WO2018142600A1

WO2018142600A1 - Analysis system, analysis method, and analysis control program

Info

Publication number: WO2018142600A1
Application number: PCT/JP2017/004123
Authority: WO
Inventors: 山本　浩平
Original assignee: 株式会社島津製作所
Priority date: 2017-02-03
Filing date: 2017-02-03
Publication date: 2018-08-09
Also published as: JPWO2018142600A1; JP6773138B2

Abstract

A standard specimen measurement process unit 422 executes a standard specimen measurement process for measuring a standard specimen in an LCMS 3. After the process executed by the standard specimen measurement process unit 422, a preprocess executing unit 411 causes a medium specimen to be automatically conveyed from a culturing device 1 to a preprocessing device 2, and causes the preprocessing device 2 to perform a preprocess. A liquid delivery process unit 412 automatically delivers the preprocessed liquid medium specimen to the LCMS 3, and causes the LCMS to perform an analysis. A control unit 4 automatically repeats the processes performed by the preprocess executing unit 411 and the liquid delivery process unit 412 upon a plurality of medium specimens, followed by executing the standard specimen measurement process in the LCMS 3 post-analysis.

Description

Analysis system, analysis method, and analysis control program

The present invention relates to an analysis system, an analysis method, and an analysis control program for analyzing a plurality of medium samples carried out from a culture apparatus.

Conventionally, in order to evaluate the differentiation state of a cell, a method using immunostaining (see, for example, Patent Document 1) or a method for quantifying the expression level of a marker gene (see, for example, Patent Document 2) has been widely used. Yes.

In the method using immunostaining, cells to be evaluated, such as pluripotent stem cells, are first fixed with paraformaldehyde and the antigen-antibody reaction is performed. Here, SSEA-4 and TRA1-60 are widely used as antibodies for determining whether pluripotent stem cells are in an undifferentiated state (see, for example, Patent Document 1). Subsequently, a secondary antibody that binds to the antibody is added to the cells, and then a fluorescent label or the like previously imparted to the secondary antibody is detected. This makes it possible to evaluate whether or not an antigen for the antibody exists on the cell, that is, whether or not the cell is in an undifferentiated state.

In the method of quantifying the expression level of the marker gene, for example, mRNA is extracted from pluripotent stem cells, converted into cDNA by reverse transcriptase, and then the marker gene is obtained by PCR (Polymerase Chain Reaction, polymerase chain reaction). Amplify. At this time, NANOG and POU5F1 (OCT3 / 4) are widely used as marker genes for evaluating the undifferentiation of pluripotent stem cells (see, for example, Non-Patent Document 1). The PCR product is detected by electrophoresis or a real-time PCR apparatus to confirm the expression level of the marker gene in the cell, and from the result, it is evaluated whether or not the cell is in an undifferentiated state.

JP 2004-313184 A JP 2006-042663 A

When evaluating the differentiation state of a cell, after the test cell is cultured in a medium, the cultured sample (medium sample) may be introduced from the culture apparatus into a liquid chromatograph mass spectrometer (LCMS). is there. The medium sample is introduced into LCMS after pretreatment such as deproteinization in a pretreatment apparatus, for example.

Conventionally, the operation of introducing the culture medium sample from the culture apparatus to the pretreatment apparatus and the operation of introducing the pretreated medium sample from the pretreatment apparatus to the LCMS are manually performed by the operator. When analyzing the above, the work was complicated. In particular, in LCMS, for the purpose of maintaining stability of analysis results, it is necessary to perform a stabilization process for stabilizing LCMS, a standard sample measurement process for measuring a standard sample in order to create a calibration curve, and the like. . Therefore, it is necessary to perform a pretreatment of the culture medium sample after performing these treatments, and to introduce the pretreated medium sample into the LCMS, which further complicates the operator's work.

The present invention has been made in view of the above points, and an object of the present invention is to provide an analysis system and an analysis that can perform an analysis efficiently and accurately without requiring the operator to perform complicated operations. A method and an analysis control program are provided.

The cell differentiation state analysis system according to the present invention is an analysis system for analyzing a plurality of medium samples carried out of a culture device, and includes a pretreatment device, a mass spectrometer, and a control unit. The pretreatment apparatus sequentially performs pretreatment on a plurality of medium samples. The mass spectrometer sequentially analyzes each culture medium sample pretreated by the pretreatment device. The control unit controls the pretreatment device and the mass spectrometer.

The control unit includes a standard sample measurement processing unit, a preprocessing execution unit, and a liquid feeding processing unit. The standard sample measurement processing unit executes a standard sample measurement process for measuring a standard sample in the mass spectrometer. The pre-processing execution unit automatically loads a culture medium sample from the culture device to the pre-processing device after the processing by the standard sample measurement processing unit, and causes the pre-processing device to perform pre-processing. The liquid feeding processing unit automatically feeds the pretreated medium sample to the mass spectrometer, and causes the mass spectrometer to perform analysis. The controller performs the standard sample measurement process in the mass spectrometer after the analysis after automatically performing the processing by the pretreatment execution unit and the liquid feeding processing unit repeatedly on a plurality of medium samples. .

According to such a configuration, the standard sample measurement process in the mass spectrometer, the transfer of the medium sample from the culture apparatus to the pretreatment apparatus, and the transfer of the medium sample after the pretreatment from the pretreatment apparatus to the mass analysis apparatus Is done automatically. Furthermore, after pre-processing and analysis for a plurality of medium samples are automatically performed repeatedly, standard sample measurement processing in the mass spectrometer is automatically performed again. Accordingly, the standard sample measurement process is automatically performed before and after the pretreatment and analysis for a plurality of medium samples, and the accuracy of the analysis result can be prevented from being deteriorated due to the change with time. Therefore, it is not necessary for the operator to perform complicated work, and the analysis can be performed efficiently and accurately.

When the number of the plurality of medium samples carried out from the culture apparatus is less than a predetermined number of samples, the standard sample measurement process in the mass spectrometer after analysis may be omitted.

According to such a configuration, when the number of medium samples is relatively small, the standard sample measurement process in the mass spectrometer after the analysis is omitted, so that the analysis time can be shortened and the analysis is accompanied. The consumption of consumables can be reduced. When the number of medium samples is relatively small, the accuracy of the analysis result is hardly lowered due to a change with time, so that the analysis can be performed with high accuracy even if the standard sample measurement process in the mass spectrometer after the analysis is omitted.

When the storage period of a plurality of medium samples carried out from the culture apparatus is less than a predetermined period, the standard sample measurement process in the mass spectrometer after analysis may be omitted.

According to such a configuration, when the storage period of the medium sample is relatively short, the standard sample measurement process in the mass spectrometer after the analysis is omitted, so that the analysis time can be shortened and the analysis can be performed. It is possible to reduce the consumption of consumables. If the storage period of the culture medium sample is relatively short, it is necessary to evaluate the culture medium sample in a short time after feeding. Therefore, it is possible to perform analysis accurately by omitting the standard sample measurement process in the mass spectrometer after analysis. it can.

The control unit may further include a stabilization processing unit that executes a stabilization process for stabilizing the mass spectrometer. In this case, the pretreatment execution unit automatically carries the medium sample from the culture device to the pretreatment device after the processing by the stabilization processing unit and the standard sample measurement processing unit, Processing may be performed.

The analysis system may further include a liquid chromatograph having a column into which the medium sample is introduced and separating each component in the medium sample in the process of passing through the column. In this case, the mass spectrometer may perform mass spectrometry on each component separated in the liquid chromatograph.

The analysis method according to the present invention is a method for sequentially performing a pretreatment on a plurality of medium samples carried out of a culture apparatus by a pretreatment apparatus, and sequentially analyzing each medium sample on which the pretreatment has been performed by a mass spectrometer. An analysis method, which includes a standard sample measurement processing step, a preprocessing execution step, and a liquid feeding processing step. In the standard sample measurement process step, a standard sample measurement process for causing the mass spectrometer to measure a standard sample is executed. In the preprocessing execution step, after the processing in the standard sample measurement processing step, a culture medium sample is automatically carried from the culture device to the pretreatment device, and the pretreatment device performs preprocessing. In the liquid feeding step, the pretreated medium sample is automatically fed to the mass spectrometer, and the mass spectrometer is analyzed. After the processing in the preprocessing execution step and the liquid feeding processing step is automatically repeated on a plurality of medium samples, the standard sample measurement processing is executed in the mass spectrometer after analysis.

The analysis control program according to the present invention sequentially performs pretreatment on a plurality of medium samples carried out from a culture apparatus by a pretreatment apparatus, and sequentially analyzes each medium sample on which pretreatment has been performed by a mass spectrometer. The computer program executes the standard sample measurement processing step, the pre-processing execution step, and the liquid feeding processing step, and performs a plurality of processes by the pre-processing executing step and the liquid feeding processing step. Then, the standard sample measurement process is executed in the mass spectrometer after the analysis.

According to the present invention, since the standard sample measurement process is automatically performed before and after the pretreatment and analysis for a plurality of medium samples, it is possible to prevent the accuracy of the analysis result from being deteriorated due to a change over time. There is no need to perform complicated work, and analysis can be performed efficiently and accurately.

It is a block diagram showing an example of composition of an analysis system concerning one embodiment of the present invention. It is the flowchart which showed the flow at the time of analyzing using the analysis system of FIG. It is the flowchart which showed the 1st modification of the process at the time of an analysis. It is the flowchart which showed the 2nd modification of the process at the time of an analysis.

FIG. 1 is a block diagram showing a configuration example of an analysis system according to an embodiment of the present invention. The analysis system includes a culture apparatus 1, a pretreatment apparatus 2, an LCMS (liquid chromatograph mass spectrometer) 3, a control unit 4, and the like. The culture apparatus 1 sequentially carries out a plurality of medium samples, and the pretreatment apparatus 2 sequentially performs pretreatment on these medium samples. Then, each culture medium sample pretreated by the pretreatment device 2 is sequentially analyzed by the LCMS 3.

The culture apparatus 1 is an apparatus for culturing test cells. As test cells, stem cells, typically pluripotent stem cells such as ES cells and iPS cells, can be used. In addition, cells that have been induced to differentiate from the stem cells can also be used as test cells. As a medium used for culturing such test cells, a medium generally used for culturing stem cells, for example, DMEM / F12 or a medium mainly composed of DMEM / F12 (mTeSR1 or the like) can be used. .

In this embodiment, in order to evaluate the differentiation state of the test cell based on the abundance of the biomarker in the culture supernatant, the culture supernatant (medium sample) is transferred from the culture device 1 to the LCMS 3 via the pretreatment device 2. be introduced. As the biomarker, for example, at least one compound selected from the group consisting of putrescine, kynurenine, cystathionine, ascorbic acid, riboflavin, pyruvate, serine, cysteine, threonic acid, citric acid and orotic acid is used.

The pretreatment device 2 performs a pretreatment such as deproteinization on the culture medium sample automatically and sequentially carried from the culture device 1. Specifically, isopropyl malic acid as an internal standard sample is added to a culture medium sample and treated with an extraction solution. As the extraction solution, for example, a solution in which methanol, chloroform, and water are mixed at a ratio of 2.5: 1: 1 is used. However, the pretreatment is not limited to deproteinization, and other pretreatments may be performed on the medium sample.

The LCMS 3 analyzes the diluted medium sample after adding ultrapure water and diluting the pretreated medium sample automatically and sequentially sent from the pretreatment apparatus 2. The LCMS 3 includes an LC unit and an MS unit (both not shown), and the medium sample is introduced into the column of the LC unit (liquid chromatograph) so that the medium sample in the process of passing through the column. Each component is separated, and mass spectrometry in the MS unit (mass spectrometer) is performed on each separated component.

The control unit 4 includes, for example, a preprocessing control unit 41 and an LCMS control unit 42. The pretreatment control unit 41 includes, for example, a CPU (Central Processing Unit) and executes a program for controlling the culture apparatus 1 and the pretreatment apparatus 2. The LCMS control unit 42 also includes a CPU, controls the operation of the LCMS 3, and receives analysis data from the LCMS 3.

The preprocessing control unit 41 functions as a preprocessing execution unit 411, a liquid feeding processing unit 412, a cleaning processing unit 413, and the like when the CPU executes a program. The pretreatment execution unit 411 controls the operations of the culture apparatus 1 and the pretreatment apparatus 2 to automatically carry the medium sample from the culture apparatus 1 to the pretreatment apparatus 2, and the pretreatment apparatus 2 converts the medium sample into the medium sample. Perform pre-processing. When carrying a culture medium sample from the culture apparatus 1 to the pretreatment apparatus 2, first, the medium is fed to the flow path from the culture apparatus 1 to the pretreatment apparatus 2, and then the co-washing is performed. A medium sample is fed through the flow path.

The liquid feeding processing unit 412 automatically feeds the pretreated medium sample from the pretreatment device 2 to the LCMS 3 by controlling the operation of a pump (not shown), for example. Thereby, the culture medium sample after pre-processing is automatically analyzed in LCMS3.

The cleaning processing unit 413 passes the culture medium sample from the culture apparatus 1 to the pretreatment apparatus 2 and then supplies the next culture medium sample to the flow path from the culture apparatus 1 to the pretreatment apparatus 2. The flow path is cleaned (line cleaning) by supplying the cleaning liquid. In addition, the cleaning processing unit 413 performs the pre-treatment after the medium sample that has been pre-processed by the pre-processing apparatus 2 is supplied to the LCMS 3 and before the next medium sample is supplied to the pre-processing apparatus 2. The flow path of the culture medium sample in the processing apparatus 2 is washed with a washing liquid.

The LCMS control unit 42 functions as a stabilization processing unit 421, a standard sample measurement processing unit 422, an analysis processing unit 423, and the like when the CPU executes a program. The stabilization processing unit 421 executes a stabilization process for stabilizing the LCMS 3. The stabilization process includes, for example, a process of flowing water through the flow path of the culture medium sample in LCMS3 (water hammering) and a process of measuring the background without sending the culture medium sample to LCMS3 (empty hammering) ) Is included.

The standard sample measurement processing unit 422 executes standard sample measurement processing for causing the LCMS 3 to measure the standard sample. Specifically, a standard sample having a known concentration is sent to the LCMS 3 for measurement, whereby a calibration curve representing the relationship between the concentration and the detected intensity is created. The analysis processing unit 423 executes an analysis process for analyzing the culture medium sample in the LCMS 3. The calibration curve created by the standard sample measurement processing unit 422 is used for analysis processing in the analysis processing unit 423.

FIG. 2 is a flowchart showing a flow when performing analysis using the analysis system of FIG. In performing the analysis, first, the stabilization process is performed in the LCMS 3 by the stabilization process unit 421 and the standard sample measurement process unit 422 of the LCMS control unit 42 (step S101: stabilization process step), and the standard sample. A measurement process is executed (step S102: standard sample measurement process step).

After the stabilization process and the standard sample measurement process are performed, the medium sample is automatically loaded from the culture apparatus 1 to the pretreatment apparatus 2 by the pretreatment execution unit 411 of the pretreatment control unit 41. Preprocessing is performed (steps S103 and S104: preprocessing execution step). In addition, before a culture medium sample is carried in from the culture apparatus 1 to the pretreatment apparatus 2, the medium is sent to the flow path from the culture apparatus 1 to the pretreatment apparatus 2 to perform the co-washing.

When the pretreatment for the culture medium sample is completed, the pretreatment medium sample is automatically fed from the pretreatment device 2 to the LCMS 3 by the liquid feeding processing unit 412 (liquid feeding processing step), and the LCMS 3 is analyzed by the analysis processing unit 423. The analysis process is executed (step S105: analysis process step). At this time, the pretreated medium sample is automatically diluted and then analyzed by LCMS3.

After the analysis in the LCMS 3 is started, the culture apparatus 1 and the pretreatment apparatus 2 perform cleaning by the cleaning processing unit 413 (cleaning processing step). That is, the line cleaning is performed by supplying the cleaning liquid to the flow path from the culture apparatus 1 to the pretreatment apparatus 2 (step S106), and the flow path of the culture medium sample in the pretreatment apparatus 2 is washed with the cleaning liquid. (Step S107).

The processing of steps S103 to S107 is automatically and repeatedly performed on a plurality of medium samples sequentially transported from the culture apparatus 1. When the processing for all the medium samples is completed (Yes in step S108), the stabilization processing unit 421 and the standard sample measurement processing unit 422 of the LCMS control unit 42 perform the stabilization processing in the LCMS 3 after analysis. (Step S109), a standard sample measurement process is executed (Step S110). However, the stabilization process (step S109) at the end of the analysis may be omitted.

Thereafter, a calibration curve is created using the results of the standard sample measurement processing performed in steps S102 and S110, respectively. Specifically, a calibration curve is created using the average value of the results of each standard sample measurement process. After the above processing is performed, the LCMS 3 cools down by stopping the supply of the mobile phase and gas (step S111).

As shown in FIG. 2, in this embodiment, the stabilization process and standard sample measurement process in the LCMS 3, the loading of the medium sample from the culture apparatus 1 to the pretreatment apparatus 2, and the pretreatment apparatus 2 to the LCMS 3 The processed medium sample is automatically fed (steps S101 to S105). Further, after pre-processing and analysis for a plurality of medium samples are automatically performed repeatedly (Yes in step S108), stabilization processing and standard sample measurement processing in the LCMS 3 are automatically performed again (steps S109 and 110). .

This enables the standard sample measurement process to be automatically performed before and after the pretreatment and analysis for a plurality of medium samples, thereby creating a calibration curve. If the analysis in the LCMS 3 is performed using the calibration curve created in this way, it is possible to prevent the accuracy of the analysis result from being lowered due to a change with time. Therefore, it is not necessary for the operator to perform complicated work, and the analysis can be performed efficiently and accurately.

FIG. 3 is a flowchart showing a first modification of the process during analysis. The processing in steps S201 to S208 in FIG. 3 is the same as the processing in steps S101 to S108 in FIG.

In this example, the processes in steps S203 to S207 are automatically and repeatedly performed for a plurality of medium samples sequentially carried out from the culture apparatus 1, and when the processes for all the medium samples are completed (Yes in step S208). ) The number of the plurality of medium samples carried out from the culture apparatus 1 is compared with a predetermined threshold value (number of samples) (step S209). The threshold value may be a fixed value or may be set to an arbitrary value by the operator.

When the number of samples is equal to or greater than the threshold (Yes in step S209), the stabilization processing unit 421 and the standard sample measurement processing unit 422 of the LCMS control unit 42 perform the stabilization processing in the LCMS 3 after analysis ( Step S210), a standard sample measurement process is executed (step S211). Then, after a calibration curve is created using the results of the standard sample measurement processing performed in steps S202 and S211, the LCMS 3 is cooled down (step S212).

On the other hand, when the number of samples is less than the threshold (No in step S209), the stabilization process (step S210) and the standard sample measurement process (step S211) in the LCMS 3 after the analysis are omitted. In this case, a calibration curve is created using only the result of the standard sample measurement process performed in step S202, and the LCMS 3 is cooled down (step S212).

As described above, in this embodiment, when the number of medium samples is relatively small (No in step S209), the stabilization process and the standard sample measurement process in the LCMS 3 after the analysis are omitted, so the analysis time is shortened. In addition, it is possible to reduce the consumption of consumables (such as a mobile phase) accompanying the analysis. When the number of medium samples is relatively small, the accuracy of the analysis results is less likely to deteriorate due to changes over time. Therefore, even if the stabilization process and the standard sample measurement process in the LCMS 3 after the analysis are omitted, the analysis can be performed with high accuracy. .

FIG. 4 is a flowchart showing a second modification of the process during analysis. The processing in steps S301 to S308 in FIG. 4 is the same as the processing in steps S101 to S108 in FIG.

In this example, the processes in steps S303 to S307 are automatically and repeatedly performed on a plurality of medium samples sequentially carried out from the culture apparatus 1, and when the processes on all the medium samples are completed (Yes in step S308). ) The storage periods of the plurality of medium samples carried out from the culture apparatus 1 are compared with a predetermined threshold value (period) (step S309). The storage period is an upper limit of a period during which a medium sample can be stored, and the storage period is short in the case of a biological medium sample. The threshold value may be a fixed value or may be set to an arbitrary value by the operator.

When the storage period of the medium sample is equal to or longer than the threshold (Yes in step S309), the stabilization process is performed on the LCMS 3 after the analysis by the stabilization processing unit 421 and the standard sample measurement processing unit 422 of the LCMS control unit 42. In step S310, standard sample measurement processing is executed (step S311). Then, after a calibration curve is created using the results of the standard sample measurement processing performed in steps S302 and S311, the LCMS 3 is cooled down (step S312).

On the other hand, when the storage period of the culture medium sample is less than the threshold (No in Step S309), the stabilization process (Step S310) and the standard sample measurement process (Step S311) in the LCMS 3 after the analysis are omitted. In this case, a calibration curve is created using only the result of the standard sample measurement process performed in step S302, and the LCMS 3 is cooled down (step S312).

As described above, in this embodiment, when the storage period of the medium sample is relatively short (No in step S309), the stabilization process and the standard sample measurement process in the LCMS 3 after the analysis are omitted, and thus the analysis time is shortened. In addition, it is possible to reduce the consumption of consumables (such as mobile phase) accompanying the analysis. If the storage period of the culture medium sample is relatively short, it is necessary to evaluate the culture medium sample in a short time after feeding. Therefore, the analysis is performed accurately by omitting the stabilization process and the standard sample measurement process in LCMS3 after the analysis. be able to.

In the above embodiment, the case where the control unit 4 functions as the stabilization processing unit 421 has been described. However, the configuration may be such that the stabilization processing unit 421 (stabilization processing step) is omitted. Moreover, the analysis system to which the present invention is applied only needs to have a configuration including a mass spectrometer (MS unit), and may not have a liquid chromatograph (LC unit). That is, instead of the LCMS 3 in which a mass spectrometer and a liquid chromatograph are combined, a configuration in which only a mass spectrometer is provided may be used.

In the above embodiment, the configuration of the analysis system has been described. However, it is also possible to provide a program (analysis control program) for causing a computer to function as a control unit of the analysis system. In this case, the program may be provided in a state stored in a storage medium, or may be configured such that the program itself is provided.

1 Incubator 2 Pretreatment device 3 LCMS
4 Control Unit 41 Pretreatment Control Unit 42 LCMS Control Unit 411 Pretreatment Execution Unit 412 Liquid Supply Processing Unit 413 Washing Processing Unit 421 Stabilization Processing Unit 422 Standard Sample Measurement Processing Unit 423 Analysis Processing Unit

Claims

An analysis system for analyzing a plurality of medium samples carried out from a culture apparatus,
A pretreatment device for sequentially performing pretreatment on a plurality of medium samples;
A mass spectrometer for sequentially analyzing each culture medium sample pretreated by the pretreatment device;
A controller for controlling the pretreatment device and the mass spectrometer,
The controller is
A standard sample measurement processing unit for performing a standard sample measurement process for measuring a standard sample in the mass spectrometer;
After the processing by the standard sample measurement processing unit, a pretreatment execution unit that automatically carries a medium sample from the culture device to the pretreatment device and causes the pretreatment device to perform pretreatment,
A liquid sample is automatically fed to the mass spectrometer after the pretreatment, and includes a liquid feeding processing unit that causes the mass spectrometer to perform analysis.
After the processing by the pretreatment execution unit and the liquid feeding processing unit is repeatedly and automatically performed on a plurality of medium samples, the standard sample measurement processing is executed in the mass spectrometer after analysis. Analysis system.
2. The standard sample measurement process in the mass spectrometer after analysis is omitted when the number of medium samples carried out from the culture apparatus is less than a predetermined number of samples. Analysis system described in.
2. The standard sample measurement process in the mass spectrometer after analysis is omitted when the storage period of the plurality of medium samples carried out from the culture apparatus is less than a predetermined period. Analysis system described in.
The control unit further includes a stabilization processing unit that performs a stabilization process for stabilizing the mass spectrometer,
The pretreatment execution unit automatically loads a culture medium sample from the culture device to the pretreatment device after the processing by the stabilization processing unit and the standard sample measurement processing unit, and performs the pretreatment on the pretreatment device. The analysis system according to claim 1, wherein:
A liquid chromatograph having a column into which the medium sample is introduced, and separating each component in the medium sample in the process of passing through the column;
The analysis system according to any one of claims 1 to 4, wherein the mass spectrometer performs mass spectrometry on each component separated in the liquid chromatograph.
An analysis method for sequentially performing pretreatment on a plurality of medium samples carried out from a culture apparatus with a pretreatment apparatus and sequentially analyzing each medium sample on which pretreatment has been performed,
A standard sample measurement process step for executing a standard sample measurement process for measuring a standard sample in the mass spectrometer;
After the processing by the standard sample measurement processing step, a pretreatment execution step for automatically loading a culture medium sample from the culture device to the pretreatment device and causing the pretreatment device to perform pretreatment;
A liquid sample is automatically fed to the mass spectrometer after the pretreatment, and the mass spectrometer performs analysis.
The process according to the pretreatment execution step and the liquid feeding treatment step is repeatedly and automatically performed on a plurality of medium samples, and then the standard sample measurement process is executed in the mass spectrometer after the analysis. Analysis method.
The said standard sample measurement process in the said mass spectrometer after an analysis is abbreviate | omitted when the number of the some culture medium samples carried out from the said culture | cultivation apparatus is less than the predetermined number of samples. The analysis method described in 1.
The said standard sample measurement process in the said mass spectrometer after an analysis is abbreviate | omitted when the preservation | save period of the several culture medium sample carried out from the said culture | cultivation apparatus is less than predetermined period. The analysis method described in 1.
A stabilization process step of performing a stabilization process for stabilizing the mass spectrometer;
In the preprocessing execution step, after the processing in the stabilization processing step and the standard sample measurement processing step, the culture medium sample is automatically carried from the culture device to the pretreatment device, and the pretreatment device performs preprocessing. The analysis method according to claim 6, wherein:
An analysis control program for sequentially performing pretreatment with a pretreatment device on a plurality of medium samples carried out from a culture apparatus, and sequentially analyzing each medium sample subjected to pretreatment with a mass spectrometer,
A standard sample measurement process step for executing a standard sample measurement process for measuring a standard sample in the mass spectrometer;
After the processing by the standard sample measurement processing step, a pretreatment execution step for automatically loading a culture medium sample from the culture device to the pretreatment device and causing the pretreatment device to perform pretreatment;
The medium sample after the pretreatment is automatically sent to the mass spectrometer, and the computer is caused to perform a liquid feeding process step for causing the mass spectrometer to perform analysis,
After the processing by the pretreatment execution step and the liquid feeding processing step is repeatedly and automatically performed on a plurality of medium samples, the standard sample measurement processing is executed in the mass spectrometer after analysis. Analysis control program.
11. The standard sample measurement process in the mass spectrometer after analysis is omitted when the number of medium samples carried out from the culture apparatus is less than a predetermined number of samples. Analysis control program described in 1.
11. The standard sample measurement process in the mass spectrometer after analysis is omitted when the storage period of the plurality of medium samples carried out from the culture apparatus is less than a predetermined period. Analysis control program described in 1.
Causing the computer to further execute a stabilization process step of performing a stabilization process for stabilizing the mass spectrometer,
In the preprocessing execution step, after the processing in the stabilization processing step and the standard sample measurement processing step, the culture medium sample is automatically carried from the culture device to the pretreatment device, and the pretreatment device performs preprocessing. The analysis control program according to claim 10, wherein: