of the ion current signal generated by the detector 2. 3 and a data processing system 4 (data processor) that generates by software the mass spectrum of the measurement sample 7 based on the ion current signal that is AD-converted at high speed by the high-speed digitizer 3.

The data processing system 4 uses the analog mode processor 5 (analog mode processing) that generates the mass spectrum of the measurement sample 7 by software by integrating the ion current signals that have been AD-converted at high speed by the high speed digitizer 3 and the high speed digitizer 3. A counting mode processor 6 (counting mode processing) that generates the mass spectrum of the measurement sample 7 by software by counting the number of times the pulse height of the high-speed AD-converted ion current signal exceeds a predetermined threshold value. Have. The analog mode processor 5 and the counting mode processor 6 operate in parallel and simultaneously. The analog mode processor 5 and the counting mode processor 6 may alternately operate in a time division manner.

The sampling period of the high speed digitizer 3 is shorter than the pulse interval of the ion current signal exceeding a predetermined threshold value, and is preferably 1 nanosecond or less.

The measurement sample 7 contains a high concentration component and a low concentration component. The analog mode processor 5 generates a mass spectrum of the high concentration component contained in the measurement sample 7. The counting mode processor 6 generates a mass spectrum of the low concentration component contained in the measurement sample 7. For example, the measurement sample 7 is air, the high concentration component is CO ₂ , and the low concentration component is N ₂ O.

(How to obtain mass spectrum)
The mass spectrometer 1 repeats a series of measurements of ion generation, acceleration to the mass separation unit, and detection, and acquires a mass spectrum by integrating the ion current signal output from the detector 2.

The mass spectrum is acquired by setting the analog mode in which the ion current signal value is integrated by an AD converter (Analog-to-Digital Converter (ADC)) and the pulse height of the ion current signal. There are two methods, a counting mode and a counting mode.

The analog mode has the advantage that the amount of ions can be directly measured as the intensity of the ion current signal, but since the noise originating from the mass spectrometer is also integrated at the same time, the S/N (signal-to-noise) ratio is poor. However, it is difficult to measure a weak ion current signal.

On the other hand, in the counting mode, a high S/N ratio can be obtained by detecting the ion current signal exceeding the threshold value, but under the condition that a large number of ions fly in a short time interval, counting down of ions occurs and the mass spectrum is lost. Quantitatively deteriorates.

Therefore, it is necessary to use a different detection system for acquiring a mass spectrum, such as using an analog mode for measuring a large amount of abundant ions and a counting mode for measuring a small amount of ions.

However, it is very difficult to implement an analog mode detection system and a counting mode detection system in a time-of-flight or quadrupole mass spectrometer that acquires a mass spectrum with a single detector at a time. Yes, not realistic.

High-speed ADC accumulators (averagers) equipped with digital accumulator circuits such as field programmable gate arrays (FPGAs) have contributed to the expansion of the quantifiable range of time-of-flight mass spectrometers. However, the waveform integration in the analog mode by the averager may simultaneously dilute or mask the ion current signal of a substance existing at an extremely low concentration.

FIG. 2 is a graph showing the results of measurement without integrating the spectra of CO ₂ contained in the atmospheric components analyzed by the mass spectrometer 1. FIG. 3 is a graph showing the result of measurement without integrating the spectra of N ₂ O contained in the atmospheric component, and FIG. 3A is a graph showing the spectrum when only one N ₂ O ion is detected. And (b) is a graph showing a spectrum when a plurality of N ₂ O ions are detected. In the atmosphere, N ₂ O exists in an amount of about 1/1000 of CO ₂ .

As shown in FIG. 2, a relatively large amount and high concentration of CO ₂ ions have reached the detector, and a slight difference in flight energy (initial velocity) between individual CO ₂ ions is P1=6. It is observed as a peak waveform (Gaussian waveform) W1 having a half width of 2 nanoseconds (ns). This half width corresponds to a performance called mass resolution in the mass spectrometer.

On the other hand, in the case of N ₂ O shown in FIG. 3A, the peak waveform W2 is observed about 50 times out of 100 times of measurement, and the peak concentration W2 is not observed at the remaining 50 times at a low concentration. Is. In FIG. 3A, only one N ₂ O ion is detected in this measurement. Therefore, the pulse width is extremely narrow at P2=2.4 nanoseconds.

When the signals based on such a low concentration of N ₂ O are integrated in the analog mode described above, the detection probability of ions (peak waveform) is ½, so that the pulse (peak waveform) will be detected in the next measurement. Due to the phenomenon of not being observed or the peak waveform being detected at a slightly different flight time, the already obtained peak waveform is diluted by the random noise derived from the mass spectrometer. The result is a N ₂ O based signal strength decay.

In the counting mode described above, the ion current signal value is not integrated, and the peak waveform of the ion current signal detected for each measurement is counted. Absent.

In the counting mode, as shown in FIG. 2, when measuring a high-concentration sample in which a large amount of ions are detected in one measurement, counting of ions occurs, so that the quantitative determination result of ions cannot be obtained correctly. .. Therefore, by using the analog mode for quantification of a high-concentration sample, a result equivalent to the measurement result by the averager can be obtained.

The counting mode can also be implemented by the TDC that has been conventionally used in a time-of-flight mass spectrometer. However, once the TDC detects an ion, a dead time of about 15 nanoseconds is required until the next ion can be detected. Therefore, even when a plurality of ions of the same molecular species are detected within the mass resolution as shown in FIG. 3B, they correspond to the following ions other than the peak waveform W3 of the pulse width P3 corresponding to the first ion. There is a problem in that the peak waveform W4 having the pulse width P4 that cannot be detected cannot be detected, and in the TDC, there is a problem that the waveform integration (averaging) in the analog mode cannot be performed at the same time when the counting mode is performed.

(Operation of the mass spectrometer 1 according to the present embodiment)
First, the detector 2 detects ions generated by applying energy to the measurement sample 7. Then, the detector 2 generates an ion current signal based on the detected ions. Next, the high-speed digitizer 3 AD-converts the ion current signal detected by the detector 2 at a high sampling rate of 1 gigasample/second (GS/s) or more.

FIG. 4 is a graph showing the ion current signal that the high speed digitizer 3 receives from the detector 2. 5A is a graph showing a mass spectrum generated by the analog mode processor 5 provided in the data processing system 4, and FIG. 5B is a graph showing a mass spectrum generated by the counting mode processor 6 provided in the data processing system 4. It is a graph which shows. The horizontal axis represents the mass-to-charge ratio (m/z). The vertical axes of FIGS. 4 and 5(b) show the detection intensity represented by the ion current signal, and the vertical axes of FIG. 5(a) show the detection intensity represented by the ion count number.

The mass range R1 in which the peak waveform W5 shown in FIG. 4 occurs corresponds to the ions of the high-concentration component contained in the measurement sample 7. The mass range R2 in which the peak waveforms W6 and W7 that exceed the threshold Th are generated corresponds to the ions of the low concentration component contained in the measurement sample 7.

The peak waveform W5 of the ion current signal generated in the mass range R1 is integrated in the analog mode by the analog mode processor 5 to generate the mass spectrum shown in FIG. The peak waveforms W6 and W7 of the ion current signal exceeding the threshold Th generated in the mass range R2 are counted by the counting mode processor 6 in the counting mode, and the mass spectrum shown in FIG. 5B is generated.

By parallelizing the calculation processing in the analog mode by multithreading, it is possible to integrate spectra at high repetition frequencies.

(Effects of the embodiment)
In order to solve the above-mentioned problem, the mass spectrometer 1 according to the present embodiment performs waveform calculation in analog mode by the analog mode processor 5 on the waveform data of the ion current signal obtained from the high speed digitizer 3 for each measurement. And the ion counting process in the counting mode by the counting mode processor 6 are simultaneously performed in parallel.

The waveform calculation in the analog mode is performed in the mass range of a large amount of ions, and the counting in the counting mode is executed in the mass range of a very small amount of ions. Therefore, it is possible to acquire a mass spectrum having an ultra-high dynamic range, which cannot be obtained by a conventional mass spectrometer.

Conventionally, in a time-of-flight or quadrupole mass spectrometer that acquires a mass spectrum with a single detector, an analog mode suitable for measuring a large number of ions and a small amount of ions are detected. There was no choice but to choose one of the suitable counting modes. In the present embodiment, the two processing methods of the analog mode and the counting mode are implemented in the mass spectrometer 1 by the calculation processing of the data processing system 4 after acquiring the ion current signal. Therefore, the treatment method can be selected in any mass range. As a result, it becomes possible to acquire a highly quantitative mass spectrum having a very high dynamic range.

In addition, it is now possible to detect ions in the low-concentration region with a detection probability of less than 1 which could not be detected in the past, without impairing the conventional quantitative accuracy of the high-concentration component by the waveform calculation. The accuracy is significantly improved.

In the present embodiment, the counting mode processing is executed based on the ion current signal that has been AD-converted at high speed by the high-speed digitizer 3, so the dead time seen in TDC becomes the sampling rate of the high-speed digitizer 3. Therefore, the number of ions to be counted is reduced, and the quantitativeness of the mass spectrum is greatly improved. Typically, the conventional dead time of the order of 10 nanoseconds is shortened to 1 nanosecond or less in this embodiment. Therefore, even ions having the same mass-to-charge ratio can be simultaneously detected for ions having mass dispersion.

In this way, even when a small number of ions, such as two or a few ions, are detected simultaneously within the mass resolution, the number of those ions can be accurately counted. Therefore, even for low-concentration/medium-concentration samples, the corresponding ability (quantitativeness) is higher than that of TDC.

Furthermore, the conventional ion counting process requires a long measurement time, but this embodiment can correctly count several ions at a time, and can accurately count ions even at a high count rate. Therefore, information necessary for quantifying ions can be obtained in a shorter time than TDC, and the mass analysis time can be shortened.

This embodiment can be used for a detection system of a time-of-flight mass spectrometer. Further, like the time-of-flight mass spectrometer, the present invention can be applied to a quadrupole mass spectrometer that acquires a mass spectrum with a single detector, and a single collector magnetic field mass spectrometer.

In this embodiment, an example in which the analog mode and the counting mode are implemented by the software of the data processing system 4 has been shown. However, the present invention is not limited to this. Instead of the data processing system 4, a logic circuit such as an FPGA (Field Programmable Gate Array) or an application-specific integrated circuit (ASIC) implements the analog mode and the counting mode by hardware. May be.

The mass spectrometer according to this embodiment can be used for, for example, quantifying a metabolic compound of a drug in the body by mass spectrometry.

Drugs are absorbed by the body, distributed in various tissues, and then metabolized (mainly in the liver) and excreted. Universal safety is required in the course of the pharmaceutical process. In particular, measurement of structural changes in metabolic processes, and measurement of changes in metabolic pathways and rates due to coexistence with other drugs are extremely important for ensuring the safety of drugs. For such measurement, it is necessary to find a drug-derived compound from various compounds that normally exist in the living body and perform quantification.

Conventionally, an LC (liquid chromatography)-triple quadrupole mass spectrometer is widely used for these measurements. However, in principle, the LC-triple quadrupole mass spectrometer cannot measure a plurality of eluting substances that are close to each other on the LC at one time. Although the time-of-flight mass spectrometer does not have this problem, the conventional time-of-flight mass spectrometer does not have a sufficient quantitative dynamic range for measurement. INDUSTRIAL APPLICABILITY The present invention exerts a remarkable effect in identifying and quantifying the components in such a complex and highly diverse sample.

Similar problems apply not only to humans and livestock such as pharmaceuticals, but also to plant fields such as pesticides (http://tominet.jp/yakuji/webfile/t1_11b3237e6da70060cdf96a1e1168533c.pdf (see pharmacokinetic analysis and Pk/Pd)) ).

In recent years, as pointed out by the United States Environmental Protection Agency (EPA), pharmaceutical products discarded from households are released into the environment, and compounds metabolized by forests, rivers, marine organisms, and microorganisms are complicatedly released into the environment. It is feared that it will be affected. The present invention is believed to be able to provide a method for solving problems in fields where simultaneous quantification of these various compounds over a wide range is required (https://www.epa.gov/hwgenerators/frequent- questions-about-management-standards-hazardous-waste-pharmaceuticals-proposed).

An embodiment of the present invention will be described below with reference to FIGS. 6 to 8.

(Method of Example 1)
Atmospheric components, particularly CO ₂ and N ₂ O, are deeply involved in life phenomena of soil microorganisms and plants. Therefore, detailed tracking of changes in the amounts of CO ₂ and N ₂ O, which are atmospheric components, is significant in monitoring applied air pollution caused by excessive administration of chemical fertilizers, including applied research in agriculture.

However, the abundance ratio of these CO ₂ and N ₂ O compounds in the atmosphere is about 1000:1. Therefore, conventionally, it has been difficult to measure the mass of the same sample sample at one time.

Therefore, as an example of the present embodiment, a small amount of N ₂ O is adjusted using gas chromatography (GC) so that it can be quantified in a counting mode, and 1000 times the amount of N ₂ O exists. An attempt was made to quantify CO ₂ in analog mode.

As the detector 2 for mass spectrometry, a small multi-orbiting time-of-flight mass spectrometer InfiTOF-UHV (MSI.Tokyo Co., Ltd.) was used, and a U5303A high-speed digitizer (Keysight, USA) was used as the high-speed digitizer 3. The connection was performed and the mass measurement was performed. For separation of atmospheric components as the measurement sample 7, a 0.32 mmID x 15 mL GS-CARBONPLOT column (Agilent, USA) was used and 2.0 mL/min helium was used as a carrier.

Mass measurement was performed at 1 millisecond (ms) intervals, and the spectrum of the obtained ion current signal was captured by a personal computer (PC) equipped with two XEON (Intel Corporation) processors. Then, in 16 parallel object-type parallel processes, ion counting in the counting mode and integration of the waveform of the ion current signal in the analog mode were simultaneously executed. Next, the mass spectrum was recorded as a histogram based on the integrated waveform in the analog mode and the counting mode for each time resolution (for example, 100 milliseconds (ms)) designated in advance by the user.

(Results of Example 1)
The mass difference between CO ₂ and N ₂ O is only 11.3 millidaltons (mDa), but the experiment was carried out under the condition that the mass spectrometer (mass resolution 13,000) used was able to completely separate them. went. A fixed loop was used to inject into a 50 microliter (μL) air separation column at 1 minute intervals to obtain a chromatogram.

CO ₂ and N ₂ O were eluted at a retention time of 0.53 minutes and a retention time of 0.65 minutes, respectively, and the pulse width of each was about 2 seconds. The average peak intensity during a single ion response of CO ₂ and N ₂ O under these conditions was approximately −60 millivolts (mV) and the baseline noise level was 0.5 mV. Therefore, the detection threshold of ion counting was set to -20 mV. Further, the pulse width of the N ₂ O single ion response is about 2 nanoseconds (ns), and the detection width (corresponding to mass resolution) of the N ₂ O single ion peak under the experimental conditions is 9.8 nanoseconds (ns). )Met.

For every 100 measurements, the CO ₂ chromatogram is obtained from the waveform integration in the analog mode, the N ₂ O chromatogram is obtained from the histogram based on the counting mode, and the CO ₂ and N ₂ O are obtained from those chromatogram areas. It was decided to quantify with. A standard dilution series was prepared by diluting CO ₂ and N ₂ O with nitrogen gas, and the response was confirmed by measuring the standard dilution series.

FIG. 6 shows a waveform in the analog mode and a histogram in the counting mode, which were simultaneously measured by this example. FIG. 6A is a graph showing a mass spectrum of CO ₂ produced in the analog mode, and FIG. 6B is a graph showing a mass spectrum of N ₂ O produced in the counting mode.

CO ₂ having a relatively high concentration is quantified by the analog mode using the area (integral value) in the pulse width P3 of the peak waveform W8 shown in FIG. The small amount of N ₂ O is quantified by the counting mode based on the total count value in the pulse width P4 of the histogram W9 shown in FIG. 6B.

FIG. 7 is a graph showing the relationship between the area of the chromatogram obtained from the mass spectrum of CO ₂ based on the average data in the analog mode and the concentration of CO ₂ contained in the atmospheric component of the measurement sample 7. The horizontal axis represents the CO ₂ concentration, and the vertical axis represents the area of the CO ₂ chromatogram. As shown in FIG. 7, good linear response was confirmed in the quantitative results of CO ₂ mass spectrometry in the concentration range of 400 ppm to 8000 ppm.

FIG. 8 is a graph showing the relationship between the count value of N ₂ O ions counted in the counting mode and the concentration of N ₂ O contained in the atmospheric components of the measurement sample 7. The horizontal axis represents the concentration of N ₂ O, and the vertical axis represents the count value of N ₂ O ions. Since the pulse width of the chromatogram is 2 seconds (measured 2000 times), the upper limit of measurement (the level at which one or more ions can be reliably detected per measurement) is predicted at about 1000 counts. As shown in FIG. 8, a good linear response of the count value up to 2000 counts of the count value of N ₂ O ions is shown.

Another embodiment of the present invention will be described below with reference to FIGS. 9 and 10.

(Method of Example 2)
In clarifying the history of the solar system, the history of the earth, and the history of life, the formation of uranium and lead from isotopic ratios of meteorites and rocks using radiative decay from uranium (U) to lead (Pb) U-Pb dating, which determines the age, has made a great contribution.

Conventionally, in this U-Pb age analysis, a secondary ion mass spectrometer (SIMS) that mass-analyzes secondary ions generated by irradiating a sample with an ion beam focused to a diameter of several tens of μm is widely used. Has been used.

However, the secondary ion mass spectrometer has a weak point that the ionization efficiency is low, and thus the obtained spatial resolution and statistical accuracy are limited.

Therefore, as an example of the present invention, an attempt was made to improve the detection sensitivity in the secondary ion mass spectrometer, that is, the statistical accuracy, by using the counting mode.

In the experiment, a lead plate was used as a sample, and this was measured with a multi-turn time-of-flight secondary ion mass spectrometer MULTUM-SIMS (Ref. M. Ishihara et al., Surface Interface Anal., 42, 1598 (2010)). did. The measurement was performed at 2 ms intervals, and the obtained spectra were loaded into a PC equipped with two XEON (Intel, USA) processors, and ion counting and waveform integration were performed simultaneously in 16 parallel target-type parallel processes. ..

(Results of Example 2)
FIG. 9A is a graph showing the Pb mass spectrum generated in the analog mode, and FIG. 9B is a graph showing the Pb mass spectrum generated in the counting mode.

The mass spectra of stable isotopes of lead, ²⁰⁴ Pb, ²⁰⁶ Pb, ²⁰⁷ Pb, and ²⁰⁸ Pb, obtained from the integration of the waveforms in the analog mode and the histogram based on the counting mode, are shown in FIGS. 9(a) and (b). .. The natural abundance ratios of lead isotopes originating from the earth are 1.4%, 24.1%, 22.1%, and 52.4% for ²⁰⁴ Pb, ²⁰⁶ Pb, ²⁰⁷ Pb, and ²⁰⁸ Pb, respectively.

The experiment was performed under conditions suitable for the counting mode in which ²⁰⁸ Pb ions, which have the highest abundance, were detected several times in one ion beam irradiation, and the mass spectrum was obtained by integrating the ion current signals for 10,000 ion beam irradiations. Obtained.

It can be seen that in the spectrum acquired in the analog mode shown in FIG. 9A, the peak of ²⁰⁴ Pb whose presence cannot be determined due to noise is clearly detected in the counting mode shown in FIG. 9B.

FIG. 10A is a graph showing the isotope ratios of ²⁰⁴ Pb and ²⁰⁶ Pb determined by the analog mode, and FIG. 10B is a graph showing the isotope ratios of ²⁰⁴ Pb and ²⁰⁶ Pb determined by the counting mode. is there.

The same measurement was performed 10 times, and the isotope ratios of ²⁰⁴ Pb and ²⁰⁶ Pb in each measurement are shown in FIG. 10. For spectra acquired in analog mode, quantification is performed using the area (integral value) in the pulse width of each peak waveform, and for spectra acquired in counting mode, quantification is performed based on the total count value in the same pulse width as analog mode. went. The horizontal axis represents the number of measurements and the vertical axis represents the ²⁰⁴ Pb/ ²⁰⁶ Pb ratio. The broken line L1 indicates the natural abundance ratio of ²⁰⁴ Pb and ²⁰⁶ Pb (1.4/24.1=0.58). It can be seen that the counting mode is superior to the analog mode in quantitativeness in terms of both the error from the natural abundance ratio in all 10 measurements and the statistical accuracy (error bar) at each measurement point.

[Example of software implementation]
The data processing system 4 of the mass spectrometer 1 may be realized by a logic circuit (hardware) formed in an integrated circuit (IC chip) or the like, or by software using a CPU (Central Processing Unit). Good.

In the latter case, the data processing system 4 includes a CPU that executes instructions of a program that is software that realizes each function, a ROM (Read Only Memory) in which the program and various data are recorded so that they can be read by a computer (or CPU). Further, it is provided with a storage device (these are referred to as “recording medium”), a RAM (Random Access Memory) for expanding the program, and the like. Then, the computer (or CPU) reads the program from the recording medium and executes the program to achieve the object of the present invention. As the recording medium, a "non-transitory tangible medium", for example, a tape, a disk, a card, a semiconductor memory, a programmable logic circuit, or the like can be used. The program may be supplied to the computer via any transmission medium (communication network, broadcast wave, etc.) capable of transmitting the program. The present invention can also be realized in the form of a data signal embedded in a carrier wave, in which the above program is embodied by electronic transmission.

The present invention is not limited to the above-described embodiments, but various modifications can be made within the scope of the claims, and embodiments obtained by appropriately combining the technical means disclosed in the different embodiments Is also included in the technical scope of the present invention.

1 mass spectrometer 2 detector 3 high-speed digitizer 4 data processing system (data processor)
5 Analog Mode Processor (Analog Mode Processing)
6 Counting mode processor (counting mode processing)
7 Measurement sample

Claims (9)

An AD converter that AD-converts an ion current signal generated by a detector that detects ionized ions from the measurement sample;
A data processor that generates a mass spectrum of the measurement sample based on the ion current signal AD-converted by the AD converter,
Analog mode processing in which the data processor integrates the AD-converted ion current signals to generate the mass spectrum;
Counting the number of times the pulse height of the AD-converted ion current signal exceeds a predetermined threshold value to perform counting mode processing for generating the mass spectrum ,
The measurement sample contains a high concentration component and a low concentration component,
The ion current signal includes a high concentration component ion current signal corresponding to the high concentration component and a low concentration component ion current signal corresponding to the low concentration component,
The analog mode processing generates a mass spectrum of the high concentration component by integrating the high concentration component ion current signal,
The counting mode processing is characterized by generating a mass spectrum of the low-concentration component by counting the number of times that the pulse height of the low-concentration component ion current signal exceeds the predetermined threshold value. apparatus. The mass spectrometer according to claim 1, wherein the data processor executes the analog mode processing and the counting mode processing by software or a logic circuit. The AD converter is a high-speed digitizer that performs high-speed AD conversion of the ion current signal,
The mass spectrometer according to claim 1, wherein the sampling period of the high-speed digitizer is shorter than the pulse interval of the ion current signal exceeding the threshold value. The mass spectrometer according to claim 3, wherein the sampling period of the high-speed digitizer is 1 nanosecond or less. The mass spectrometer according to claim 1 or 2, wherein the analog mode processing and the counting mode processing operate simultaneously in parallel or alternately in a time division manner. The measurement sample is the atmosphere,
The high concentration component is CO _Two And
The low concentration component is N _Two The mass spectrometer according to any one of claims 1 to 5, which is O. The mass spectrometer according to claim 1, wherein the mass spectrometer is a time-of-flight mass spectrometer, a single-collector magnetic field mass spectrometer, or a quadrupole mass spectrometer. The mass spectrometer according to claim 1, further comprising the detector configured to detect ionized ions from the measurement sample. A signal generation step of detecting ionized ions from a measurement sample containing a high concentration component and a low concentration component to generate an ion current signal,
AD conversion step of AD-converting the ion current signal generated by the signal generation step into a high concentration component ion current signal corresponding to the high concentration component and a low concentration component ion current signal corresponding to the low concentration component When,
Data processing for generating a mass spectrum of the measurement sample based on the high concentration component ion current signal corresponding to the high concentration component and the low concentration component ion current signal corresponding to the low concentration component which are AD-converted in the AD conversion step Including steps and
An analog mode step in which the data processing step generates a mass spectrum of the high-concentration component by integrating the AD-converted high-concentration component ion current signal;
A counting mode step of generating a mass spectrum of the low-concentration component by counting the number of times that the pulse height of the AD-converted low-concentration component ion current signal exceeds a predetermined threshold value. Mass spectrometry method.

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