WO2015189945A1 - 分析装置用制御装置 - Google Patents
分析装置用制御装置 Download PDFInfo
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/24—Automatic injection systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/86—Signal analysis
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/0092—Scheduling
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8804—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 automated systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00584—Control arrangements for automatic analysers
- G01N35/0092—Scheduling
- G01N2035/0094—Scheduling optimisation; experiment design
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/72—Mass spectrometers
- G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
Definitions
- the present invention relates to a control device for controlling an analyzer such as a liquid chromatograph, a gas chromatograph, a liquid chromatograph mass spectrometer, a gas chromatograph mass spectrometer, and more particularly, a sample automatically from a number of samples prepared in advance.
- the present invention relates to a control device suitable for an automatic analyzer that performs analysis on a plurality of samples continuously by combining an autosampler that selects and collects and an analyzer that analyzes a sample collected by the autosampler.
- the analysis conditions include the flow rate of the mobile phase, the gradient conditions, the column temperature, and the like
- the data analysis processing conditions include a retention time, a peak waveform processing parameter, a calibration curve, and the like.
- the analysis conditions include data analysis processing conditions.
- the optimal analysis conditions differ from compound to compound (in some cases, results with the same degree of accuracy may be obtained for a plurality of compounds under the same analysis conditions). Therefore, in the commissioned analysis office described above, the manager in charge usually creates appropriate analysis methods for various compounds to be analyzed in advance, and stores the analysis method file in the storage device of the computer ( (See Non-Patent Document 1, etc.). Then, when performing an automatic analysis on a large number of samples, the operator selects one or a plurality of analysis methods from the registered analysis methods on the basis of an instruction sheet or the like and instructs the execution of the analysis. .
- Such an analysis method using a conventional analyzer has the following problems. Now, for example, consider a case in which the specimen is the blood or urine of the subject and a known drug or metabolite contained in the specimen is quantified. In such a test, although the types of target compounds are limited, the types of compounds to be quantified are often different for each specimen.
- the analysis using the analysis method selected first is performed for each sample, that is, is performed omnidirectionally. Analysis using an analytical method created for a non-existing compound will also be performed on the sample. Such an analysis does not really make sense and simply uses the sample in vain. In addition, the time required for analysis is wasted, and in LC and GC, the mobile phase and carrier gas are also wasted.
- this method it is possible to quantitate a plurality of compounds contained in one sample in one analysis, but it is possible to detect a plurality of compounds within a limited time during which the target compound is eluted. Since this must be done, the detection time per compound is shortened, resulting in reduced sensitivity.
- An object of the present invention is to provide a control device for an analyzer that can execute an analysis while suppressing the amount of consumption materials used for analysis such as a mobile phase and a carrier gas.
- the present invention made to solve the above problems is for an analyzer that controls the operation of an analyzer that performs analysis on a single sample containing one or a plurality of compounds or performs continuous analysis on a plurality of the samples.
- a control device a) a sample information acquisition unit that acquires sample information indicating one or more target compounds that may be included in the sample for each sample to be analyzed; b) For each analysis method in which the analysis conditions for performing the analysis are described, information indicating the compound assumed in the analysis using the analysis method included in the analysis method is obtained, and the analysis method A method information acquisition unit for creating method information in which a compound and a compound are associated; c) In the case of analysis for one sample or continuous analysis for a plurality of samples, when one or a plurality of samples actually used for the analysis are designated by the operator, based on the sample information by the sample information acquisition unit, Identify the target compound in each of the specified samples, identify the analysis method corresponding to the specified target compound based on the method information by the method information acquisition unit, and use
- the analyzer is not particularly limited as long as it is an apparatus capable of performing an analysis on a compound contained in a specimen (sample), but a typical example Examples thereof include liquid chromatograph (LC), gas chromatograph (GC), liquid chromatograph mass spectrometer (LC-MS), gas chromatograph mass spectrometer (GC-MS) and the like.
- the analysis method includes analysis conditions relating to the separation performance in the chromatograph, for example, the flow rate of the mobile phase, the column temperature, and the like in the case of LC.
- the analysis method includes analysis conditions in the mass spectrometer, such as a scan speed and a scan range (mass-to-charge ratio range) when performing scan measurement.
- the analysis method includes, for example, collision energy and MRM transition.
- the analyzer When performing continuous analysis on a plurality of samples, the analyzer as described above automatically selects a sample prepared in advance, collects a part of the selected sample, and uses it for analysis.
- a sample supply device called a sampler is included.
- the analysis device may include a data processing device that performs analysis processing on data obtained by performing analysis on a specimen to identify or quantify a compound.
- the analysis method includes data analysis processing conditions used when performing the data processing.
- the sample information may be created by a business establishment or an organization that performs analysis by the analyzer, but is external, that is, a business that performs analysis by the analyzer It may be given from an establishment or organization other than the establishment or organization. For example, when a medical institution requests a lot of specimens, specimen information is created in the medical institution.
- Such sample information may be stored in a storage device that is a part of the control device for the analyzer, or stored in an external storage device and can be accessed seamlessly from the control device for the analyzer. Also good.
- the “specimen information acquisition unit” in the control apparatus for analyzer according to the present invention is means for reading out corresponding information from the internal storage device.
- the “specimen information acquisition unit” in the control apparatus for analyzer according to the present invention is a means for accessing an external storage device through a communication line, reading out the corresponding information, and receiving it.
- Analytical methods are generally created by managers who have specialized knowledge of analysis and have high authority for analysis at establishments and institutions that conduct analysis using this analyzer. Of course, it is also conceivable that an analysis device manufacturer or the like develops an analysis method suitable for analyzing a specific type of sample and provides it to a user office or organization.
- the analytical method includes a calibration curve for quantification.
- a calibration curve is created corresponding to a compound. Therefore, when a calibration curve is included in an analytical method, the analytical method is usually specialized for a certain compound, and the assumed compound For example, information such as a compound name is included. Therefore, for example, when a plurality of analysis methods that may be used for analysis on one or a plurality of specimens are designated, the method information acquisition unit reads information on the compounds included in the analysis methods, and the analysis method and the compound Create method information that indicates the correspondence with. In addition, method information indicating the correspondence between the analysis method and the compound may be created for all created or given analysis methods regardless of the designation of the analysis method.
- the correspondence between the position of the vial on the sample plate loaded in the autosampler and the identification information of the sample to be analyzed, such as the sample number, is analyzed. Specified by the operator responsible for the work.
- the optimum method determination unit identifies one or a plurality of target compounds in each sample to be analyzed based on the sample information. Furthermore, an analysis method corresponding to the identified target compound is identified based on the method information. As a result, the association with one or a plurality of analysis methods suitable for use in the analysis for each specimen is found, and information on the combination is created.
- the information created by the optimum method determination unit can be used as part of information called an analysis schedule or batch table that defines the order of analysis in continuous analysis, for example.
- an analysis method suitable for analyzing a target compound contained in a sample to be analyzed from among a plurality of prepared or designated analysis methods. Is automatically selected, and information in which the specimen and the analysis method are associated with each other is created. Therefore, even when an operator who lacks specialized knowledge about the analysis works, it is possible to prevent the analysis on the sample from being performed using an analysis method that does not correspond to the target compound in the sample.
- an analysis method suitable for analyzing the target compound in the sample to be analyzed may not be prepared. Therefore, in the control apparatus for an analyzer according to the present invention, preferably, at least one target compound for which there is no corresponding analytical method among target compounds respectively contained in one or a plurality of specimens designated as analysis targets. If there is at least one target compound for which there is a corresponding analytical method, a warning is issued while performing the analysis of the target compound in the sample, while there is a target for which the corresponding analytical method exists. When there is no compound, an error notification may be configured.
- the sample is analyzed using an analysis method corresponding to the target compound, and the target compound is quantified. Results can be obtained.
- the operator can recognize by a warning notification that there is a compound that has not been analyzed because there is no corresponding analysis method. Further, when the analysis is not performed for all target compounds in the sample because the corresponding analysis method does not exist, the operator can recognize this by error notification. Therefore, in any case, it is possible to avoid the analysis of a certain target compound in the sample by an inappropriate analytical method.
- the analysis conditions included in each of the plurality of analysis methods Confirm that the analysis conditions of some target compounds that are partly the same and not the same do not affect the analysis results of the target compounds that correspond to the multiple analytical methods.
- the analysis method included in the analysis method may be integrated with an analysis method integration unit that creates temporary analysis methods corresponding to a plurality of target compounds.
- the separation conditions in LC such as the flow rate of the mobile phase are the same in a plurality of analytical methods, and the retention times of the target compounds should not overlap.
- the separation conditions contained in the plurality of analysis methods can be integrated to create a temporary analysis method corresponding to a plurality of target compounds.
- the analyzer control device typically has a configuration in which predetermined control software is installed in advance in a personal computer provided with an input unit and a display unit.
- predetermined control software is installed in advance in a personal computer provided with an input unit and a display unit.
- the above and the functions can be realized by the control software operating on the computer.
- control device for an analyzer it is possible to avoid performing analysis on the sample using an analysis method that does not correspond to the target compound in the sample, and therefore, it is possible to perform useless analysis.
- the efficiency of analysis work can be improved by shortening the analysis time.
- the analysis cost can be reduced by reducing the amount of consumption materials such as specimens and mobile phases.
- the operator does not need specialized knowledge about analysis in such work, which is advantageous in terms of reducing analysis costs, and providing analysis results that are delayed due to work mistakes and inappropriate results. Can be prevented.
- FIG. 1 is a schematic configuration diagram of an embodiment of an LC-MS analysis system using an analyzer control device according to the present invention.
- the flowchart which shows the operation
- the figure which shows an example of the sample information in the LC-MS analysis system of a present Example.
- FIG. 1 is a schematic configuration diagram of an LC-MS analysis system according to this embodiment.
- This LC-MS analysis system includes a liquid chromatograph mass analysis unit (LC-MS unit) 1 for separating and detecting compounds contained in a sample solution (specimen) in time, and a large number of vials 22 prepared in advance.
- An autosampler 2 that selects and supplies the sample solution in the vial 22 to the LC-MS unit 1 and a control unit 3 that controls these operations are provided.
- the LC-MS unit 1 includes a mobile phase container 11 in which a mobile phase is stored, a pump 12 that sucks the mobile phase in the mobile phase container 11 and delivers it at a substantially constant flow rate, and a sample in the mobile phase.
- An injector 13 for injecting the solution, a column 14 for separating various compounds contained in the sample solution injected into the mobile phase in the time direction, and a tandem four which is a detector for sequentially detecting the various compounds separated by the column 14
- a data processing unit 16 for processing a detection signal obtained by the tandem quadrupole mass spectrometer 15.
- the tandem quadrupole mass spectrometer 15 is a front quadruple that separates an atmospheric pressure ion source such as an electrospray ion source and ions generated by the atmospheric pressure ion source according to a mass-to-charge ratio.
- a polar mass filter, a collision cell that dissociates ions that have passed through the mass filter by a technique such as collision-induced dissociation (CID), and product ions that are generated by being dissociated by the collision cell are separated according to a mass-to-charge ratio.
- the autosampler 2 includes a tray-like sample plate 21 on which a number of vials 22 each containing a sample solution are placed, and a plate moving unit that moves the sample plate 21 in the X-axis direction and the Y-axis direction orthogonal to each other. 23, and a sample collection unit 24 that includes a needle, a mechanism for raising and lowering the needle, and sucks a predetermined amount of the sample solution in the vial 22 at a predetermined sample suction position.
- the sample solution collected by the sample collection unit 24 is sent to the injector 13 of the LC-MS unit 1 and injected into the mobile phase or discarded into a waste liquid unit (not shown).
- the control unit 3 to which the input unit 4 and the display unit 5 as a user interface are connected includes an analysis control unit 30 that sends control signals to the LC-MS unit 1 and the autosampler 2 in order to perform analysis, and an analysis method creation process A unit 31, a method information creation processing unit 32, a sample registration processing unit 33, a used method automatic determination unit 34, an analysis schedule creation unit 35, and a storage unit 36 are included as functional blocks.
- the storage unit 36 includes storage areas such as a specimen information storage unit 361, an analysis method storage unit 362, a method information storage unit 363, and an analysis schedule storage unit 364.
- the control unit 3 uses the personal computer or a higher-performance workstation as hardware resources, and executes the dedicated control software installed in the computer in advance on the computer to realize the functions of the above blocks. It can be set as a structure. Similarly, the data processing unit 16 can be realized by executing dedicated processing software installed in advance on the computer on the computer.
- a characteristic control operation in the LC-MS analysis system of the present embodiment will be described.
- an example will be described in which a specific analysis compound in a large number of specimens requested by a medical institution or the like is quantified at the contract analysis office using this LC-MS analysis system.
- which compound is to be quantified in each specimen is determined by the requesting medical institution or the like. Therefore, sample information indicating the correspondence between the sample number and the name of the analysis target compound (the name of the compound to be quantified) as shown in FIG. Or through a communication line such as the Internet, the data is taken into the control unit 3 of the present system and stored in the sample information storage unit 361 of the storage unit 36.
- one analysis target compound may be set for one specimen, or two or more analysis target compounds may be set.
- the types of specimens such as blood and urine are determined, and the types of compounds to be identified are also determined. Therefore, an administrator who has specialized knowledge of analysis and has high access authority to the system at the contract analysis office analyzes each compound in the sample, and based on the analysis result, The optimal analytical conditions for quantifying compounds are determined experimentally for each compound. Then, an analysis method file describing the analysis conditions is created using the function of the analysis method creation processing unit 31.
- the analysis method creation processing unit 31 stores the analysis method file created by the manager in the analysis method storage unit 362 of the storage unit 36.
- one analytical method is created for one compound, and information indicating the compound, typically a compound name, is included in the analytical method.
- the plurality of compounds may be associated with a single analytical method. Information indicating the plurality of compounds is included in the analytical method.
- the analysis method includes LC separation conditions such as mobile phase flow rate, column temperature, gradient conditions, and the like.
- Retention time which is the time to elute from the column 14, MRM transition suitable for detecting the compound in the tandem quadrupole mass spectrometer 15, and peak for detecting the peak derived from the compound on the extracted ion chromatogram Analysis conditions such as waveform processing conditions, a calibration curve indicating the relationship between the concentration and peak area in the compound, and parameters thereof are included.
- step S1 The operator confirms this list, selects and instructs one or more analysis methods to be used (step S1).
- the method information creation processing unit 32 reads the instructed analysis method file from the analysis method storage unit 362, and extracts information on the compound name described in each analysis method file. And the method information which matched the name (method file name) and compound name of each analysis method is produced, and it stores in the method information storage part 363 of the memory
- FIG. 4 is an example of method information. This method information includes all analysis methods selected and designated by the operator in step S1.
- the method information creation processing unit 32 creates method information for all the analysis methods stored in the analysis method storage unit 362 without the operator instructing the analysis method to be used for analysis in step S1. Also good. In the case where the number of analysis methods stored in the analysis method storage unit 362 is not so large, there is no problem even with such a method. Alternatively, a plurality of analysis methods may be grouped, and all the analysis methods belonging to the instructed group may be selected and instructed by an operator instructing the group. For example, by grouping analysis methods according to the purpose of analysis such as for XX inspection and for ⁇ inspection, it is possible to reduce the burden on the operator and prevent work errors.
- the operator places a vial containing each sample to be analyzed on the sample plate 21 of the autosampler 2, and sets the vial number determined on the sample plate 21 and the sample number for specifying the sample. Correspondence is registered from the input unit 4 (step S3). Specifically, for example, as shown in FIG. 5B, the sample plate 21 has a vial number (in this example, vial numbers 1 to 20), and which sample number corresponds to each vial number. The operator specifies whether to place a new vial. Alternatively, the operator designates in which vial number the sample is placed with respect to the sample number given to each sample to be analyzed. In any case, by such input, as shown in FIG. 5A, sample registration information in which the specimen number and the vial number are associated is obtained.
- vial number in this example, vial numbers 1 to 20
- the use method automatic determination unit 34 refers to the sample information stored in the sample information storage unit 361 and determines the compound name corresponding to each sample number registered in the sample registration information. Investigate. For example, for the sample number “U0001” associated with the vial number “1” in the sample registration information, referring to the sample information shown in FIG. 3, two compound names “C1” and “C2” are displayed. I want. Next, the used method automatic determination unit 34 refers to the method information stored in the method information storage unit 363 and checks the analysis method file name used for the analysis for each compound obtained as described above. For example, referring to the method information shown in FIG. 4 for the compound “C1”, an analysis method whose file name is “Method_M” is obtained.
- An analysis method with the file name “Method_C” is obtained for the compound “C2”.
- two analysis methods “Method_M” and “Method_C” are suitable for analyzing the target compound contained in the sample in the vial placed at the position of the vial number “1” on the sample plate 21. It turns out that.
- an analysis method suitable for analyzing the target compound contained in the specimens in the vials placed at the positions of all the vial numbers is found (step S4).
- step S5 determines whether or not there is no sample associated with the analysis method after the process of step S4 is completed. If Yes in step S5, appropriate analysis or data analysis processing cannot be performed for any sample. Therefore, an error notification is displayed on the display unit 5 (step S6), and the process is terminated. That is, in this case, no analysis is performed.
- step S5 the used method automatic determination unit 34 determines whether there is a compound that does not correspond to the analysis method (step S7). If it is determined No in step S7, an analysis method for performing an appropriate analysis is determined for all target compounds in all samples, and the process proceeds to step S9. On the other hand, if it is determined Yes in step S7, there is no appropriate analysis method for one target compound in at least one sample, and appropriate analysis is performed for one target compound in at least one sample. Means that the method exists. At this time, since the target compound having an appropriate analysis method can be analyzed, a warning notification is displayed on the display unit 5 (step S8), and the process proceeds to step S9.
- step S 9 the analysis schedule creation unit 35 creates an analysis schedule table describing details of each analysis according to the analysis order, and stores the analysis schedule table in the analysis schedule storage unit 364 of the storage unit 36.
- the analysis schedule table includes the vial number, the file name of the analysis method used when analyzing the sample placed in the vial number, the sample collection amount (injection amount into the LC-MS unit 1), etc. Contains information.
- FIG. 6B is an example of a part of the analysis schedule table.
- the first analysis according to the analysis method whose file name is “Method_C” is first performed on the sample in the vial placed at the position of the vial number “1”. Subsequently, the second analysis according to the analysis method whose file name is “Method_M” is performed. Next, the sample in the vial placed at the position of vial number “2” is first subjected to the third analysis according to the analysis method whose file name is “Method_A”, and subsequently the file name The fourth analysis is performed according to the analysis method with “Method_C”.
- Method_A When the analysis in accordance with the analysis method “Method_A” is performed on the sample in the vial placed at the position of the vial number “2”, the number of parameter changes that require time for setting the temperature or the like is minimized. The time and solution can be saved by reducing the number of washings.
- FIG. 6 shows an example of an analysis schedule table when continuous analysis is performed with a brute force formula when there are three analysis methods “Method_A”, “Method_C”, and “Method_M”. Shown in (a).
- the analysis using an analysis method that is not suitable for analyzing a target compound contained in a certain sample is executed, the number of analyzes increases.
- analysis using an analysis method that is not suitable for analyzing a target compound contained in a sample is omitted, so that unnecessary analysis is not performed. Less often.
- an analysis method suitable for the target compound specified in the sample information is automatically selected without bothering the operator, and the analysis schedule table Is created. Therefore, there is no risk of work mistakes by the operator, and continuous analysis can be performed efficiently, and the time required for analysis can be shortened compared to the prior art. Further, useless use of the sample and useless consumption of the mobile phase in the LC-MS unit 1 are eliminated, which is effective in reducing the analysis cost.
- the analysis method includes the retention time during which the target compound elutes from the column 14 under the LC separation conditions described in the analysis method. Included as one of As described above, in many cases, LC separation conditions for different compounds are different, but in some cases, exactly the same LC separation conditions may be defined for a plurality of compounds. In that case, if the retention times for the plurality of compounds do not overlap (in fact, the retention time ranges giving a predetermined time width to the retention times do not overlap), the plurality of compounds are analyzed once. Can be detected.
- the used method automatic determination unit 34 confirms the contents (analysis conditions and parameters thereof) of the plurality of analysis methods instructed to be selected, and when there are a plurality of analysis methods having the same LC separation condition, the plurality of analysis methods are determined.
- the analysis conditions of the analysis methods are merged to create a temporary analysis method with multiple target compounds.
- the temporary analysis is suitable as an analysis method suitable for analyzing the sample. Select a method. According to this, for example, as in the example shown in FIG. 6B, it is necessary to perform two analyzes using different analysis methods on the specimen in the vial given one vial number. There is a possibility that a single analysis using a temporary analysis method may be sufficient. As long as the retention times of a plurality of target compounds do not overlap, each target compound can be detected without affecting each other, and an extracted ion chromatogram corresponding to each target compound can be created. Thereby, it is possible to accurately quantify each target compound.
- the analyzer control device is applied to the LC-MS.
- the present invention is not limited to the LC-MS, but various analyzers such as LC, GC, GC-MS, and others. Can be applied to.
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Abstract
Description
いま、例えば、検体が被検者の血液や尿であって、検体に含まれる既知の薬物や代謝物などを定量するケースを考える。こうした検査では、対象とする化合物の種類は限られているものの、検体毎に定量したい化合物の種類が異なるような場合がよくある。上記従来手法では、最初に選択された分析メソッドを用いた分析が各検体に対してそれぞれ実行される、つまり総当たり的に実行されることになるが、そうなると、或る検体で定量対象となっていない化合物用に作成された分析メソッドを用いた分析が、該検体に対しても実行されることになる。こうした分析は実際には意味がなく、無駄に検体を使用するだけである。また、分析に掛かる時間も無駄であるし、LCやGCでは、移動相やキャリアガスも無駄に消費されることになる。
a)分析対象である検体毎に、該検体に含まれる可能性がある一又は複数の目的化合物を示す検体情報を取得する検体情報取得部と、
b)分析を遂行するための分析条件が記載されている分析メソッド毎に、該分析メソッドに含まれる該分析メソッドを用いた分析で想定されている化合物を示す情報、を取得して、分析メソッドと化合物とを対応付けたメソッド情報を作成するメソッド情報取得部と、
c)一つの検体に対する分析又は複数の検体に対する連続分析に際し、実際にその分析に供される一又は複数の検体がオペレータにより指定されたときに、前記検体情報取得部による検体情報に基づいて、指定された検体のそれぞれにおける目的化合物を特定し、前記メソッド情報取得部によるメソッド情報に基づいてその特定された目的化合物に対応した分析メソッドを特定し、検体とその分析に使用するのに適した分析メソッドとを対応付けた組み合わせの情報を作成する最適メソッド判定部と、
を備え、前記最適メソッド判定部により作成された情報に基づいて、一つの検体に対する分析又は複数の検体に対する連続分析を実行するようにしたことを特徴としている。
そこで、メソッド情報取得部は例えば、一つ又は複数の検体に対する分析に使用される可能性がある分析メソッドが複数指定されたとき、それら分析メソッドに含まれる化合物の情報を読み出し、分析メソッドと化合物との対応を示すメソッド情報を作成する。また、そうした分析メソッドの指定に依らず、作成された又は与えられた全ての分析メソッドについて、分析メソッドと化合物との対応を示すメソッド情報を作成するようにしてもよい。
このLC-MS分析システムは、試料溶液(検体)に含まれる化合物を時間的に分離して検出する液体クロマトグラフ質量分析部(LC-MS部)1、予め用意された多数のバイアル22を一つずつ選択して該バイアル22中の試料溶液をLC-MS部1へと供給するオートサンプラ2、これらの動作を制御する制御部3、などを備える。
ここでは図示しないが、タンデム四重極型質量分析計15は、エレクトロスプレイイオン源などの大気圧イオン源と、大気圧イオン源で生成されたイオンを質量電荷比に応じて分離する前段四重極マスフィルタと、該マスフィルタを通り抜けてきたイオンを衝突誘起解離(CID)などの手法により解離させるコリジョンセルと、該コリジョンセルで解離されて生成したプロダクトイオンを質量電荷比に応じて分離する後段四重極マスフィルタと、該マスフィルタを通り抜けてきたイオンを検出してイオン量に応じた検出信号を出力する検出器と、を有する。
この場合、各検体においていずれの化合物を定量するのかは、依頼元の医療機関等で決定される。そのため、図3に示したような、検体番号と分析対象化合物名(定量したい化合物名)との対応関係を示す検体情報が外部(例えば医療機関)から提供され、この情報が例えば記憶媒体を介して又はインターネット等の通信線を通して、本システムの制御部3に取り込まれ、記憶部36の検体情報記憶部361に格納される。図3に例示したように、一つの検体に一つの分析対象化合物が設定されている場合もあれば、二つ以上の分析対象化合物が設定されている場合もある。
オペレータは分析に際して、例えば管理担当者が作成した指示書などに従い、複数の検体に対する一連の分析に使用する分析メソッドを一又は複数指定する。具体的には、オペレータが入力部4で所定の操作を行うと、その操作を受けてサンプル登録処理部33は、分析メソッド記憶部362に登録されている分析メソッドファイルの一覧を表示部5の画面上に表示する。オペレータはこの一覧を確認し、使用したい一又は複数の分析メソッドを選択して指示する(ステップS1)。この選択指示を受けてメソッド情報作成処理部32は、指示された分析メソッドファイルを分析メソッド記憶部362から読み出し、各分析メソッドファイル中に記述されている化合物名の情報を抽出する。そして、各分析メソッドの名称(メソッドファイル名)と化合物名とを対応付けたメソッド情報を作成し、記憶部36のメソッド情報記憶部363に格納する(ステップS2)。
図4はメソッド情報の一例である。このメソッド情報には、ステップS1でオペレータにより選択指示された全ての分析メソッドが含まれる。
上述したように、図1に示したLC-MS分析システムでは、分析メソッドには、その分析メソッド中に記述されているLC分離条件に下で目的化合物がカラム14から溶出する保持時間が分析条件の一つとして含まれる。上述したように、多くの場合には、異なる化合物に対するLC分離条件はそれぞれ異なるが、場合によっては、複数の化合物に対し全く同じLC分離条件が定められていることがある。その場合、その複数の化合物に対する保持時間が重なっていなければ(実際には保持時間に対して所定の時間幅を与えた保持時間範囲が重なっていなければ)、それら複数の化合物を1回の分析で検出することができる。
11…移動相容器
12…ポンプ
13…インジェクタ
14…カラム
15…タンデム四重極型質量分析計
2…オートサンプラ
21…試料プレート
22…バイアル
23…プレート移動部
24…試料採取部
3…制御部
30…分析制御部
31…分析メソッド作成処理部
32…メソッド情報作成処理部
33…サンプル登録処理部
34…使用メソッド自動判定部
35…分析スケジュール作成部
36…記憶部
361…検体情報記憶部
362…分析メソッド記憶部
363…メソッド情報記憶部
364…分析スケジュール記憶部
4…入力部
5…表示部
Claims (3)
- 一若しくは複数の化合物が含まれる一つの検体に対する分析、又は、複数の前記検体に対する連続的な分析を行う分析装置の動作を制御する分析装置用制御装置であって、
a)分析対象である検体毎に、該検体に含まれる可能性がある一又は複数の目的化合物を示す検体情報を取得する検体情報取得部と、
b)分析を遂行するための分析条件が記載されている分析メソッド毎に、該分析メソッドに含まれる該分析メソッドを用いた分析で想定されている化合物を示す情報、を取得して、分析メソッドと化合物とを対応付けたメソッド情報を作成するメソッド情報取得部と、
c)一つの検体に対する分析又は複数の検体に対する連続分析に際し、実際にその分析に供される一又は複数の検体がオペレータにより指定されたときに、前記検体情報取得部による検体情報に基づいて、指定された検体のそれぞれにおける目的化合物を特定し、前記メソッド情報取得部によるメソッド情報に基づいてその特定された目的化合物に対応した分析メソッドを特定し、検体とその分析に使用するのに適した分析メソッドとを対応付けた組み合わせの情報を作成する最適メソッド判定部と、
を備え、前記最適メソッド判定部により作成された情報に基づいて、一つの検体に対する分析又は複数の検体に対する連続分析を実行するようにしたことを特徴とする分析装置用制御装置。 - 請求項1に記載の分析装置用制御装置であって、
分析対象として指定された1又は複数の検体にそれぞれ含まれる目的化合物の中で、対応する分析メソッドが存在しない目的化合物が少なくとも一つあり、且つ、対応する分析メソッドが存在する目的化合物が少なくとも一つある場合には、該化合物についての分析を実行しつつ警告報知を行う一方、対応する分析メソッドが存在する目的化合物が一つもない場合には、エラー報知を行うことを特徴とする分析装置用制御装置。 - 請求項1又は2に記載の分析装置用制御装置であって、
前記最適メソッド判定部による処理の結果、同一検体に対して複数の分析メソッドが対応付けられている場合、それら複数の分析メソッドにそれぞれ含まれる分析条件の一部が同一であり、同一でない分析条件がそれら複数の分析メソッドに対応している複数の目的化合物の分析結果に影響を及ぼさないことを確認し、その確認ができたときに、その複数の分析メソッドに含まれる分析条件を統合して複数の目的化合物に対応した一時的分析メソッドを作成する分析メソッド統合部をさらに備えることを特徴とする分析装置用制御装置。
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