JP4428077B2 - Automatic analyzer - Google Patents

Description

  The present invention relates to an analyzer such as a liquid chromatograph and a gas chromatograph, and more particularly to an automatic analyzer that sequentially performs analysis while automatically exchanging and selecting a plurality of samples. The automatic analyzer according to the present invention is particularly suitable for an analyzer that requires a relatively long time for, for example, pretreatment of a sample or setting of analysis conditions before starting execution of an analysis operation on the sample.

  For example, in a liquid chromatograph, if a large number of samples are set in the autosampler rack in advance and the operator inputs a schedule table that defines the analysis order, analysis conditions, etc. of the samples, the analysis start is instructed. Samples are sequentially selected according to the schedule table, and the analysis is automatically executed under the set analysis conditions (see, for example, Patent Document 1). In such a continuous automatic analysis for a large number of samples, it takes time to complete the entire analysis, so in general, during the automatic analysis, the operator has to leave the device and perform other work or away from the installation location of the device. I often go to places.

  If the time required for analysis or the end time of analysis is known in advance before the start of continuous analysis, the operator will return to the device before and after the end time, and replace the sample without analysis after the end of analysis. Operations such as restarting and processing analysis results can be performed efficiently. For this purpose, there is conventionally known an apparatus that estimates the time required for analysis and the analysis end time before starting the continuous analysis or for each analysis and displays the estimated time on the display screen. However, in the conventional apparatus, the accuracy of the estimation of the analysis required time and the analysis end time is not necessarily high, and the actual analysis required time and the analysis end time may deviate significantly from the estimated values. The main causes of such a large time error are as follows.

That is, in general, in an automatic analyzer, even if a control unit issues a start command for each analysis according to a schedule table, an analysis operation for a sample is not actually executed immediately. Taking a liquid chromatograph as an example, in a liquid chromatograph, an autosampler (sample injection device) starts an operation to select and collect a specified sample in response to an analysis start command. Pretreatments such as concentration, dilution, and mixing may be performed, and such treatment takes some time. In addition, the column oven that has received the analysis start command executes temperature rise or temperature fall control so that the inside of the oven tank has a temperature set as one of the analysis conditions. Accordingly, the time from when an analysis start command is issued in one analysis to the actual start of analysis (hereinafter referred to as pre-analysis preparation time) is the time during which the analysis operation is actually performed on the sample. Compared to (hereinafter referred to as analysis time), it is too long to be ignored. Therefore, in the conventional apparatus, when a certain fixed value Ta is used as the preparation time before analysis, for example, when the analysis time in each analysis is all Tb when performing the analysis N times in total, The time required for analysis Ttotal is estimated by the following equation.
Ttotal = N × (Ta + Tb)

  The analysis time for each analysis is determined by the operator, and is set as one of the analysis conditions in the schedule table, so that an accurate value can be extracted from the schedule table. However, the pre-analysis preparation time is not inherently constant. Depending on the presence or absence of sample pretreatment as described above, or when trying to perform a certain analysis, the analysis conditions from the analysis conditions immediately before the analysis are analyzed. It may vary depending on whether there is any change. For example, when a certain analysis is performed, if the column oven temperature is the same as the column oven temperature in the immediately preceding analysis, there is no need to raise or lower the temperature, and the preparation time before the analysis is short, but the column in the immediately preceding analysis is short. When the column oven temperature is different from the oven temperature, it takes time to raise or lower the temperature, and the waiting time until the temperature stabilizes is added, and the pre-analysis preparation time becomes longer. In the conventional automatic analyzer, when the analysis required time is calculated, the fluctuation factor of the pre-analysis preparation time is not considered at all, and the estimation of the analysis required time may be largely deviated.

Japanese Patent Laid-Open No. 10-318803 (FIG. 2 and paragraphs 0017 to 0019)

  The present invention has been made in view of such problems, and an object of the present invention is to perform analysis before or during execution of continuous analysis in an automatic analyzer that continuously performs analysis on a plurality of samples. An object of the present invention is to provide an automatic analyzer capable of improving accuracy of estimation of time and analysis end time and presenting accurate information by an operator (analyst).

In order to solve the above-described problems, the present invention is an automatic analysis in which samples are sequentially exchanged and selected according to a schedule table set in advance and analysis conditions are set for each of the samples to continuously execute analysis of a plurality of samples. In an automatic analyzer that estimates the required time or scheduled end time of continuous analysis before the start of continuous analysis or during the execution of continuous analysis,
when running a) continuous analysis, and time measuring means for measuring the pre-analysis preparation time up to the point of ready actually analyzing the analysis from the point of analysis start instruction has been issued in each analysis is started,
b) The measured value data of the pre-analysis preparation time by the time measuring means includes information indicating the transition state from the analysis condition in the immediately preceding analysis to the analysis condition in the analysis, which affects the length of the pre-analysis preparation time. Storage means for storing in association with parameters;
c) Refer to the storage means when estimating the time required for the continuous analysis or the scheduled end time, and for the analysis under the same parameter as the parameter for which the actual measurement value data of the pre-analysis preparation time exists, both the use of value data, the use of a specified value for analysis under the parameters measured value data of the pre-analysis preparation time is not present, the required in one analysis by adding the time required to perform the actual analysis to An arithmetic processing means for calculating the time, calculating the total time required for each analysis until the final analysis according to the schedule table, and estimating the time required for the continuous analysis;
It is characterized by having.

Since the work and processing to be performed within the “preparation time before analysis” vary depending on the type of analyzer, etc., the “parameters affecting the length of preparation time before analysis” also vary depending on the type of analyzer, etc. is there. Generally, when environmental conditions such as temperature and humidity are one of the analysis conditions, it takes time to change and stabilize these environmental conditions. Therefore, whether the analysis conditions are the same in two consecutive analyzes or whether the analysis conditions need to be changed greatly affects the length of preparation time before analysis. Therefore, in the automatic analyzer according to the present invention, as the parameter for a certain analysis, and information indicating the transition state from the analysis conditions in the immediately preceding analysis to the analysis conditions in the analysis including useless. Since the analysis conditions are described in the schedule table, the transition state of the analysis conditions can be grasped from the description of the schedule table.

  In the automatic analyzer according to the present invention, the time measuring means measures the pre-analysis preparation time in the process of continuously analyzing a plurality of samples according to the schedule table. The actually measured value data of the pre-analysis preparation time obtained in this way is stored in the storage means in association with a parameter that affects the length of the pre-analysis preparation time, for example, the transition state of the analysis conditions described above. For example, when there are three types of analysis conditions A, B, and C, the transition conditions of analysis conditions are A → A, A → B, A → C, B → A, B → B, B →. Nine ways of C, C → A, C → B, and C → C are conceivable. That is, the pre-analysis preparation time is different for each of the nine transition states (which may of course be the same by chance). Conversely, if the transition states are the same, the pre-analysis preparation time is almost the same. That's it. Therefore, the arithmetic processing unit refers to the storage content of the storage unit when estimating the time required for the continuous analysis or the scheduled end time.

  That is, when calculating the time required for any one analysis described in the schedule table, the transition state of the analysis condition in the analysis (that is, the transition state from the analysis state in the immediately previous analysis to the analysis condition in the analysis) ) And referring to the storage means to check whether there is pre-analysis preparation time actual measurement value data corresponding to the transition state. If the actual measurement data exists, the data is extracted and used as the pre-analysis preparation time. If the actual measurement data does not exist, the predetermined specified value is adopted as the pre-analysis preparation time. Then, the analysis time described as one of the analysis conditions is added to the pre-analysis preparation time to determine the required time for the one analysis. When calculating the time required for analysis before the start of continuous analysis, calculate the time required for each analysis as described above for all the analyzes described in the schedule table, and calculate the total sum to calculate the continuous time. Get time required for analysis. On the other hand, when calculating the remaining analysis time during the execution of continuous analysis, each of the analyzes that have not yet been analyzed among all the analysis described in the schedule table is performed as described above. The time required for analysis is calculated, and the total time is calculated to obtain the time required for analysis (more precisely, the remaining required time).

  Therefore, if there is no or very little pre-analysis preparation time actual measurement data in the storage means, a specified value with poor accuracy is adopted as the pre-analysis preparation time when calculating the time required for analysis. However, if the measurement preparation data before analysis in the storage means is enriched, there is a high probability that accurate measurement data will be adopted as the preparation time before analysis when calculating the time required for analysis. . Thereby, the estimation accuracy of the time required for the continuous analysis can be improved, and the accuracy is also increased when the scheduled analysis end time is presented based on this. When calculating the required analysis time before the start of continuous analysis, it is possible to use the actual measurement data measured during the continuous analysis performed in the past. In addition to the actual measurement data measured during the continuous analysis performed in the past, the actual measurement data measured in the analysis that has already been completed in the continuous analysis currently performed is also calculated. Can be used. Therefore, in the latter case, the calculation accuracy of the time required for analysis improves as the analysis progresses in the continuous analysis.

  In view of the gist of the present invention as described above, the present invention is particularly effective for an analysis apparatus in which the pre-analysis preparation time is relatively long and the length of time varies greatly depending on the analysis conditions and the like. is there. The most typical of such analyzers is a chromatographic analyzer that separates each component contained in a sample with a column in time and detects each separated component sequentially, specifically a liquid chromatograph or gas chromatograph. Graph. Therefore, by applying the present invention to the chromatographic analyzer, the calculation accuracy of the time required for analysis can be greatly improved compared to the conventional case.

  According to the automatic analyzer according to the present invention, when the time required for continuous analysis or the scheduled end time of analysis is presented to the operator before the start of continuous analysis or during the execution of continuous analysis, the calculation accuracy of the time is compared with the conventional one. Can be improved. Therefore, for example, when an operator who has been away from the apparatus during the continuous analysis returns to the apparatus with reference to the information presented as described above, it is highly likely that it is immediately before or after the end of the continuous analysis. The work can be efficiently performed without wasting time.

Hereinafter, a liquid chromatograph as an embodiment of an automatic analyzer according to the present invention will be described with reference to the drawings.
FIG. 1 is a block diagram of the main part of a liquid chromatograph according to this embodiment. This liquid chromatograph includes an eluent (mobile phase) tank 1, a liquid feed pump 2, an autosampler 3, a column 6 built in a column oven 5, a detector 7, and a control unit 8 and a control unit for controlling these units, respectively. 8 includes a personal computer 9 that manages analysis work through 8 and analyzes and processes data obtained by the detector 7.

  The analysis operation by the liquid chromatograph will be schematically described. Under the control of the control unit 8 which receives an instruction from the personal computer 9, the liquid feed pump 2 supplies the eluent sucked from the eluent tank 1 at a substantially constant flow rate. Therefore, it flows to the column 6 through the autosampler 3. The autosampler 3 has a rack 4 on which a large number of sample bottles (vials) are mounted. A predetermined sample is selected under the control of the control unit 8 and injected into the eluent at a predetermined timing. To do. This sample is introduced into the column 6 on the eluent. Since each component in the sample passes through the column 6 (retention time) varies depending on the component, each component in the sample is temporally separated while passing through the column 6. The detector 7 sequentially detects the components separated and eluted by the column 6 in this way, and sends detection data to the personal computer 9 via the control unit 8. The personal computer 9 stores the received data in a storage device such as a hard disk, and performs predetermined processing to create a chromatogram and display it on the screen of the display 11.

  In order to continuously analyze a large number of samples mounted on the rack 4, the operator sets a schedule table from the input unit 10 prior to analysis. FIG. 2 is an example of this schedule table. The analysis method is the name of the data file describing the analysis conditions. Therefore, when the analysis method is the same, the analysis conditions are exactly the same. Examples of the analysis conditions include a set temperature of the column oven 5, a sample injection condition by the autosampler 3, and an analysis time. Here, it is assumed that the column oven set temperature is 40 ° C. for Method_1 and 60 ° C. for Method_2.

  The operator gives an instruction to start continuous analysis after setting the schedule table as shown in FIG. Upon receiving an instruction to start continuous analysis, the personal computer 9 sends analysis condition data to the control unit 8 in the order of the schedule table, and instructs the start of analysis. Further, the personal computer 9 estimates the time required for all analyzes described in the schedule table, and displays, for example, the scheduled end time of analysis on the screen of the display 11. The procedure for estimating the total analysis time, which is a feature of the liquid chromatograph of this embodiment, will be described below.

In this liquid chromatograph, the pre-analysis preparation time is measured for each analysis in the course of executing continuous analysis, and the measured value data is stored as a table in association with the transition state of the analysis method (that is, analysis conditions). Considering the example of FIG. 2 now, the following four patterns can be considered in the transition state of the analysis method.
[i] Method_1 → Method_1
[ii] Method_1 → Method_2
[iii] Method_2 → Method_1
[iv] Method_2 → Method_2
In [i], the column oven temperature is maintained at 40 ° C., and in [iv], the column oven temperature is maintained at 60 ° C. In any case, since the temperature increase or decrease control in the column oven 5 is unnecessary, the pre-analysis preparation time is relatively short. In contrast, in [ii], it is necessary to control the temperature of the column oven from 40 ° C to 60 ° C. In [iii], it is necessary to control the temperature of the column oven from 60 ° C to 40 ° C. The time is relatively long (actually it takes several minutes). Since the pre-analysis preparation times for these four transition states are different (they may coincide by chance), actual measurement data of the pre-analysis preparation times for these four transition states should be acquired during the analysis execution process. Is desirable. That is, in the case of the above example, the actual value table of the pre-analysis preparation time is as shown in FIG.

In order to create such an actual measurement value table, the personal computer 9 specifically executes the processing shown in FIG. 3 in each analysis. First, the transition state from the analysis method in the immediately previous analysis to the current analysis method is extracted from the schedule table (step S10). Next, it is determined whether or not the transition state or the actually measured value data corresponding thereto exists in the pre-analysis preparation time actually measured value table (step S11). If the transition state or the actually measured value data corresponding to the transition state exists in the actually measured value table, it is not necessary to actually measure the pre-analysis preparation time, and the process is terminated as it is.

  On the other hand, when the transition state or the actual measurement data corresponding thereto does not exist in the actual measurement value table, the time from when the analysis start command is issued until the actual analysis operation for the sample is started, that is, the pre-analysis preparation time Is actually measured (step S12). In the case of a liquid chromatograph, the start of the analysis operation on the sample is the sample injection time when the sample solution is injected into the eluent by the autosampler 3, and a signal notifying that the sample is actually injected is controlled from the autosampler 3. The data is transmitted to the personal computer 9 via the unit 8. When the actual measurement data is obtained, the actual measurement data is stored in the actual measurement value table in association with the transition state of the analysis method (step S13). Even if it is determined in step S11 that the actual measurement value data already exists in the actual measurement value table, the process proceeds to steps S12 and S13 to actually measure the pre-analysis preparation time and rewrite the already written actual measurement value. You may do it.

  Since the above processing is executed for each analysis, when there are various transition state patterns for the analysis method, the contents of the pre-analysis preparation time actual measurement value table are enriched as the analysis progresses, that is, the actual measurement value data is Transition states that do not exist decrease. In the continuous analysis according to the schedule table of FIG. 2, assuming that the state before the start of analysis is the analysis method Method_1, when the analysis of number = 1, for the transition state of [ii] (Method_1 → Method_2) The actual measurement value of the pre-analysis preparation time is measured, and the actual measurement value data t2 is stored in association with Method_1 → Method_2 on the actual measurement value table. Next, in the analysis of number = 2, the measured value of the preparation time before analysis for the transition state of [iv] (Method_2 → Method_2) is measured, and in the measured value table, Method_2 → Method_2. The actual measurement data t4 is stored in association with each other, and the actual measurement data t3 is stored in association with Method_2 → Method_1 on the actual measurement value table in the same manner for the subsequent analysis of number = 3.

  Thereafter, for the numbers 4 to 10, if the actual measurement value data already exists in the actual measurement value table, the pre-analysis preparation time is not actually measured during this period. Then, in the analysis of number = 11, the measured value of the pre-analysis preparation time for the transition state of [i] (Method_1 → Method_1) is measured, and in the measured value table, it corresponds to Method_1 → Method_1. Measured value data t1 is stored. For the first time at this point, actual measurement data for all transition states shown in FIG. 4 is stored.

  When the calculation of the time required for continuous analysis is instructed, the personal computer 9 executes arithmetic processing according to the procedure shown in FIG.

  First, in accordance with the numerical order described in the schedule table (FIG. 2), the transition state from the analysis method in the immediately previous analysis to the current analysis method is extracted from the schedule table for one analysis (step S20). Next, it is determined whether or not the actual measurement value data corresponding to this transition state exists in the pre-analysis preparation time actual measurement value table (step S21). If actual measurement data corresponding to the transition state exists in the pre-analysis preparation time actual measurement value table, the actual measurement data associated with the transition state in the table is read as the pre-analysis preparation time ( On the other hand, if the actual measurement data corresponding to the transition state does not exist in the pre-analysis preparation time actual measurement value table, a predetermined default value t0 is set as the pre-analysis preparation time (step S23). In either case, the analysis time is included as one of the analysis conditions defined by the analysis method, so this analysis time and the previous pre-analysis preparation time are added to obtain the required time for that one analysis. (Step S24).

  Next, it is determined whether or not the calculation of individual required times for all analyzes has been completed on the schedule table, and if there is an incomplete one, the process returns to step S20. Accordingly, the time required for each analysis is calculated in the order of the numbers described in the schedule table, and when the time required for the analysis at the bottom line (number = 12 in the example of FIG. 2) is calculated, the process proceeds from step S25 to S26. Proceed with Then, the sum of the individual required times of all the analyzes calculated so far is calculated, and this is set as the required time for the continuous analysis, and then the scheduled analysis end time is further calculated (step S26).

  As described above, the process for calculating the time required for the continuous analysis may be performed before the start of the continuous analysis or may be performed before the start of any analysis during the execution of the continuous analysis. Specifically, when the continuous analysis according to FIG. 2 is executed from the state in which the pre-analysis preparation time actual measurement value table is not created before the start of the continuous analysis, the following is performed.

  When an instruction is given to calculate the time required for analysis before the start of the continuous analysis, there is no actual measurement data, and therefore, in the flowchart in FIG. The default value t0 is adopted as the pre-analysis preparation time. Accordingly, the accuracy of the time required for analysis at this time is not so high.

  Next, consider the case of calculating the time required for analysis at the end of the analysis of number = 1. At this time, only the actual measurement data t2 corresponding to the transition state of Method_1 → Method_2 is stored in the actual measurement table by the actual measurement processing of the pre-analysis preparation time as described above. Therefore, for the analysis in which the transition from Method_1 to Method_2 in the analysis after number = 2, it is possible to adopt actually measured value data instead of the default value as the preparation time before analysis. Specifically, as shown in FIG. 2, for example, analysis of number = 4 is the case. Therefore, for the analysis of this number = 4, the pre-analysis preparation time is accurate, so the time required for this single analysis can be accurately obtained. For other analyses, the default value must be adopted as the pre-analysis preparation time, but the accuracy of the scheduled end time of the analysis is definitely improved over that obtained before the start of the continuous analysis.

  Further, consider the case where the time required for analysis is calculated at the end of the analysis of number = 2. At this time, actually measured value data t4 corresponding to the transition state of Method_2 → Method_2 is additionally stored in the actually measured value table. Therefore, in the analysis after number = 3, not only the transition state of Method_1 → Method_2 but also the transition state of Method_2 → Method_2 can adopt measured value data instead of the default value as the preparation time before analysis. Specifically, as shown in FIG. 2, for example, analysis of number = 5 is the case. Therefore, for the analysis of numbers = 4 and 5, since the pre-analysis preparation time is accurate, the time required for these two analyzes can be accurately obtained. That is, since the number of cases where the actual measurement data is employed as the pre-analysis preparation time is further increased than in the above case, the accuracy of the scheduled analysis end time is further improved. Similarly, as the analysis progresses and the actual measurement data on the actual measurement table is enriched, the calculation accuracy of the time required for analysis of the unexecuted portion in the schedule table is further improved.

  In the above description, it is assumed that an actual measurement value table for preparatory analysis preparation time has not been created prior to the execution of continuous analysis. However, it is also possible to use actual measurement data actually measured in a continuous analysis performed previously. It is. In this way, the time required for analysis can be calculated with high accuracy even before the start of continuous analysis. However, if they are not within the same continuous analysis, for example, depending on conditions such as ambient temperature, the pre-analysis preparation time is not necessarily the same even if the transition state of the analysis method is the same. However, even in such a case, it is certain that the accuracy of the time required for analysis is remarkably improved as compared with the case where the default value is adopted as the pre-analysis preparation time.

  Moreover, it can be considered that the pre-analysis preparation time varies not only depending on the analysis method (analysis condition) but also other items generally described in the schedule table. For example, in the example of FIG. 2, two racks with numbers 1 and 2 are used as racks, but extra time may be required for rack replacement as the rack number changes. This is the case, for example, when the rack itself is replaced by a rack changer or the like. In such a case, apart from the transition state of the analysis method, the measured value data of the pre-analysis preparation time at the time of the rack number transition is stored in, for example, a table format, and the contents of this table are also referred to as described above. However, it is advisable to make the preparation time before analysis more accurate. Furthermore, as described above, when an item that is not described in the schedule table such as the ambient temperature becomes a variation factor of the pre-analysis preparation time, a table for storing actually measured value data corresponding thereto is prepared. As a result, the accuracy can be further improved.

  Since the above embodiment is merely an embodiment of the present invention, in addition to the above-described variations, it is included in the present invention even if appropriate changes, modifications and additions are made within the scope of the present invention. it is obvious.

The block block diagram of the liquid chromatograph which is one Example of this invention. The figure which shows an example of the analysis schedule table set when performing a continuous analysis. The flowchart which shows the processing operation for creating the preparation time actual measurement value table before analysis in the liquid chromatograph of a present Example. The figure which shows an example of the pre-analysis preparation time actual value table. The flowchart which shows the processing operation for estimating the analysis required time and the analysis completion scheduled time in the liquid chromatograph of a present Example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Eluent tank 2 ... Liquid feed pump 3 ... Autosampler 4 ... Rack 5 ... Column oven 6 ... Column 7 ... Detector 8 ... Control part 9 ... Personal computer 10 ... Input part 11 ... Display

Claims (2)

This is an automatic analyzer that sequentially exchanges and selects samples according to a schedule table that is set in advance and sets analysis conditions for each sample to continuously execute analysis of multiple samples. In the automatic analyzer that estimates and presents the time required for continuous analysis or the scheduled end time during execution,
when running a) continuous analysis, and time measuring means for measuring the pre-analysis preparation time up to the point of ready actually analyzing the analysis from the point of analysis start instruction has been issued in each analysis is started,
b) The measured value data of the pre-analysis preparation time by the time measuring means includes information indicating the transition state from the analysis condition in the immediately preceding analysis to the analysis condition in the analysis, which affects the length of the pre-analysis preparation time. Storage means for storing in association with parameters;
c) Refer to the storage means when estimating the time required for the continuous analysis or the scheduled end time, and for the analysis under the same parameter as the parameter for which the actual measurement value data of the pre-analysis preparation time exists, both the use of value data, the use of a specified value for analysis under the parameters measured value data of the pre-analysis preparation time is not present, the required in one analysis by adding the time required to perform the actual analysis to An arithmetic processing means for calculating the time, calculating the total time required for each analysis until the final analysis according to the schedule table, and estimating the time required for the continuous analysis;
An automatic analyzer characterized by comprising. 2. The automatic analyzer according to claim 1, wherein each component contained in the sample is temporally separated by a column, and chromatographic analysis is performed to sequentially detect the separated components.

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