WO2015102053A1

WO2015102053A1 - Mass spectrometer

Info

Publication number: WO2015102053A1
Application number: PCT/JP2014/050032
Authority: WO
Inventors: 学上田
Original assignee: 株式会社島津製作所
Priority date: 2014-01-06
Filing date: 2014-01-06
Publication date: 2015-07-09
Also published as: JP6149947B2; JPWO2015102053A1

Abstract

In the present invention, an operator measures each of a plurality of prepared samples by setting each sample in order in a measurement position (sample (25) position) in an ionization region (20). A real-time chromatogram creation unit (41) creates a chromatogram on the basis of sequentially obtained data from a main mass spectrometer unit and displays the chromatogram on the screen of a display unit (61). Further, during measurement, the operator inputs sample information about each sample from an input unit (60) and inputs measurement time information on the basis of the starting point and ending point of a peak that appears on the displayed chromatogram. A comment input reception unit (42) stores the sample information and measurement time information input in this way in a data file that the measurement data is stored in and saves the information in a storage unit (44). As a result, because the measurement data, the sample information for each sample, and the measurement time information are associated, it is possible to display sample information at an appropriate position when displaying a chromatogram or mass spectrum.

Description

Mass spectrometer

The present invention relates to a mass spectrometer, and more particularly, to a mass spectrometer using an ionization method capable of in-situ analysis in real time.

Various ionization methods are known as a method for ionizing sample components in a mass spectrometer. These ionization methods can be broadly divided into a method of performing ionization under a vacuum atmosphere and a method of performing ionization under a substantially atmospheric pressure atmosphere. The latter is generally referred to as an atmospheric pressure ionization method (API = Atmospheric Pressure Ionization). Is done. The atmospheric pressure ionization method is advantageous in that it is not necessary to evacuate the ionization chamber, and a sample that is difficult to handle in a vacuum atmosphere, such as a liquid sample or a sample containing a lot of moisture, can be easily ionized.

Well-known atmospheric pressure ionization methods include electrospray ionization (ESI = ElectroSpray Ionization) and atmospheric pressure chemical ionization (APCI = Atmospheric Pressure Chemical Ionization) used in liquid chromatograph mass spectrometers. However, in recent years, new atmospheric pressure ionization methods have been developed or proposed one after another and attracting attention.

Many of these new atmospheric pressure ionization methods were developed in response to the need to easily analyze the substances present in our immediate surroundings (Ambient), and these ionization methods are based on ambient ionization (Ambient Ionization). The mass spectrometry using these ionization methods is called ambient mass spectrometry (Ambient Mass Spectrometry) (see Non-Patent Documents 1 to 3, etc.). Although it is difficult to precisely define the ambient ionization method, the basic concept is that in-situ measurement is possible in real time without special sample preparation or pretreatment. You can say that.

Typical ambient ionization methods include a real-time direct analysis (DART = Direct Analysis Real Time) method, a desorption electrospray ionization (DESI = Desorption ElectroSpray Ionization) method and the like. As shown, probe electrospray ionization (PESI = Probe ElectroSpray Ionization) method, electrospray assisted / laser desorption ionization (ELDI = Electrospray assisted Laser Desorption Ionization) method, atmospheric pressure solid analysis probe (ASAP = Atmospheric Solids Analysis Probe) A variety of ionization methods such as the method are included in the ambient ionization method.

For example, in the DART method, it is possible to ionize components in a sample simply by holding a solid or liquid sample over a spray flow of excited water molecules mixed with heated gas (Non-patent Document 4). Etc.) On the other hand, in the DESI method, ionization of components in a sample can be performed by spraying a microdroplet of a charged solvent onto the sample. Therefore, these ionization methods do not require special sample preparation for ionization, the structure of the ion source is simple and advantageous in terms of cost, and it is inert to supply from the outside for ionization. Since there is only a gas, there is an advantage that handling is easy and liquid such as a solvent is not sprayed on the sample, so that the sample after analysis is easy to handle.
Hereinafter, a mass spectrometer using an ion source based on the DART method which is a typical ambient ionization method (hereinafter referred to as a DART mass spectrometer) will be described as an example.

An example of a typical measurement procedure when performing measurements on a large number of samples using a DART mass spectrometer will be described with reference to the flowchart shown in FIG.
First, measurement (blank measurement) is performed for a certain period of time in a state where nothing is set at a measurement position (position where a spray flow of excited water molecules is sprayed in a DART ion source) (step S81). In this blank measurement and subsequent sample measurement, in order to detect unknown components, scan measurement over a predetermined mass-to-charge ratio range is repeatedly performed, and data representing a mass spectrum in the mass-to-charge ratio range is collected for each scan measurement. . The data processing unit in the DART mass spectrometer integrates the signal intensity obtained for each scan measurement over the entire mass-to-charge ratio range, and plots this over time, so that the total ion chromatogram can be obtained in real time. Create with.

FIG. 5 is an example of a chromatogram (total ion chromatogram) created and displayed in real time. During the blank measurement period, background noise due to various factors appears on the chromatogram.

After completion of the blank measurement for a predetermined time, the worker (user) performs measurement on the sample by setting one of the samples at the measurement position (step S82). When the sample is set at the measurement position, peaks corresponding to one or more components included in the sample appear on the chromatogram as shown in FIG. Therefore, the operator must specify the information that identifies the sample, such as the name of the measured sample, and the time at which the sample was detected (start time and end time of the peak appearing in the chromatogram) on paper or a personal computer (PC). Are recorded in a document or table (step S83). Then, steps S82 and S83 are repeated until the measurement for all the samples is finished (No is determined in step S84).

After the measurement of a large number of samples prepared in advance in this way, the worker performs analysis in the following procedure. FIG. 16 is a flowchart showing an example of this analysis procedure.
The operator confirms the sample information recorded on the paper or the like at the time of measurement and the detection time (step S91), and the mass spectrum obtained in the time range in which one sample is detected (usually the peak top on the chromatogram). The mass spectrum corresponding to is selected, and the mass spectrum obtained in the blank measurement time range is subtracted from the mass spectrum. As a result, a mass spectrum from which the background due to various factors has been removed is obtained (step S92).

Next, based on the mass-to-charge ratio corresponding to the peak appearing in the mass spectrum after background removal, the worker specifies the type of compound and the structural formula of the compound contained in the sample (step S93). In general, a peak having a large signal intensity appearing in a mass spectrum may be regarded as a molecular ion peak of a compound, and a compound or a structural formula may be specified. However, depending on the type of the compound, an Na addition ion, NH since the adduct ion peak such as ₃ additional ions appear with high signal strength, it may be necessary to perform such adduct ion peak even considering compound or structure determination.

The worker enters comment information such as the specified compound name and structural formula at an appropriate position on the mass spectrum (in the vicinity of the peak used for specifying the compound, etc.). At this time, if comment information cannot be entered near the target peak, such as when the signal strength is low or the peak interval is narrow, draw an enlarged view of the mass spectrum and enter the comment information there. To do. If the operations of steps S91 to S94 are completed for all the measured samples (determined as Yes in step S95), the process proceeds to step S96.

Once the mass spectra describing the compound information, etc. for each sample are obtained, the operator compares the mass spectra with each other to determine the difference in peak mass-to-charge ratio and the peak signal intensity at the same mass-to-charge ratio. Check for differences and calculate the amount of the difference if necessary. For example, when one sample is a normal sample and the other sample is a normal / abnormal evaluation target sample, the difference from the mass spectrum for the normal sample may be obtained. Thus, a table or graph showing the difference between the mass-to-charge ratio and the difference in signal intensity is created and displayed together with the extracted ion chromatogram or mass spectrum at the target mass-to-charge ratio (steps S96 and S97). .
Through the analysis work as described above, it is possible to obtain information indicating a difference or commonality among a plurality of samples.

As described above, in a mass spectrometer equipped with a DART ion source or the like, measurement can be easily performed by simply holding the sample over the measurement position. There is.
(1) Selection of a sample to be measured, timing for setting the sample at a measurement position, etc. are left to the measurer, and measurement is very easy and flexible in that respect. On the other hand, the operator must record the sample name, detection time, etc. on paper, etc., and it is necessary to proceed with the work by referring to the record at the time of analysis. Losing the recorded information will greatly hinder the analysis work, so it is necessary to manage such information properly so that it can be quickly retrieved as needed. However, such management is very troublesome and cumbersome. .

(2) At the time of analysis, it is necessary to manually subtract the mass spectrum obtained in the blank measurement time range from the mass spectrum obtained at the detection time of each sample, which is very cumbersome and prone to errors.
(3) It is necessary for the operator to manually calculate the difference between the mass-to-charge ratio and the signal intensity based on the mass spectrum of each sample and judge the result. For this reason, not only does the work take time, but the judgment tends to vary due to differences in the skill and experience of the operator.
(4) When writing comment information such as a specified compound name on the mass spectrum, the operator determines whether writing is difficult because the signal intensity of the peak to which the information is to be associated is low or the peak interval is narrow. Therefore, it is necessary to perform an operation for displaying an enlarged view of the mass spectrum as necessary. Such work is cumbersome, and variations in the manner of mass spectrum display are likely to occur among workers.
(5) When specifying a compound or structural formula from the mass-to-charge ratio of peaks on a mass spectrum, it may be necessary to determine peaks other than molecular ions such as adduct ions. This is not possible unless the worker is loaded with a worker, and an inexperienced worker may miss such a special ion peak. As a result, an accurate analysis result may not be obtained.

The present invention has been made in view of the problems as described above, and its main purpose is to enable easy and easy measurement while reducing the burden on the operator, improving the efficiency of measurement and analysis, It is an object of the present invention to provide a mass spectrometer capable of reducing the variation in results depending on the level of skill and experience.

The present invention made to solve the above problems is a mass spectrometer that performs measurement in real time on a sample placed at a predetermined measurement position that is an atmospheric pressure atmosphere,
a) a comment input receiving unit that receives input of comment information including at least sample information for specifying a sample to be measured by a user during measurement execution;
b) The comment information received by the comment input receiving unit is stored in a data file in which measurement data collected at the time of the reception is stored, or in another file associated with the data file. A data storage unit to store;
It is characterized by having.

The mass spectrometer according to the present invention can be a mass spectrometer using various ion methods called ambient ionization methods such as the DART method, DESI method, PESI method, ELDI method, and ASAP method described above.

In a mass spectrometer equipped with such an ionization ion source, an operator (user) appropriately selects a sample from a plurality of samples prepared in advance and sets the sample at a predetermined measurement position to execute measurement on the sample. can do. Therefore, in the mass spectrometer according to the present invention, the comment input reception unit displays, for example, a screen on which a comment input field for an operator to input comment information is displayed on a display unit such as a display monitor during measurement. The information input in the input field is accepted.

The operator may input text by keyboard operation or the like, but may input by selection by the operator from a list (for example, pull-down menu) in which a plurality of pre-registered information is listed. . That is, the comment input receiving unit may be configured to receive sample information selected by an operator from a list in which a plurality of sample information is registered in advance as one of the comment information. In addition, appropriate information may be input from such a list by moving it to a predetermined column by an operation such as drag and drop. The format and method of such input are not particularly limited in the present invention.

When acceptance by the comment input acceptance unit is confirmed, the data storage unit stores the accepted comment information in a data file in which measurement data collected at the time of acceptance is stored. Alternatively, it is stored in another file associated with the data file. However, the comment information may be stored in the data file or the other file even during the measurement execution or after the measurement is completed. That is, when a plurality of samples are measured in sequence, each time the comment information for each sample is input, it may be stored in a file, or the comment information input for each sample may be temporarily stored. It is also possible to store the comment information stored in a file after all the samples have been measured.

In the mass spectrometer according to the present invention, as long as sample information on a sample appropriately selected by an operator at the time of measurement is appropriately input, measurement data and sample information for the sample are automatically associated and stored. . Therefore, sample information can be automatically obtained during the analysis based on the measurement data without depending on confirmation or judgment by the operator.

Further, in the mass spectrometer according to the present invention, the comment input receiving unit may start time (zero time) from the start time of a series of measurements in addition to sample information such as a sample name. The start time and end time of the period when the measurement for the sample is performed can be received as one of the comment information.

Specifically, the mass spectrometer according to the present invention further includes a measurement-time chromatogram display processing unit that creates a chromatogram based on measurement data in real time and renders it on a display screen, and the comment input reception unit includes a display screen. It is preferable that the time corresponding to the position indicated by the operator in the chromatogram drawn above is received as the time information.

In this configuration, for example, the operator instructs the start point and the end point of the peak appearing in the displayed chromatogram by a click operation with a pointing device. Then, the comment input receiving unit recognizes the time corresponding to the clicked position, and acquires it as the time information of the measurement of the sample corresponding to the peak. Of course, the operator may read the peak start time and end time and input them as text, but the operation is simplified by designating the time only by clicking as described above.

The sample information is preferably input based on the judgment of the operator, but the measurement time information may be automatically collected without involving the operator.
Therefore, the mass spectrometer according to the present invention further includes a measurement time chromatogram creation unit that creates a chromatogram in real time based on measurement data, and a peak detection unit that detects a peak in the chromatogram,
The data storage unit uses the time information obtained from the detection result by the peak detection unit as measurement time information for the sample, along with the comment information received by the comment input reception unit, in the data file or another data file associated with the data file. The file may be stored in the file.

Here, the peak detection method in the peak detection unit may be a known various method, that is, a method using a gradient of a chromatogram curve, a peak height, a peak width, or the like. According to this configuration, since the operator does not need to input the measurement time information, the work load on the operator can be reduced, and an erroneous time can be prevented from being input. In order to avoid erroneously recognizing a noise peak due to disturbance or the like as a peak derived from a sample, for example, a peak non-detection period so that a peak is not detected for a predetermined time after detecting one peak. Alternatively, a peak detection window for detecting a peak may be provided.

In the mass spectrometer according to the present invention, the comment information received by the comment input receiving unit, particularly the sample information, is created on the basis of the data obtained by the measurement and displayed on the display screen on the chromatogram or mass spectrum. It is advisable to display at an appropriate position.

For example, as described above, when a chromatogram is created and displayed in real time based on measurement data, sample information corresponding to the peak may be displayed in the vicinity of the peak appearing in the chromatogram. At this time, the position where the comment information such as the sample information is displayed may be automatically determined according to a predetermined algorithm, or the display position may be designated by the operator. For example, when inputting comment information, the operator may be allowed to specify the position where the comment information is displayed on the chromatogram or mass spectrum.

In the mass spectrometer according to the present invention, a preferred first aspect is
A spectrum subtracting unit that subtracts a mass spectrum obtained by blank measurement without a sample from a mass spectrum obtained by measurement in a state where the sample is present, identified based on the comment information received by the comment input acceptance unit; ,
A mass spectrum display processing unit for displaying the mass spectrum subtracted by the spectrum subtraction unit;
Is further provided.

In this first aspect, the spectrum subtraction unit determines whether there is no sample (blank state) or a sample based on, for example, sample information which is one of the comment information, and uses the measurement time information. The time range in which the measurement result of each state is obtained is determined. Then, the subtracted mass spectrum is obtained by subtracting the signal intensity value of each mass-to-charge ratio for the two mass spectra obtained in the respective time ranges. Since the mass spectrum obtained in the absence of the sample can be regarded as background due to noise or the like, this subtraction processing corresponds to processing for removing the background. As a result, the mass spectrum from which the background has been removed can be automatically obtained for each sample without the operator determining the target mass spectrum or performing a subtraction operation.

In the first aspect, the mass spectrum display processing unit may display at least a part of the comment information received by the comment input receiving unit on the subtracted mass spectrum.

Moreover, the preferable 2nd aspect in the mass spectrometer which concerns on this invention is a said 1st aspect,
A difference information extraction unit for extracting information on the difference between the subtracted mass-mass spectra respectively obtained for two or more different samples;
A difference information display unit for displaying the difference information extracted by the difference information extraction unit;
Is further provided.

The difference information here is a difference in peak signal intensity at the same mass-to-charge ratio, a difference in peak mass-to-charge ratio indicating the maximum signal intensity, and the like. What information is extracted as the difference information for the two mass spectra, what conditions are considered to be different may be set in advance. Further, the display of the difference information may be a display that can identify, for example, only a peak related to the difference on the mass spectrum or a part thereof, for example, only a peak part having a different signal intensity. Specifically, it is conceivable that a peak or a part of a peak related to a difference is displayed in a different display color from other peaks or peak parts, or a specific mark is attached to a peak related to a difference. Further, instead of the peak related to the difference, the display color of the mass-to-charge ratio corresponding to the peak may be changed or a mark may be attached.

According to the second aspect, the operator compares the mass-to-charge ratios and signal intensities of the peaks on the two mass spectra, calculates the difference amount, and determines whether the difference is significant. There is no need to In addition, the operator can easily grasp the peak determined to have a difference.

Furthermore, a preferable third aspect of the mass spectrometer according to the present invention is the above first aspect.
A compound information storage unit for storing compound information in which the type of compound and mass-to-charge ratio information are associated;
A compound specifying unit for specifying a compound and / or chemical structural formula by comparing the mass-to-charge ratio of the peak on the mass spectrum with the compound information stored in the compound information storage unit;
A compound information display unit for displaying information indicating the compound and / or chemical structural formula specified by the compound specifying unit in association with a peak and / or mass spectrum on a chromatogram;
Is further provided.

The above compound information can be obtained from various compound databases that are generally available. In addition, a database created by the operator himself based on the results of actually measuring various compounds can also be used. In addition, the mass-to-charge ratio information registered in the compound information is generally the mass-to-charge ratio information of molecular ions, but compounds that easily generate adduct ions added by specific substances or ions desorbed from specific parts. For this, it is preferable to register mass-to-charge ratio information of various molecular-related ions other than molecular ions.

According to the third aspect, accurate compound information can be automatically acquired without the operator himself / herself performing complicated work for specifying the compound contained in the sample and its chemical structural formula. . When a single compound or chemical structural formula cannot be specified, a plurality of candidates may be extracted, and the operator may make a final decision by listing these candidates.

According to the mass spectrometer of the present invention, the comment information including the sample information is stored in the data file in which the measurement data is stored or the file associated with the data file. It becomes easy and traceability is ensured. In addition, when analyzing data collected by measurement, important information for analysis such as sample name and measurement time of each sample can be extracted immediately, so even if the analysis is performed automatically, the operator will do it manually Even in this case, the efficiency of analysis can be improved.

Further, according to the first aspect of the mass spectrometer according to the present invention, the labor of manually subtracting the mass spectrum of the blank measurement from the mass spectrum of each sample becomes unnecessary, and the analysis work is efficiently performed. This can be done and work errors can be reduced.

Further, according to the second aspect of the mass spectrometer according to the present invention, the operator can manually compare the mass-to-charge ratio and signal intensity of the peaks on the two mass spectra, calculate the difference amount, There is no need to determine whether or not the difference is significant. Thereby, the analysis work can be performed efficiently, and variations in results due to differences in the skill and experience of the worker do not occur, and an accurate difference analysis can be performed.

Further, according to the third aspect of the mass spectrometer of the present invention, it is not necessary for the operator to specify the compound or chemical structural formula, and the efficiency of the analysis work can be further improved. In addition, it is possible to accurately specify a compound or chemical structural formula without depending on the skill and experience of the operator.

The block diagram of the principal part of the DART mass spectrometer which is 1st Example of this invention. The flowchart which shows an example of the measurement procedure and operation | movement at the time of performing the measurement with respect to a some sample in the DART mass spectrometer of 1st Example. The flowchart which shows an example of the processing operation at the time of analyzing the data collected by the measurement shown in FIG. Schematic which shows an example of the during-measurement screen displayed on the screen of a display part during measurement execution in the DART mass spectrometer of 1st Example. The figure which shows an example of the chromatogram (total ion chromatogram) displayed in real time during the measurement execution in the DART mass spectrometer of 1st Example. The figure which shows an example of the sample list | wrist produced in advance in the DART mass spectrometer of 1st Example. Schematic which shows an example of the screen during a measurement in the case of inputting the measurement time range by click operation with a cursor in the DART mass spectrometer of 1st Example. The figure which shows an example of the chromatogram automatically displayed at the time of an analysis in the DART mass spectrometer of 1st Example. The figure which shows an example of the chromatogram and mass spectrum which are displayed after the subtraction process of a mass spectrum in the DART mass spectrometer of 1st Example. The figure which shows an example of the compound information used for peak identification in the DART mass spectrometer of 1st Example. The figure which shows the example of a display when performing the automatic expansion display of the mass spectrum in the DART mass spectrometer of 1st Example. The figure which shows the example of a display which attached | subjected the specific mark with respect to the peak detected as a result of the difference analysis about the example shown in FIG. The figure which shows the example which tabulated the signal strength with respect to the peak detected as a result of the difference analysis about the example shown in FIG. 9, and the signal strength difference between different samples. The block diagram of the principal part of the DART mass spectrometer which is 2nd Example of this invention. The flowchart which shows an example of the conventional measurement procedure in the case of performing the measurement with respect to a some sample using a DART mass spectrometer. The flowchart which shows an example of the analysis procedure at the time of analyzing the data obtained by the measurement procedure shown in FIG.

[First embodiment]
A DART mass spectrometer according to a first embodiment of the present invention will be described with reference to the accompanying drawings.
FIG. 1 is a configuration diagram of a main part of the DART mass spectrometer of the first embodiment.
In the mass spectrometer of the present embodiment, the degree of vacuum increases stepwise between the ionization region 20 opened to the atmosphere and the analysis chamber 23 which is a high vacuum atmosphere evacuated by a high performance vacuum pump (not shown). The multistage differential exhaust system having the first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22 is provided. The ionization region 20 and the first intermediate vacuum chamber 21 communicate with each other through a small diameter ion introduction tube 26. The DART ionization unit 10 is disposed in the ionization region 20 so as to face the inlet opening 26a of the ion introduction tube 26, and the sample 25 to be analyzed is placed between the inlet opening 26a and the DART ionization unit 10 when the measurement is performed. Is inserted.

The DART ionization unit 10 has three chambers: a discharge chamber 11, a reaction chamber 12, and a heating chamber 13. A gas introduction tube 14 for introducing an inert gas such as helium is connected to the first-stage discharge chamber 11, and a needle electrode 15 is disposed inside the discharge chamber 11. A heater (not shown) is attached to the heating chamber 13 at the final stage, and a grid electrode 19 is provided to the nozzle 18 that is an outlet of the heating chamber 13.

The first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22 are separated by a skimmer 28 having a small hole (orifice) at the top, and each of the first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22 includes Ion guides 27 and 29 are provided for transporting ions to the subsequent stage while converging ions. In this example, the ion guide 27 uses a plurality of electrode plates arranged along the ion optical axis C as one virtual rod electrode, and a plurality of (for example, four) virtual plates around the ion optical axis C. It is the structure which has arrange | positioned the target rod electrode. The ion guide 29 has a configuration in which a plurality (for example, eight) of rod electrodes extending in the direction along the ion optical axis C are arranged around the ion optical axis C. However, the configuration of the ion guides 27 and 29 is not limited to this, and can be changed as appropriate. Inside the analysis chamber 23, a quadrupole mass filter 30 that separates ions according to the mass-to-charge ratio m / z and an ion detector 31 that detects ions that have passed through the quadrupole mass filter 30 are installed. . The detection signal from the ion detector 31 is digitized by an analog-digital converter (ADC) 32 and then sent to the control / processing unit 40.

The analysis control unit 33 receives the instruction from the control / processing unit 40 and controls the operation of each unit of the mass spectrometer other than the DART ionization unit 10 when performing the measurement. Further, the DART drive control unit 34 controls the operation of the DART ionization unit 10 when performing the measurement. The control / processing unit 40 performs overall control and data processing of the entire apparatus. As functional blocks characteristic of the present embodiment, a real-time chromatogram creation unit 41, a comment input reception unit 42, a data file creation Unit 43, data storage unit 44, chromatogram creation unit 46, mass spectrum creation unit 47, spectrum subtraction unit 48, spectrum peak identification unit 49, known component information storage unit 50, difference analysis unit 51, difference information display processing unit 52, Etc. Connected to the control / processing unit 40 are an input unit 60 operated by a user (a worker in charge of analysis) and a display unit 61 which is a display monitor. In general, the control / processing unit 40 is configured to achieve each function by using a personal computer as a hardware resource and executing dedicated control / processing software installed in advance in the computer. Further, since the operation of the DART ionization unit 10 does not need to be linked to the mass spectrometer, the DART drive control unit 34 can be configured to be controlled by an independent control system different from the control / processing unit 40. .

A mass analysis operation on a sample in the DART mass spectrometer of the present embodiment will be schematically described.
In the DART ion source 10, when helium is supplied into the discharge chamber 11 through the gas introduction tube 14 and a high voltage is applied to the needle electrode 15 with the helium filled in the discharge chamber 11, the needle electrode 15 is grounded. Discharge occurs between the partition walls 16 that are at a potential. This discharge changes the ground singlet molecular helium gas (1 ¹ S) into a mixture of helium ions, electrons, and excited excited triplet molecular helium (2 ³ S). This mixture enters the next reaction chamber 12, but the charged helium ions and electrons are blocked in the reaction chamber 12 by the action of the electric field generated by the voltage applied to the

partition walls

16 and 17 of the reaction chamber 12. Only excited triplet molecular helium that is electrically neutral is fed into the heating chamber 13.

The excited triplet molecular helium heated to a high temperature in the heating chamber 13 is ejected from the nozzle 18 to the ionization region 20 through the grid electrode 19. The heated excited triplet molecular helium penning ionizes water molecules in the atmosphere present in the ionization region 20. The water molecule ions thus generated are in an excited state. Since the gas containing excited triplet molecular helium is high temperature, when this gas is blown onto the sample 25 placed in front of the nozzle 18, the component molecules in the sample 25 are vaporized. When water molecule ions in an excited state act on component molecules generated by vaporization, a reaction occurs to ionize the component molecules. In this manner, the DART ionization unit 10 can ionize a solid or liquid sample as it is, that is, in a state of being placed on the spot.

The generated ions are sucked into the ion introduction tube 26 by the pressure difference between the ion region 20 and the first intermediate vacuum chamber 21 and sent to the first intermediate vacuum chamber 21. The ions are converged by the ion guide 27, sent to the second intermediate vacuum chamber 22 through the orifice at the top of the skimmer 28, and further converged by the ion guide 29 and sent to the analysis chamber 23. A predetermined voltage is applied to the four rod electrodes constituting the quadrupole mass filter 30, and only ions having a mass-to-charge ratio corresponding to the voltage pass through the quadrupole mass filter 30 to the ion detector 31. Incident. The ion detector 31 outputs a detection signal corresponding to the amount of incident ions. Therefore, for example, when the voltage applied to the four rod electrodes constituting the quadrupole mass filter 30 is scanned within a predetermined range, the mass-to-charge ratio of ions that can pass through the quadrupole mass filter 30 is a predetermined mass-to-charge ratio. Scanned in range. The control / processing unit 40 can obtain a mass spectrum indicating the signal intensity of ions over a predetermined mass-to-charge ratio range based on the detection signals sequentially obtained at this time.

As described above, one of the features of this DART mass spectrometer is that the sample 25 is subjected to mass analysis only by passing the sample 25 over the gas flow ejected from the nozzle 18 of the DART ionization unit 10 and the result is obtained. It is to be obtained.

Next, an example of the operation of the operator and the operation of the apparatus when measuring three samples as the sample 25 by the DART mass spectrometer of the present embodiment will be described. FIG. 2 is a flowchart showing the measurement procedure and operation at this time.
When the operator performs a predetermined operation with the input unit 60, scan measurement over a predetermined mass-to-charge ratio range is started under the control of the analysis control unit 33 in response to an instruction from the control / processing unit 40. The operator waits for a few minutes (about 3 minutes in this example) from the start of measurement without inserting the sample into the measurement position. Thereby, measurement in a state where the sample 25 is not at the measurement position, that is, blank measurement is performed.

FIG. 4 is a schematic diagram illustrating an example of the in-measurement screen 100 displayed on the screen of the display unit 61 during measurement execution. In the measuring screen 100, a chromatogram display column 101 and a comment information input table 102 are arranged.
When the measurement is started, the real-time chromatogram creation unit 41 in the control / processing unit 40 receives the detection data digitized by the analog-to-digital converter 32, and the total ion chromatogram (in the following description, the total ion chromatogram is described). The gram is sometimes simply referred to as “chromatogram”) and displayed in the chromatogram display column 101. Each time scan measurement is performed and new data is obtained, the curve of the chromatogram displayed in the chromatogram display column 101 is updated. As shown in FIG. 5, during the blank measurement, a curve indicating background such as noise appears.

The operator inputs the name of the sample being measured and the measurement start time and end time for the sample in the comment information input table 102 displayed together with the chromatogram (step S2). As shown in FIG. 4, the comment information input table 102 is provided with a sample name input field 102a, a measurement start time input field 102b, and a measurement end time input field 102c. By selecting a field to be input by a device or the like and inputting an appropriate text from the keyboard, desired information may be input in each field. In the case of blank measurement, “blank” may be entered in the sample name input field.

When a predetermined time has elapsed from the measurement start time, the operator inserts the first sample (sample 1) into the measurement position, thereby performing measurement on the sample (step S3). Then, since ions generated from this sample begin to be introduced into the first intermediate vacuum chamber 21 through the ion introduction tube 26, the chromatogram displayed in the chromatogram display column 101 in a substantially real time has a peak as shown in FIG. Begins to appear. As in step S2, the operator inputs the name of the sample being measured and the measurement start time and end time for the sample in the comment information input table 102 (step S4). The measurement start time and measurement end time for the sample may be input by the operator visually reading the start point and end point of the peak appearing in the chromatogram.

After the operator inserts one sample into the measurement position for a predetermined time and completes the measurement, if there is an unmeasured sample (Yes in step S5), the process returns to step S3, and another sample that has not been measured is measured. And perform measurements on the sample. Thereby, as shown in FIG. 5, the second peak appears in the chromatogram. Then, the operator inputs the sample name and the measurement start time / end time for the sample.

If the processes of steps S3 and S4 are performed for all the prepared samples, the operator instructs the end of the measurement by performing a predetermined operation with the input unit 60. Then, the analysis control unit 33 controls each unit so as to end the measurement. In addition, the comment input receiving unit 42 collects sample information such as the sample name input to the comment information input table 102 at that time and the measurement start time / end time of each sample. The data file creation unit 43 stores all the data obtained by a series of measurements in one data file, and also stores the sample information collected by the comment input reception unit 42 in the same data file. Is stored in the data storage unit 44 (step S6).
As a result, a data file storing both the mass spectrum data obtained by the blank measurement and the measurement of a plurality of samples and the information of the sample name and the measurement start time / end time of the measured sample is stored.

As described above, the operator may directly write the sample name or the like in each column of the comment information input table 102, but a simpler input method may be used. For example, as shown in FIG. 6, a sample list in which information such as a sample name, a molecular weight corresponding to the sample, and a composition formula is registered in advance is stored, and a sample is appropriately selected from the sample list. A sample name may be entered. Further, instead of a list including various information as shown in FIG. 6, a pull-down menu in which only sample names are listed may be displayed so that sample names can be selected from them. In addition, a sample list as shown in FIG. 6 is arranged on the measuring screen 100 or displayed as another screen on the screen 100, and an appropriate sample name is displayed by drag and drop operation from the list. May be entered.

Also, it is convenient that the measurement start time and end time can be input by clicking with a cursor (mouse pointer) displayed superimposed on the chromatogram displayed in the chromatogram display column 101. FIG. 7 is a schematic view showing an example of the in-measurement screen 100 in this case. The operator operates the pointing device as the input unit 60 to move the arrow-like cursor 103 displayed in the chromatogram display column 101 to a predetermined position, and performs a click operation. Then, the comment input receiving unit 42 acquires time information corresponding to the clicked position, and the time is automatically entered in the measurement start time input field 102b or the measurement end time input field 102c in the comment information input table 102. Write. In FIG. 7, the position of the cursor when specifying the measurement start time for the sample 1 is indicated by a solid line, and the position of the cursor when specifying the measurement end time is indicated by a dotted line. Such a graphical operation reduces the labor of input by the operator.

Subsequently, an example of the operation of the operator and the operation of the apparatus when performing analysis on the data in a state where the measurement data for a plurality of samples is stored in the data storage unit 44 as described above will be described. FIG. 3 is a flowchart showing the processing operation at this time.

When the operator designates the data file name from the input unit 60 and instructs the start of analysis, the chromatogram creation unit 46 reads the designated data file from the data storage unit 44. Then, a total ion chromatogram over the entire measurement time range is created based on the measurement data stored in the file. Also, from the sample information stored in the same file, the sample name and the measurement time range of that sample (the period from the measurement start time to the measurement end time) are recognized and appear in each measurement time range on the chromatogram. The sample name is associated with the peak, and the sample name is pasted at a predetermined position near the peak top of the peak. Then, a chromatogram with a sample name assigned to each peak is displayed on the screen of the display unit 61 (step S11). FIG. 8 is an example of the chromatogram created and displayed in this way.

Next, the mass spectrum creation unit 47 detects the peak top of the peak for each measurement time range, extracts the mass spectrum data acquired at the time corresponding to the peak top, and creates a mass spectrum. That is, in the example of FIG. 8, mass spectrum data at a time corresponding to the peak top positions of the peaks of the three samples is extracted, and mass spectra are respectively created based on the data. Further, the mass spectrum creation unit 47 calculates the average value of the signal intensity for each mass to charge ratio with respect to the mass spectrum data obtained in the entire measurement time range whose sample name is “blank” or in a predetermined time range therein. Thus, a background mass spectrum that is an average of the mass spectra for the blank measurement is obtained. For each sample, the spectrum subtraction unit 48 subtracts the common background mass spectrum from the mass spectrum for the sample to obtain a mass spectrum from which the background has been removed. Then, a sample name corresponding to each mass spectrum from which the background has been removed is added and displayed on the screen of the display unit 61 together with the chromatogram (step S12). FIG. 9 is a diagram showing an example of the chromatogram and mass spectrum displayed in this way.
Although the mass spectra for all samples are listed here, the mass spectra for only the selected sample may be displayed, or the mass spectra may be selectively displayed by switching tabs instead of displaying the list. May be displayed.

Further, the spectrum subtraction unit 48 may calculate a difference between two designated mass spectra instead of subtracting a common background mass spectrum from a mass spectrum for one sample, and obtain a difference mass spectrum. . For example, the mass spectrum for sample 2 without background removal is subtracted from the mass spectrum for sample 1 without background removal, and the sample names of the two samples are added to the resulting difference mass spectrum. It may be displayed on the screen of the display unit 61. Since the common background is removed from the difference mass spectrum calculated in this way, the operator can accurately grasp the difference in signal intensity for each mass-to-charge ratio between sample 1 and sample 2 by displaying this difference mass spectrum. can do.

The known component information storage unit 50 stores in advance information about a compound that is predicted to be contained. FIG. 10 is a diagram showing an example of this compound information. In this example, for each compound, in addition to information such as molecular weight, molecular ion mass-to-charge ratio, composition formula, and structural formula, it is included in adduct information such as mass-to-charge ratio of adduct ions such as Na adducts and NH ₃ adducts. It is. Such information can be generated based on various known compound databases. An existing compound database may be used as it is. The adduct information may be automatically created from information such as molecular weight.

The spectrum peak specifying unit 49 performs peak detection on the mass spectrum after background removal for each sample calculated in step S12, and the mass-to-charge ratio information of the detected peak is stored in the known component information storage unit 50. Identify the peaks in light of the compound information. Then, for the identified peak, that is, the peak confirmed to be a certain compound, at least one of information such as the name, molecular weight, mass-to-charge ratio, and structural formula of the compound is displayed on the mass spectrum. Displayed in the vicinity of the peak (step S13). At this time, a peak in a mass-to-charge ratio corresponding to an adduct ion such as an Na adduct or NH ₃ adduct is also detected, and if such a peak is detected, compound information corresponding to the adduct ion is displayed.

In addition, when the interval between adjacent peaks in the mass spectrum is too narrow and the compound information displays overlap, or when the peak signal intensity is below a predetermined value and it is difficult to see which compound information is in which peak For example, it is preferable to recognize that such a display state is present, automatically enlarge a part of the mass spectrum, and display the compound information in association with the peak on the enlarged mass spectrum. FIG. 11 shows an example in which the enlarged mass spectrum view is displayed in the original (not enlarged) display frame of the mass spectrum, but the enlarged mass spectrum view may be out of the display frame of the original mass spectrum. .

Moreover, the difference analysis part 51 performs the process which extracts the difference (or commonality) of the mass spectrum after the background removal with respect to several samples on the conditions set beforehand. The difference in mass spectrum here is, for example, a difference in signal intensity at the same mass-to-charge ratio, a difference in mass-to-charge ratio between peaks appearing at a large signal intensity, or the like. If there is a difference in signal intensity or mass-to-charge ratio, a display is made on the mass spectrum so that the difference can be easily identified (step S14).
For example, the difference analysis unit 51 sets a threshold value of signal intensity, and extracts all mass-to-charge ratios whose signal intensity exceeds the threshold value in a mass spectrum for any sample. Then, a difference in signal intensity in the mass-to-charge ratio is calculated among a plurality of designated samples.

For the mass spectra for the three samples shown in FIG. 9, assuming that the signal intensity threshold is set to 400,000, the three mass-to-charge ratios of m / z / 150.2, m / z 192.2, and m / z 391.2 are the threshold values. Over. If the difference in signal intensity in these mass-to-charge ratios is large, the mass-to-charge ratio is a compound that exists specifically in a certain sample, and conversely, if the difference in signal intensity is small, it exists in any sample in common. It can be said that it is a non-specific compound. In the example of FIG. 9, m / zm150.2 is a compound specifically detected in sample 3, m / z 192.2 is a compound detected in common in sample 1 and sample 2, and m / z 391.2 It can be seen that is a compound specifically detected in sample 1. Therefore, a peak corresponding to a compound that is specifically detected and a peak corresponding to a compound that is commonly detected in at least two samples are displayed in colors that are easily distinguishable from other peaks. Thus, if the compound information is displayed as described above for the peak displayed in a color different from that of the other peaks, the worker exists in one of a plurality of samples as a specific compound or in common. Compounds and the like can be easily grasped.

Of course, for example, the difference analysis unit 51 may calculate the difference in signal intensity for all mass-to-charge ratios among a plurality of designated samples without setting a threshold value for the signal intensity. In addition to making the peak color corresponding to the compound specifically detected in one sample and the peak color corresponding to the compound commonly detected in multiple samples different from other peaks, such peak A specific mark may be displayed in the vicinity of or near the compound information display associated with such a peak. FIG. 12 shows an example in which a specific mark is attached to the peak detected under the above-described conditions for the example shown in FIG. In this example, the peak m / z 150.2 detected specifically in sample 3 is an asterisk, the peak m / z 391.2 specifically detected in sample 1 is a triangle, and sample 1 and sample The peak of m / z 192.2 detected in common with 2 is marked with a circle.

Further, the difference information display processing unit 52 creates a table based on information about the specific compound or common compound extracted by the difference analysis unit 51, and further extracts ion chromatograms at mass-to-charge ratios corresponding to these compounds. A gram is created (step S15). FIG. 13 is an example in which the signal intensity with respect to the peak detected under the above-described conditions for the example shown in FIG. 9 and the signal intensity difference between different samples are tabulated. Then, the created table and extracted ion chromatogram are displayed on the screen of the display unit 61 (step S16). By displaying a table as shown in FIG. 13, the operator can quantitatively grasp the signal intensity difference. Also, the operator compares the peak appearing in the extracted ion chromatogram with the position of the peak appearing in the total ion chromatogram, so that the compound is certainly sample-specific or common to multiple samples. Can be confirmed.

As described above, in the DART mass spectrometer according to the present embodiment, when analyzing measurement data collected by measurement, an operator specifies a data file to be analyzed, and sets analysis-related conditions as necessary. Only automatically removes the background of the mass spectrum, identifies the peaks on the mass spectrum, analyzes the differences between multiple samples, and so on. Thereby, the burden on the worker at the time of data analysis is greatly reduced, and variations in results due to differences in the skill level and skill of the worker can be eliminated.

[Second Embodiment]
A DART mass spectrometer according to a second embodiment of the present invention will be described with reference to the block diagram shown in FIG. In FIG. 14, the same or corresponding components as those in the DART mass spectrometer according to the first embodiment shown in FIG.
The difference between the DART mass spectrometer of the second embodiment and the DART mass spectrometer of the first embodiment is that a peak detector 45 is newly added to the control / processor 40.

As described above, in the DART mass spectrometer of the first embodiment, sample information such as a sample name and measurement time information (measurement start time and end time) for each sample are obtained by performing some operation by an operator during measurement. Entered. On the other hand, in the DART mass spectrometer of the second embodiment, the measurement start time and the measurement end time are obtained from the result of automatic peak detection by the peak detector 45, regardless of the operator's operation. Is done.

That is, when measurement is started, the peak detection unit 45 determines the peak start point based on the slope, peak height, peak width, etc. of the chromatogram curve created by the real-time chromatogram creation unit 41 every moment. And recognize the end point. The method is the same as the detection of a peak on a normal chromatogram. Each time the peak start time and end time for one sample are obtained, the information is automatically stored in the measurement start time input field 102b and the measurement end time input field 102c in the comment information input table 102 shown in FIG. To write. As a result, the operator only has to perform the operation of entering the sample name or selecting from the list in addition to the operation of holding the sample over the measurement position, and the burden on the operator when performing the measurement is reduced.

In the above embodiment, a DART ion source is used as an ion source. However, ambient that can be measured in situ in an atmospheric pressure atmosphere without pretreatment of a solid or liquid sample other than DART. Various ionization methods called ionization can be used. Specifically, an ion source based on an ionization method such as the DESI method, the PESI method, the ELDI method, or the ASAP method described above can be used.

As can be seen from the above description, the data that can be analyzed by the DART mass spectrometer according to the first embodiment shown in FIG. 3 corresponds to the measurement data, the sample information, and the measurement time information. As long as it is attached, the data is not necessarily obtained by the measurement procedure as shown in FIG. That is, sample information such as sample name is not input by the operator's operation, but can be applied to a mass spectrometer that performs measurement while automatically selecting a sample according to a sample table listing sample names, for example. Technology. In addition, the ion source is not limited to the ion source as described above, and the liquid chromatograph mass spectrometer or gas chromatograph mass spectrometer in which a liquid chromatograph or a gas chromatograph is connected to the preceding stage of the mass spectrometer is used as described above. Data analysis processing techniques can also be adopted.

Furthermore, in other respects, it is obvious that modifications, changes, additions and the like as appropriate within the scope of the present invention are included in the scope of the claims of the present application.

DESCRIPTION OF SYMBOLS 10 ... DART ionization unit 11 ... Discharge chamber 12 ... Reaction chamber 13 ... Heating chamber 14 ... Gas introduction tube 15 ... Needle electrode 16 ... Inlet side partition 17 ... Outlet side partition 18 ... Nozzle 19 ... Grid electrode 20 ...

Ionization region

21,22 ... Intermediate vacuum chamber 23 ... Analysis chamber 25 ... Sample 26 ... Ion introduction tube 26a ... Inlet opening 27, 29 ... Ion guide 28 ... Skimer 30 ... Quadrupole mass filter 31 ... Ion detector 32 ... Analog / digital converter 33 ... Analysis Control unit 40 ... Control / processing unit 41 ... Real time chromatogram creation unit 42 ... Comment input acceptance unit 43 ... Data file creation unit 44 ... Data storage unit 45 ... Peak detection unit 46 ... Chromatogram creation unit 47 ... Mass spectrum creation unit 48 ... Spectrum subtraction part 49 ... Spectrum peak specifying part 50 ... Known component information storage part 51 ... Difference analysis part 52 ... Different information display processing unit 60 ... input section 61 ... display unit

Claims

A mass spectrometer that performs measurement on a sample placed at a predetermined measurement position in an atmospheric pressure atmosphere in real time,
a) a comment input receiving unit that receives input of comment information including at least sample information for specifying a sample to be measured by a user during measurement execution;
b) The comment information received by the comment input receiving unit is stored in a data file in which measurement data collected at the time of the reception is stored, or in another file associated with the data file. A data storage unit to store;
A mass spectrometer comprising:
The mass spectrometer according to claim 1,
The comment input receiving unit receives sample information selected by a user from a list in which a plurality of sample information is registered in advance as one of the comment information.
The mass spectrometer according to claim 1 or 2,
The comment input receiving unit receives, in addition to the sample information, measurement time information for a sample as one of the comment information.
The mass spectrometer according to claim 3,
A measurement chromatogram display processing unit that creates a chromatogram based on measurement data in real time and renders it on the display screen is further provided.
The comment input receiving unit receives, as the time information, a time corresponding to a position instructed by a user in a chromatogram drawn on the display screen.
The mass spectrometer according to claim 1 or 2,
A chromatogram creation section that creates a chromatogram in real time based on measurement data; and a peak detection section that detects a peak in the chromatogram,
The data storage unit stores the time information obtained from the detection result by the peak detection unit in the data file together with the comment information received by the comment input reception unit as the measurement time information for the sample, or corresponds to the data file A mass spectrometer characterized in that it is stored in a separate file attached.
A mass spectrometer according to any one of claims 1 to 5,
Display processing for displaying at least a part of the comment information received by the comment input receiving unit at an appropriate position on a chromatogram or mass spectrum created based on data obtained by measurement and displayed on a display screen The mass spectrometer further comprising a unit.
The mass spectrometer according to claim 1,
A spectrum subtracting unit that subtracts a mass spectrum obtained by blank measurement without a sample from a mass spectrum obtained by measurement in a state where the sample is present, identified based on the comment information received by the comment input acceptance unit; ,
A mass spectrum display processing unit for displaying the mass spectrum subtracted by the spectrum subtraction unit;
A mass spectrometer further comprising:
The mass spectrometer according to claim 7,
A difference information extraction unit for extracting information on the difference between the subtracted mass-mass spectra respectively obtained for two or more different samples;
A difference information display unit for displaying the difference information extracted by the difference information extraction unit;
A mass spectrometer further comprising:
The mass spectrometer according to claim 7,
A storage unit for storing compound information in which the type of compound and mass-to-charge ratio information are associated;
A compound specifying unit for specifying a compound by comparing the mass-to-charge ratio of the peak on the mass spectrum with the compound information stored in the storage unit;
A display unit for displaying information indicating the compound specified by the compound specifying unit in association with a peak and / or mass spectrum on a chromatogram;
A mass spectrometer further comprising:
The mass spectrometer according to any one of claims 1 to 9,
A mass spectrometer comprising an ion source based on a real-time direct ionization method.