Biological metabolism process control system

Abstract

The utility model provides a biological metabolism process control system, and belongs to the technical field of biological metabolism control systems.The biological metabolism process control system comprises a culture unit, the culture unit is a bioreactor, the culture unit is connected with a detection unit and an information processing unit, and the bioreactor is composed of a tank body, a tank cover, a base, a stirring device, a heating device and a ventilation device; the detection unit is composed of a first detection module and a second detection module, and the first detection module is composed of a mechanical motion structure, a sample collection structure, a sample treatment structure, an OD detection structure, an ion detection module and an enzyme membrane reaction tank structure; the second detection module is composed of a pipetting structure, a heating oscillation structure, a mechanical motion structure and an optical structure. The problems that an existing control system is large in workload, cannot effectively feed back and adjust metabolism of strains and is single in function are solved.

Description

Technical Field

[0001] The utility model relates to the field of biological metabolism control systems, and more specifically, to a biological metabolism process control system. Background Art

[0002] Existing bioreactors are mainly used for single microorganism or cell culture. During the culture process, the control of process parameters is mainly carried out through off-line manual sampling and detection. Conventional detection usually uses common analytical instruments or methods for detection and analysis, such as spectrophotometers, titration methods, liquid phase or gas phase, etc. to detect the changes of important parameters and target products in process control. There are several problems with the detection of important parameters in the culture process using this method. The detection process generally takes a long time from sampling to obtaining results. For experiments involving multiple fermenters, it will greatly increase the detection time of the detector, with low efficiency and being unfavorable for the process regulation of experimenters. It is easy to cause untimely process regulation in the culture process, long data acquisition time, few detected parameters, and inability to provide timely feedback on substrates and products during the entire microorganism or cell fermentation culture process. For fermentation personnel, exploring the relationship between substrate consumption and product formation is an extremely important regulation means, which is convenient for well regulating the entire target microorganism or cell, thus forming a stable process for scale-up industrialization and providing greater social benefits.

[0003] Patent CN201710643960.3 discloses a microbial metabolite detection system and a detection quality control method. The main feature of the detection system is that it includes a reaction unit, a measurement unit, and a storage unit; the reaction unit is coated with a microbial metabolite probe for detecting the microbial metabolites in the target test substance placed in the reaction unit, and the measurement unit is used to measure the microbial metabolite data information in the reaction unit and store it in the storage unit. Its structural form is as Figure 1 shown. The above control method requires preparing fluorescence probes for each product, increasing the workload, and cannot effectively feedback and regulate the metabolism of the strain, with relatively single functions; the parameters obtained during the microorganism or cell culture process are not comprehensive, the product detection is not timely, it is difficult to explore the relationship between substrate consumption and product formation, and the process regulation is unstable.

[0004] Therefore, we make improvements on this and propose a biological metabolism process control system. Summary of the Utility Model

[0005] The purpose of the utility model is to address the problems existing in the current control system, such as large workload, inability to effectively feedback and regulate the metabolism of the strain, and relatively single functions.

[0006] To achieve the above-mentioned invention purpose, the utility model provides the following technical solutions:

[0007] A biological metabolism process control system to improve the above problems.

[0008] Specifically, this application is as follows:

[0009] It includes a culture unit, which is a bioreactor. The culture unit is connected to a detection unit and an information processing unit. The bioreactor consists of a tank body, a tank cover, a base, a stirring device, a heating device, and a ventilation device. The detection unit consists of a first detection module and a second detection module. The first detection module consists of a mechanical movement structure, a sample collection structure, a sample processing structure, an OD detection structure, an ion detection module, and an enzyme membrane reaction pool structure. The second detection module consists of a pipetting structure, a heating and shaking structure, a mechanical movement structure, and an optical structure. The information processing unit is controlled by an information program and consists of a host and a display screen.

[0010] As a preferred technical solution of this application, in the culture unit, the tank body and the tank cover form a containing space. Inside the space, there is a stirring shaft with blades on it, which is driven by the stirring device. The stirring device is driven by a motor, and there is a heating device outside the tank body. The ventilation device is provided with a gas source by an air compressor. Through the ventilation channel on the tank cover, the air entering the tank body has a gas filtering device in front of it.

[0011] As a preferred technical solution of this application, in the first detection module, the ion detection module consists of a reaction pool. After the sample is diluted by the sample dilution structure, it is transported to the reaction pool. The reaction pool is a cuboid structure, and the relevant ion electrodes to be measured are located above.

[0012] As a preferred technical solution of this application, the OD detection structure includes a transparent industrial syringe, a light source device, and an optical fiber.

[0013] As a preferred technical solution of this application, the mechanical movement structure is divided into a sample retention structure and a dilution structure, and the whole structure consists of an X-axis, a Y-axis, and a Z-axis.

[0014] As a preferred technical solution of this application, the sample collection structure consists of a sample retention orifice plate with a specification of 10 mL. The enzyme membrane reaction pool structure consists of two four-channel enzyme membrane reaction pools. Each channel is connected to an electrode, and an enzyme membrane is installed at the end of the electrode. A filtration pool is arranged on the left side of the sample retention orifice plate.

[0015] As a preferred technical solution of this application, the sample processing structure includes dilution processing and raw solution filtration processing. The dilution processing is a cylindrical pool with corresponding channel openings on it. The second detection module destroys the cell structure through heating, shaking, and sedimentation processing to detect the products inside and outside the cells.

[0016] Compared with the prior art, the beneficial effects of the present utility model are as follows:

[0017] In the solution of this application:

[0018] 1. For the first time, this system integrates the microbial / cell culture process and the substrate / product detection process, and for the first time proposes a new concept;

[0019] 2. It realizes a control platform integrating microbial / cell culture, realizes the automatic control of the microbial / cell culture process and results, reduces manual operation, and lowers labor costs; it has multiple detection parameters and high flexibility; it realizes the detection of intracellular and extracellular products. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a schematic diagram of a biological metabolism process control system of the present utility model;

[0021] Figure 2 It is a schematic diagram of the connection structure of the fermenter and the sample retention pipeline of the present utility model;

[0022] Figure 3 It is a flow chart of the process detection method of the present utility model.

[0023] In the figure: 1. Culture unit; 2. Detection unit; 3. Information processing unit; 4. Fermenter; 5. Sample retention pipeline; 6. Sample retention orifice plate; 7. Filter pool; 8. First dilution pool; 9. Second dilution pool; 10. Sample delivery pipeline; 11. Ion electrode; 12. Enzyme membrane electrode; 13. OD injection pump; 14. Intracellular and extracellular product module. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0024] To make the objectives, technical solutions, and advantages of the embodiments of the present utility model clearer, the technical solutions in the embodiments of the present utility model will be clearly and completely described below with reference to the accompanying drawings. Apparently, the described embodiments are some but not all of the embodiments of the present utility model.

[0025] Therefore, the following detailed description of the embodiments of the present utility model is not intended to limit the scope of the present utility model claimed, but merely represents some embodiments of the present utility model. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present utility model without creative efforts fall within the scope of protection of the present utility model.

[0026] It should be noted that, without conflict, the embodiments in the present utility model and the features and technical solutions in the embodiments may be combined with each other.

[0027] It should be noted that like reference numerals and letters refer to like items in the following figures. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0028] In the description of the present utility model, it should be noted that the orientation or positional relationship indicated by terms such as "upper", "lower", etc. is based on the orientation or positional relationship shown in the figures, or the orientation or positional relationship in which the invention product is usually placed during use, or the orientation or positional relationship commonly understood by those skilled in the art. Such terms are only for the convenience of describing the present utility model and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation to the present utility model. In addition, terms such as "first", "second", etc. are only used for distinguishing descriptions and cannot be understood as indicating or implying relative importance.

[0029] Embodiment 1:

[0030] As Figures 1 - 3 shown, this embodiment proposes a biological metabolism process control system, including a culture unit 1, which is connected to a detection unit 2 and an information processing unit 3. The culture unit 1 is a bioreactor, and the culture object is microorganisms or cells, which is filled with a culture medium for culturing microorganisms or cells;

[0031] The bioreactor is composed of main systems such as a stirring system, a dissolved oxygen system, an acid-base system, a temperature system, etc., and its material is not limited.

[0032] When microorganisms or cells are cultured in the culture unit 1, according to relevant metabolism, primary metabolites and secondary metabolites can be produced, including the target metabolite.

[0033] According to the metabolites produced in the culture unit 1, the growth state of microorganisms or cells can be controlled and adjusted to make them grow in the desired positive direction and improve their titer.

[0034] The culture solution in the culture unit 1, that is, the sample of microorganisms or cells, needs to be detected for its physical and chemical parameters after a certain period of culture, detecting substrate consumption and product generation, and judging cell metabolism level, cell growth quality, etc.

[0035] The sample in the culture unit 1 is transported to the detection unit 2, and the sample is first diluted with deionized water, and the sample after the first dilution is further diluted with deionized water for the second time.

[0036] The sample in detection unit 2 is diluted for the first time and then acted on by a peristaltic pump to be transported to the ion detection module for ion detection. The detection of ions is mainly carried out through corresponding electrodes. When detecting ionic electrons, a pH electrode is required as a reference electrode. The ions detected are mainly used to judge the consumption of ions during the fermentation process and to judge the growth of bacterial strains.

[0037] In detection unit 2, the detection of glucose, lactose, glutamic acid, acetic acid, glutamic acid, etc. can realize the detection of microbial products and substrates. The sample to be tested is diluted. Deionized water is preferably selected as the diluent, and the appropriate dilution factor can be selected according to the concentration of the sample to be tested. Specifically, the described sample dilution is the first dilution of the sample to be tested. After the first dilution, the sample after the first dilution is used as the sample for the second dilution. The diluted sample enters the second dilution tank 9. It should be noted that the detection method of the sample detection tank here is to use the enzyme membrane electrode 12 for detection. Here, it is specifically stated that each detection item corresponds to a relevant enzyme membrane. Before detection, the enzyme membrane matching the detection item needs to be replaced. The number of detections is a four-channel enzyme membrane, and the appropriate channel detection item can be selected, and at most the substances in the fermenter 4 can be detected.

[0038] The sample detection of the information processing unit 3 can detect the intracellular and extracellular substances in the sample. The sample taken is the sample in detection unit 2. Similarly, the sample is diluted. The diluent is deionized water, and the matching detection concentration is selected. The sample treatment process is the same as the above sample treatment process. During this process, the treated sample is transported through a dedicated sample delivery pipeline 10, and the sample delivery pipeline 10 transports the treated sample to the information processing unit 3 for intermediate detection.

[0039] Example 2:

[0040] The solution in Example 1 will be further introduced below in combination with the specific working mode. See the following description for details:

[0041] As Figure 2 shown, as a preferred implementation method, on the basis of the above method, further, the sample in detection unit 2 is diluted for the first time and then acted on by an industrial injection pump, and the OD is detected through the industrial injection pump. The OD injection pump 13 is used to detect the OD to judge the growth state of the bacterial cells.

[0042] As Figure 1 and Figure 2As shown, as a preferred embodiment, on the basis of the above method, further, in the detection unit 2, ions are detected by the ion electrode 11. The detected ions are mainly potassium, sodium, calcium, magnesium and other ions. The steps of the above detection process are as follows: the detected sample is first diluted in the first dilution cell 8 with deionized water as the diluent, and the diluted sample is sent to the ion detection cell. It should be clear that the pH electrode is required as a reference electrode for detecting the target ions.

[0043] As Figures 1 - 3 shown, as a preferred embodiment, on the basis of the above method, further, the system is a bioreactor for culturing microorganisms or cells. The fermentation broth is transported to the on-line detection system through pipelines. After the sample is diluted, OD, ions, enzyme membranes and intra- and extracellular products are detected. The whole system realizes the integration of microorganism or cell culture, detection and analysis of the culture process and results, that is, realizes the reverse real-time regulation of the process from process parameters and result analysis. Using this system, excellent strains can be screened and the fermentation process can be optimized.

[0044] As Figure 2 shown, as a preferred embodiment, on the basis of the above method, further, the system mainly includes the following three module systems: Module 1 is a bioreactor, Module 2 is an automatic on-line detection, and Module 3 is an intra- and extracellular product module 14.

[0045] As Figure 2 shown, as a preferred embodiment, on the basis of the above method, further, the structure of Module 2 is changed. The main change is to remove the stock solution tank. The sample passes through the sampling pipeline 5 to the sample storage box. The sample storage box has two functions: sampling function and stock solution storage function.

[0046] Specifically, when this biological metabolism process control system is in use:

[0047] The working principle of the system is that the culture object is cultured in the culture unit 1. The sample is transported to the detection unit 2 through the transport pipeline. After the sample is pretreated, an enzyme membrane is used to detect the substrate and product. The OD is detected by visible light, and the ions are detected by relevant electrodes. Correspondingly, after the sample is pretreated, it is transported to the information processing unit 3. The information processing unit 3 reprocesses the sample running in the detection unit 2. This step includes sedimentation, heating, cooling, shaking and other treatments of the sample in the detection unit 2. After the above methods are used, the relevant sample can be detected again.

[0048] The above embodiments are only used to illustrate the present utility model and not to limit the technical solutions described by the present utility model. Although the present specification has described the present utility model in detail with reference to the above respective embodiments, the present utility model is not limited to the above specific implementation manners. Therefore, any modification or equivalent replacement of the present utility model; and all technical solutions and their improvements that do not depart from the spirit and scope of the invention are covered by the scope of the claims of the present utility model.

Claims

1. A biological metabolic process control system, comprising a culture unit (1), characterized in that: The culture unit (1) is a bioreactor, and the culture unit (1) is connected to a detection unit (2) and an information processing unit (3). The bioreactor is composed of a tank body, a tank cover, a base, a stirring device, a heating device and a ventilation device. The detection unit (2) is composed of a first detection module and a second detection module. The first detection module is composed of a mechanical motion structure, a sample collection structure, a sample processing structure, an OD detection structure, an ion detection module and an enzyme membrane reaction pool structure. The second detection module is composed of a liquid transfer structure, a heating and oscillation structure, a mechanical motion structure and an optical structure. The information processing unit (3) is controlled by an information program and is composed of a host and a display screen.

2. A biological metabolic process control system according to claim 1, characterized in that: The tank body and the tank cover in the culture unit (1) form a containing space, the interior of the space is provided with a stirring shaft, the stirring shaft has paddles on it, and is driven by the stirring device, the stirring device is driven by a motor, and the tank body is provided with a heating device on the outside; the ventilation device is provided with an air source by an air compressor, and a ventilation channel is provided on the tank cover, and a gas filter is provided in front of the air entering the channel of the tank body.

3. A biological metabolic process control system according to claim 1, characterized in that: In the first detection module, the ion detection module consists of a reaction pool. After the sample is diluted, it is transported to the reaction pool. The reaction pool is a rectangular structure, and the upper position is the relevant ion electrode (11) to be tested.

4. A biological metabolic process control system according to claim 1, characterized in that: The OD detection structure includes a transparent industrial syringe, a light source device and an optical fiber.

5. A biological metabolic process control system according to claim 1, characterized in that: The mechanical motion structure is divided into a sample retention structure and a dilution structure, and the entire structure consists of an X-axis, a Y-axis and a Z-axis.

6. A biological metabolic process control system according to claim 1, characterized in that: The sample collection structure is composed of a sample retention hole plate (6) with a specification of 10 mL. The enzyme membrane reaction pool structure is composed of two four-channel enzyme membrane reaction pools, each channel is connected to an electrode, and the electrode end is equipped with an enzyme membrane. A filtering pool (7) is arranged on the left side of the sample retention hole plate (6).

7. A biological metabolic process control system according to claim 1, characterized in that: The sample processing structure includes dilution processing and stock solution filtration processing. The dilution processing is a cylindrical pool with corresponding channel openings on the pool. The second detection module destroys the cell structure through heating, shaking and sedimentation processing to detect intracellular and extracellular products.

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