JP-7856106-B2 - Information delivery methods, analysis systems, and programs

Inventors

• 蓮沼 誠久

Assignees

• 株式会社島津製作所

Dates

Publication Date

20260511

Application Date

20220304

Priority Date

20210831

Claims (9)

1. A method for providing information on metabolites, The steps include supplying the culture medium in the container to the first tube, The steps include obtaining the weight of metabolites identified by a liquid chromatograph-mass spectrometer in the culture medium supplied to the first tube, The steps include supplying the culture medium in the container to a second tube different from the first tube, The method comprises the step of obtaining the weight of microorganisms identified by the liquid chromatograph-mass spectrometer in the culture medium supplied to the second tube, The weight of the metabolite is determined for the culture medium after it has been quenched to stop the metabolic reaction of the microorganism. The weight of the microorganism is determined for the culture medium that has not undergone the quenching treatment. The method of providing the aforementioned information further includes, The steps include: deriving an index relating to the weight of the metabolite using the reciprocal of the weight of the metabolite and the weight of the microorganism; The step of outputting the aforementioned indicator, The step of deriving the aforementioned index includes deriving the index by calculating the product of the weight of the metabolite and the reciprocal of the weight of the microorganism.
2. The information provision method according to claim 1 , wherein the second tube is supplied with the same amount of culture medium as the amount supplied to the first tube.
3. The information-providing method according to claim 1 or 2 , wherein the quenching treatment includes mixing a drug that stops the metabolic reaction of microorganisms in the culture medium with the culture medium.
4. An analytical system that provides information on the weight of microbial metabolites, Information processing equipment and A sampling device, Equipped with a liquid chromatograph-mass spectrometer, The sampling device is The culture solution of microorganisms in the container is supplied to a first tube and a second tube different from the first tube. The aforementioned information processing device is The culture medium supplied to the first tube, after being subjected to a quenching treatment to stop the metabolic reaction of the microorganisms, is used to obtain the weights of metabolites identified by the liquid chromatograph-mass spectrometer. The culture medium supplied to the second tube, which has not undergone the quenching treatment, is used to obtain the weight of microorganisms identified by the liquid chromatograph-mass spectrometer. Using the weight of the metabolite and the reciprocal of the weight of the microorganism, an index relating to the weight of the metabolite is derived. It is configured to output the aforementioned indicator, The aforementioned index is derived by calculating the product of the weight of the metabolite and the reciprocal of the weight of the microorganism , in an analytical system.
5. The analytical system according to claim 4 , wherein the second tube is supplied with the same amount of culture medium as the amount supplied to the first tube.
6. The analytical system according to claim 4 or 5 , wherein the quenching treatment includes mixing a drug that stops the metabolic reactions of microorganisms in the culture medium with the culture medium.
7. A computer program that provides information about metabolites, To the aforementioned computer, The steps include supplying the culture medium in the container to the first tube, The steps include obtaining the weight of metabolites identified by a liquid chromatograph-mass spectrometer in the culture medium supplied to the first tube, The steps include supplying the culture medium in the container to a second tube different from the first tube, The process involves performing the step of obtaining the weight of microorganisms identified by the liquid chromatograph-mass spectrometer in the culture medium supplied to the second tube, The weight of the metabolite is determined for the culture medium after it has been quenched to stop the metabolic reaction of the microorganism. The weight of the microorganism is determined for the culture medium that has not undergone the quenching treatment. The aforementioned computer further, The steps include: deriving an index relating to the weight of the metabolite using the reciprocal of the weight of the metabolite and the weight of the microorganism; The step of outputting the aforementioned indicator is performed, A program that derives the index by calculating the product of the weight of the metabolite and the reciprocal of the weight of the microorganism .
8. The program according to claim 7 , wherein the second tube is supplied with the same amount of culture medium as the amount supplied to the first tube.
9. The program according to claim 7 or 8 , wherein the quenching process includes mixing a drug into the culture medium to stop the metabolic reactions of microorganisms in the culture medium.

Description

This disclosure relates to methods, analytical systems, and programs for providing information on metabolites. As disclosed in Patent Document 1, there is a known apparatus for culturing cells such as microorganisms by adjusting the dissolved oxygen concentration while stirring the culture medium in a container. International Publication No. 2020/017407 This is a diagram showing the schematic configuration of the automated preprocessing system.This is a flow path diagram showing the flow path configuration of the sampling device.This is a block diagram illustrating the schematic configuration of the control device.This figure shows the skim for obtaining the weight of metabolites and the weight of microorganisms in the culture medium of the cell culture device 100.This is a flowchart for the process of outputting an index of metabolite weights.This figure shows the volume of liquid supplied to the tube for weighing microorganisms and the volume of liquid supplied to the tube for weighing metabolites in the analysis system 700. This embodiment will be described in detail with reference to the drawings. Note that identical or corresponding parts in the drawings are denoted by the same reference numerals, and their descriptions will not be repeated in principle. <Outline of the analysis system configuration> Figure 1 is a block diagram showing the schematic configuration of the analysis system 700. The analysis system 700 includes a liquid chromatograph-mass spectrometer 3, an automated sample preparation system 10, and an information processing device 70. The automated sample preparation system 10 is a device for automatically performing sample preparation on the analyte for the liquid chromatograph-mass spectrometer 3. An example of an analyte is cultured microorganisms. Another example is microbial metabolites. The information processing device 70 can communicate with the automated sample preparation system 10 and the liquid chromatograph-mass spectrometer 3 and controls the analysis system 700 as a whole. The information processing device 70 includes a CPU (Central Processing Unit) 51, memory 72, communication interface 73, input device 74, and display 75. The memory 72 is composed of, for example, ROM (Read Only Memory) and RAM (Random Access Memory), and can store control programs and various other data non-temporarily. The communication interface 73 is implemented, for example, by a network card, and enables the information processing device 70 to communicate with the automated preprocessing system 10 and the liquid chromatograph-mass spectrometer 3. The input device 74 inputs data from the user to the CPU 71 and is implemented, for example, by a keyboard and/or mouse. The display 75 displays the calculation results of the CPU 71 and is implemented, for example, by a liquid crystal display. The automated sample preparation system 10 includes a sampling device 1 and a sample preparation device 2. In the automated sample preparation system 10, metabolites of microorganisms are extracted from the microorganisms after sample preparation. The extracted metabolites are supplied to a liquid chromatograph-mass spectrometer 3. The liquid chromatograph-mass spectrometer 3 is merely one example of an analytical device for analyzing an analyte. It is also possible to analyze an analyte using other analytical devices. The sampling device 1 is a device for sampling liquid from a container (culture vessel). For example, microorganisms are cultured in a culture medium containing a culture culture medium inside a container called a bioreactor. The bioreactor is equipped with, for example, a stirring member that rotates using magnetic force, and an oxygen concentration sensor for detecting the concentration of dissolved oxygen. By adjusting the dissolved oxygen concentration while stirring the culture medium and the culture medium containing microorganisms inside the bioreactor, microorganisms are cultured inside the sampling device 1. The pretreatment device 2 pre-treats the microorganisms contained in the culture medium (culture sample) sampled from the bioreactor. In the sampling device 1, the culture medium is contained in a tube. The pretreatment device 2 includes a centrifugation mechanism 4, a liquid removal mechanism 5, a reagent supply mechanism 6, a stirring mechanism 7, and an extraction mechanism 8. Each of these mechanisms sequentially performs pre-treatment on the culture medium in the tube. The centrifugal separation mechanism 4 applies centrifugal force to the culture medium in the tube. This separates the culture medium into a solid component that settles at the bottom of the tube and a liquid component that floats above the solid component, with the solid-liquid interface as the boundary. The solid component is the culture (for example, cultured microorganisms). The liquid component floating above the solid component is the supernatant separated from the culture medium. The liquid removal mechanism 5 as