Culture device and method of controlling culture device

Abstract

This culture device is for culturing microbes or cells which are used to proliferate a raw material gas containing a flammable gas or to produce an organic substance, the culture device comprising: a culture tank in which a culture liquid is accommodated; a raw material gas supply unit for supplying a raw material gas to the culture tank; and a compositional ratio control mechanism for measuring the compositional ratio of a mixed gas inside a space located above the liquid level of the culture liquid inside the culture tank and supplying an adjusting gas into the space in accordance with the measured compositional ratio of the mixed gas, thereby maintaining the compositional ratio of the mixed gas in the space at a preset target value outside an explosive range. The dimensions of the culture tank satisfy the condition H / DAm ≥ 2, where DAm is the equivalent circular diameter of a cross-section orthogonal to the height direction of the culture tank, and H is the maximum height of the liquid level.

Description

Cultivation device and control method for culture device

[0001] The technology of the present disclosure relates to a culture device and a control method for the culture device.

[0002] Research into the de-petroleumization of raw materials is active worldwide with the aim of reducing greenhouse gas emissions. As part of this research, technologies for utilizing carbon sources other than petroleum as raw materials have been developed in the fields of chemical and bioproduct manufacturing. For example, microorganisms are known that utilize carbon sources other than petroleum as raw materials for growth or for the production of organic substances. One example of such a microorganism is hydrogen-oxidizing bacteria. Hydrogen-oxidizing bacteria grow by consuming gases containing carbon dioxide, hydrogen, and oxygen as raw materials. Furthermore, genetic modification of hydrogen-oxidizing bacteria allows for the efficient production of organic substances such as alcohols and amino acids. Hydrogen-oxidizing bacteria is a collective term for chemosynthetic bacteria that utilize the energy generated by hydrogen oxidation to convert carbon from carbon dioxide into organic substances and incorporate them into the bacteria. Hydrogen-oxidizing bacteria are also attracting attention for their ability to effectively utilize carbon dioxide, a greenhouse gas, because carbon dioxide serves as a raw material for growth or the production of organic substances.

[0003] Japanese Patent Publication No. 2564008 and U.S. Patent Application Publication No. 2019 / 0316072 disclose a culture device for culturing hydrogen-oxidizing bacteria. The culture device includes a culture tank containing a culture solution. A feed gas containing carbon dioxide, hydrogen, and oxygen is supplied into the culture tank, and some of the carbon dioxide, hydrogen, and oxygen contained in the feed gas are dissolved in the culture solution and consumed for the growth of hydrogen-oxidizing bacteria or the production of organic substances. The remaining feed gas is released into a space above the surface of the culture solution in the culture tank and then exhausted to the outside of the culture tank. Mixed gases containing flammable hydrogen and oxygen may pose an explosion risk depending on the composition ratio, and therefore Japanese Patent Publication No. 2564008 and U.S. Patent Application Publication No. 2019 / 0316072 disclose a technology for suppressing explosions.

[0004] In Japanese Patent Publication No. 2564008, the supply of oxygen contained in the feed gas is independently controlled, the dissolved oxygen concentration in the culture solution is measured, and the amount of oxygen supplied to the culture tank is limited based on the measured dissolved oxygen concentration. In U.S. Patent Application Publication No. 2019 / 0316072, safety is ensured by controlling the components of the feed gas.

[0005] Furthermore, WO 2011 / 070791 and the like disclose culturing devices for culturing microorganisms and the like. WO 2011 / 070791 describes a technology for improving oxygen utilization efficiency by reducing the diameter of bubbles in a feed gas. JP 2013-005754 A and WO 2006 / 101074 A describe technologies for improving the solubility of a feed gas by using a vertically long culture tank as a culture tank. WO 2016 / 117023 describes a technology for suppressing damage to bacterial cells, which are microorganisms, in a culture tank, although the source gas is not a flammable gas.

[0006] In the case of a raw material gas containing a flammable gas, there is a risk of explosion of the mixed gas released from the culture solution in the culture tank, so a technique for suppressing the explosion is very important. All of the methods described in the above-mentioned Patent No. 2564008 and the like have room for improvement in safety measures for suppressing explosion.

[0007] The technology disclosed herein provides a culture device and a control method for the culture device that can improve safety compared to conventional methods when culturing microorganisms or cells that use raw material gases containing flammable gases for growth or production of organic substances.

[0008] In order to achieve the above object, a first culture apparatus according to the technology of the present disclosure is a culture apparatus for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances, and includes: a culture tank that contains a culture solution for culturing the microorganisms or cells; a raw material gas supply unit that supplies the raw material gas to the culture tank; a composition ratio control mechanism that measures the composition ratio of the mixed gas in a space present above the liquid surface of the culture solution in the culture tank and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosive range; a gas circulation path for reusing the mixed gas in the space as a raw material gas; and a dissolution rate control mechanism that measures a flammable gas solubility rate, which is the proportion of flammable gas dissolved in the culture solution out of the flammable gas contained in the raw material gas supplied to the culture tank through the gas circulation path or the raw material gas supply unit during culture, and maintains the measured flammable gas solubility rate at or above a predetermined target value.

[0009] A first control method for a culture apparatus according to the disclosed technology is a control method for a culture apparatus for culturing microorganisms or cells, the method comprising: a culture tank containing a culture solution for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances; and a raw material gas supply unit that supplies a raw material gas containing a flammable gas to the culture tank. The control method measures the composition ratio of a mixed gas in a space present above the liquid surface of the culture solution in the culture tank; and supplies an adjustment gas into the space according to the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosive range. During the culture, the control method measures a flammable gas solubility rate, which is the proportion of flammable gas dissolved in the culture solution among the flammable gases contained in the raw material gas supplied to the culture tank through a gas circulation path or the raw material gas supply unit for reusing the mixed gas in the space as a raw material gas, and maintains the measured flammable gas solubility rate at a predetermined target value.

[0010] A second culture apparatus according to the technology of the present disclosure is a culture apparatus for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances, and is equipped with a culture tank that contains a culture solution for culturing the microorganisms or cells, a raw material gas supply unit that supplies the raw material gas to the culture tank, and a composition ratio control mechanism that measures the composition ratio of the mixed gas in a space above the liquid surface of the culture solution in the culture tank and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosive range, where DAm is the equivalent circle diameter of a cross section perpendicular to the height direction of the culture tank and H is the maximum height of the liquid surface, and the dimensions of the culture tank satisfy the condition H / DAm≧2.

[0011] A second control method for a culture apparatus according to the technology of the present disclosure is a control method for a culture apparatus for culturing microorganisms or cells, the method comprising: a culture tank containing a culture solution for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances; and a raw material gas supply unit that supplies the raw material gas containing a flammable gas to the culture tank, wherein the dimensions of the culture tank satisfy the condition H / DAm≧2, where DAm is the equivalent circle diameter of a cross section perpendicular to the height direction of the culture tank, and H is the maximum height of the liquid surface; and the composition ratio of the mixed gas in the space present above the liquid surface of the culture solution in the culture tank is measured, and an adjustment gas is supplied into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosive range.

[0012] A third culture apparatus according to the technology of the present disclosure is a culture apparatus for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances, and is provided with a culture tank that contains a culture medium for culturing the microorganisms or cells, a culture medium tank that stores the culture medium to be supplied to the culture tank, a culture subject supply path that supplies the microorganisms or cells to the culture tank, a raw material gas tank that stores the raw material gas, a bubble generator for mixing the raw material gas with the culture medium before it is supplied to the culture tank, and a culture medium supply path that is disposed between the culture medium tank and the culture tank and supplies the culture medium mixed with the raw material gas by the bubble generator to the culture tank, the culture medium supply path being provided separately from the culture subject supply path.

[0013] A fourth culture apparatus according to the technology of the present disclosure is a culture apparatus for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances, and includes a culture tank that contains a culture solution for culturing the microorganisms or cells, a raw material gas supply unit that supplies the raw material gas to the culture tank, a gas circulation path for reusing a mixed gas in a space above the liquid surface of the culture solution in the culture tank as the raw material gas, and a pressure-applying device that is disposed on the gas circulation path and applies a circulation pressure to the mixed gas to circulate the mixed gas, and the pressure-applying device has no mechanically moving parts and applies a circulation pressure to the mixed gas by a driving fluid input from outside to the pressure-applying device.

[0014] According to the technology of the present disclosure, safety can be improved compared to conventional methods when culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances.

[0015] 1 is a diagram explaining the function of the culture apparatus. FIG. 1 is a diagram illustrating the overall configuration of the culture apparatus. FIG. 2 is a diagram illustrating a configuration for supplying raw material gas component by component. FIG. 3 is a diagram illustrating a configuration for recovering and reusing culture solution. FIG. 4 is a diagram illustrating a configuration for separating a specific component from culture solution. FIG. 5 is a diagram illustrating the arrangement of a culture solution outlet. FIG. 6 is a diagram illustrating an index of bubble diameter. FIG. 7 is a diagram illustrating a surface tension reducing agent. FIG. 8 is a diagram illustrating a configuration for reusing waste gas. FIG. 9 is a diagram illustrating a configuration used for various controls. FIG. 10 is a diagram illustrating a configuration for controlling the composition ratio of a mixed gas. FIG. 11 is a diagram illustrating a configuration for dissolution rate control and consumption rate control. FIG. 12 is a flowchart of a process for controlling the composition ratio of a mixed gas. FIG. 13 is a flowchart of a process for controlling the dissolution rate of hydrogen. FIG. 14 is a flowchart of a process for controlling the consumption rate of hydrogen. FIG. 15 is a diagram illustrating the effect of the first embodiment. FIG. 16 is a diagram illustrating a culture tank of the second embodiment. FIG. 17 is a diagram illustrating a first modified example of the culture tank of the second embodiment. FIG. 18 is a diagram illustrating a second modified example of the culture tank of the second embodiment. FIG. 19 is a diagram illustrating a third modified example of the culture tank of the second embodiment. FIG. 20 is a diagram illustrating a fourth modified example of the culture tank of the second embodiment. FIG. 21 is a diagram illustrating a culture apparatus of the third embodiment. FIG. 22 is a diagram illustrating a culture apparatus of the fourth embodiment. FIG. 23 is a diagram illustrating a modified example of the culture apparatus of the fourth embodiment.

[0016] "Table of Contents" 1. Example of common configuration of each embodiment 2. First embodiment 3. Second embodiment 4. Third embodiment 5. Fourth embodiment

[0017] 1. An example of a common configuration of each embodiment First, an example of a common configuration of the culture device according to each embodiment of the technology of the present disclosure is shown using Figures 1 to 9. Then, in Figure 10 and subsequent figures, each embodiment will be described based on this example of the common configuration.

[0018] As shown in FIG. 1, the culture device 10 according to the technology of the present disclosure cultures hydrogen-oxidizing bacteria, which are microorganisms, as an example of a culture target. The raw material for growing the hydrogen-oxidizing bacteria is hydrogen (H ２ ), oxygen (O ２ ) and carbon dioxide (CO ２ ), as well as inorganic components such as ammonium sulfate. Hydrogen is an example of a flammable gas. The culture device 10 supplies a raw material gas to the culture solution to grow hydrogen-oxidizing bacteria in the culture solution. Furthermore, in the culture solution, the hydrogen-oxidizing bacteria efficiently produce organic substances such as alcohol and amino acids by modifying the genes of the hydrogen-oxidizing bacteria. The culture solution is purified to extract the organic substances produced in the culture solution. The extracted organic substances are used, for example, in the production of chemical products or bioproducts. Furthermore, hydrogen-oxidizing bacteria are separated from the culture solution, and the isolated hydrogen-oxidizing bacteria are being considered for use as, for example, feed, food, and fuel.

[0019] As shown in FIG. 2 , the culture device 10 includes a culture tank 11, a raw material gas tank 12, a culture solution tank 13, an adjustment gas tank 14, a culture target tank 15, and a processor 17. The culture tank 11 contains a culture solution 18. Examples of the hydrogen-oxidizing bacteria 21 include bacteria of the genus Hydrogenophilus, as described in Japanese Patent No. 6528295. In this case, as described in Japanese Patent No. 6528295, for example, the culture solution 18 may contain ammonium sulfate ((NH ４ ) ２ SO ４ ), potassium dihydrogen phosphate (KH ２ P.O. ４ ), dipotassium hydrogen phosphate (K ２ HPO４ ), sodium chloride (NaCl), or the like is dissolved in water. The culture tank 11 is an example of a "culture tank" according to the technology of the present disclosure. Note that, instead of or in addition to the raw material gas tank 12, a gas generator that generates raw material gas 26 may be provided.

[0020] The culture tank 11 is connected to supply paths 12A, 13A, 14A, and 15A, respectively, for a raw material gas tank 12, a culture solution tank 13, an adjustment gas tank 14, and a culture target tank 15. Each of the supply paths 12A, 13A, 14A, and 15A is composed of piping, valves, etc. A pump 22 and a flow meter 23 for measuring the flow rate of the fluid flowing through each supply path are disposed in each of the supply paths 12A, 13A, 14A, and 15A.

[0021] The culture solution tank 13 contains a culture solution 18. The culture solution 18 is supplied from the culture solution tank 13 to the culture tank 11 through the supply path 13A by driving a pump 22 on the supply path 13A. The supply timing and supply amount of the culture solution 18 are controlled by a processor 17 that controls the driving of the pump 22.

[0022] (Pretreatment of culture solution in culture solution tank) As an example, the culture solution tank 13 is provided with a degassing device 13B. The degassing device 13B removes unwanted gases dissolved in the culture solution 18 when refilling the culture tank 11 with the culture solution 18 from the culture solution tank 13. Unwanted gases are gases such as air and nitrogen that have an adverse effect on the culture (such as reducing the culture efficiency).

[0023] The culture solution tank 13 and the raw material gas tank 12 may be connected by piping or the like so that the raw material gas can be replenished to the culture solution 18 before it is supplied to the culture tank 11. By preliminarily replenishing the culture solution 18 with the raw material gas before it is supplied to the culture tank 11, the dissolved gas concentration of the raw material gas in the culture solution 18 to be supplied to the culture tank 11 can be improved. This may improve the culture efficiency. In this case, the culture solution tank 13 may be provided with a dissolved gas concentration measuring unit (similar to the dissolved gas concentration measuring unit 49 described below) that measures the dissolved gas concentration of the raw material gas in the culture solution 18, and the amount of raw material gas replenished may be controlled according to the measured dissolved gas concentration.

[0024] The culture target tank 15 contains hydrogen-oxidizing bacteria 21, which are an example of a culture target. The hydrogen-oxidizing bacteria 21 are supplied from the culture target tank 15 to the culture tank 11 through the supply path 15A by driving a pump 22 on the supply path 15A. The supply timing and supply amount of the hydrogen-oxidizing bacteria 21 are controlled by a processor 17 that controls the driving of the pump 22.

[0025] The source gas tank 12 contains a source gas 26. As described above, the source gas 26 may be, for example, hydrogen (H ２ ), oxygen (O ２ ) and carbon dioxide (CO ２ The raw material gas 26 is a gas containing various components such as ammonium nitrate, ammonium nitrate, ammonium nitrate, and ammonium nitrate. The raw material gas 26 is supplied from the raw material gas tank 12 to the culture tank 11 through the supply path 12A by driving a pump 22 on the supply path 12A. The supply timing and supply amount of the raw material gas 26 are controlled by a processor 17 that controls the driving of the pump 22.

[0026] The downstream end of the supply path 12A is disposed within the culture tank 11, and a sparger 28 is provided at the downstream end. The sparger 28 is used to disperse and supply the raw material gas 26 into the culture solution 18. As an example of the sparger 28, an aeration pipe formed of a porous material is used. The sparger 28 is an example of a bubble generator that generates the raw material gas 26 as bubbles within the culture solution 18. There are various types of bubble generators, including micropore types such as the sparger 28, swirling liquid flow types that generate bubbles by a high-speed swirling flow, ejector types (also called Venturi types) that generate bubbles by a sudden pressure change in the gas-liquid flow path, and static mixer types that generate bubbles by the shear force of an obstacle in the gas-liquid flow path. Types other than the sparger 28 may also be used as the bubble generator.

[0027] A portion of the raw material gas 26 supplied into the culture solution 18 is dissolved in the culture solution 18. The dissolved raw material gas 26 is taken up by the hydrogen-oxidizing bacteria 21 and consumed for the growth of the hydrogen-oxidizing bacteria 21 or the production of organic substances 29. The organic substances 29 are, for example, alcohols or amino acids. The raw material gas 26 that is not dissolved in the culture solution 18 is released into a space 11A present above a liquid surface 18A of the culture solution 18. The space 11A is filled with a mixed gas 31 that is the raw material gas 26 that is released without being dissolved in the culture solution 18. The raw material gas tank 12 and the pump 22 on the supply path 12A are an example of a "raw material gas supply unit."

[0028] The adjustment gas tank 14 contains an adjustment gas 33. The adjustment gas 33 is supplied from the adjustment gas tank 14 to the space 11A of the culture tank 11 through the supply path 14A by driving a pump 22 on the supply path 14A. The supply timing and supply amount of the adjustment gas 33 are controlled by a processor 17 that controls the operation of the pump 22. The mixed gas 31 in the space 11A contains hydrogen and oxygen, which are components of the raw material gas 26. Hydrogen is a flammable gas. As will be described later, the adjustment gas 33 is used to maintain the composition ratio of the mixed gas 31 in the space 11A at a predetermined target value outside the explosive range.

[0029] Furthermore, the mixed gas 31 contains components of the raw material gas 26. Therefore, a portion of the mixed gas 31 can be returned to the culture tank 11 via a gas circulation path 39 and reused as the raw material gas 26. The mixed gas 31 reused as the raw material gas 26 is also supplied to the culture tank 11 via a sparger 28. The mixed gas 31 that is not reused is discharged. Although not shown in the figure, when discharging the mixed gas 31 that is not reused, the mixed gas 31 is diluted with an inert gas such as carbon dioxide and then released to the atmosphere.

[0030] An exhaust line 36 for extracting the mixed gas 31 is connected to the culture tank 11, and the exhaust line 36 is provided with a pump 22 and a three-way valve 38. The pump 22 generates pressure for discharging and circulating the mixed gas 31. The three-way valve 38 switches between a state in which the exhaust line 36 is connected to a gas circulation line 39 and a state in which the exhaust line 36 is disconnected from the gas circulation line 39. The three-way valve 38 switches between sending the mixed gas 31 to the gas circulation line 39 or exhausting it to the outside. The exhaust line 36 is also provided with a composition ratio measurement unit 16 that measures the composition ratio of the mixed gas 31. The composition ratio measurement unit 16 is used to control the composition ratio of the mixed gas 31, which will be described later.

[0031] (Position of Mixed Gas Outlet) The mixed gas outlet 34, which extracts the mixed gas 31 from the culture tank 11, is positioned so that it can take in the foam layer 18B formed on the liquid surface 18A of the culture solution 18 in the culture tank 11. The foam layer 18B functions as a liquid film covering the liquid surface 18A and contributes to preventing explosions by increasing the heat capacity of the space 11A. However, the foam layer 18B may adversely affect various sensors and the like disposed in the culture tank 11, and may also damage the hydrogen-oxidizing bacteria 21 and the like. Therefore, by placing the mixed gas outlet 34 at a position where it can take in the foam layer 18B, it becomes possible to recover a portion of the foam layer 18B when extracting the mixed gas 31, thereby reducing the adverse effects caused by the foam layer 18B.

[0032] (Supply of each component of raw material gas) In addition, in FIG. 2, for the sake of convenience in order to prevent the drawing from becoming too complicated, the supply path 12A of the raw material gas 26 and the gas circulation path 39 of the mixed gas 31 are shown as one line. However, in reality, as shown in FIG. 3, the supply path 12A and the gas circulation path 39 are separated for each component such as hydrogen, oxygen, and carbon dioxide, making it possible to supply a plurality of components individually. Each supply path 12A and gas circulation path 39 for each component is provided with a pump 22 and a flow meter 23. In addition, the sparger 28 also supplies hydrogen (H ２ ), oxygen (O ２ ) and carbon dioxide (CO ２ Each of the supply paths 12A and gas circulation paths 39 for each component is connected to a sparger 28 corresponding to each component.

[0033] (Removal of impurities from raw material gas) The connecting member 40 connects the supply channel 12A and the gas circulation path 39 upstream of the spargers 28 for each component. As a result, the supply channel 12A and the gas circulation path 39 are integrated into one and connected to the sparger 28. An impurity removal mechanism 51 is provided between each connecting member 40 and each sparger 28. The impurity removal mechanism 51 removes impurities from the raw material gas 26 supplied to the culture tank 11. The impurities include sulfur oxides or nitrogen oxides (NO and NO), ２ The impurity removal mechanism 51 is a mechanism that uses any one of membrane separation, cryogenic separation, physical adsorption, and chemical absorption as a method for separating impurities from the source gas 26.

[0034] In FIG. 2 , impurities accumulate in the culture tank 11 as the culture treatment continues. As described below, a portion of the culture solution 18 in the culture tank 11 is temporarily removed and returned to the culture tank 11 for reuse. When the culture solution 18 is circulated, a raw material gas 26 is separated from the culture solution 18, and the raw material gas 26 in the culture solution 18 is also returned to the culture tank 11 via a gas reuse path 62 for reuse. A portion of the mixed gas 31 is also returned to the culture tank 11 via a gas circulation path 39 for reuse. The gas reuse path 62 and the gas circulation path 39 are connected upstream of an impurity removal mechanism 51. The reused mixed gas 31 and the separated gas separated from the culture solution 18 are resupplied into the culture tank 11 after impurities are removed by the impurity removal mechanism 51. Since impurities are removed while the raw material gas 26 is circulated in this manner, accumulation of impurities in the culture tank 11 can be suppressed.

[0035] (Separation of Components Contained in Mixed Gas) Furthermore, since the mixed gas 31 is a mixture of components such as hydrogen, oxygen, and carbon dioxide, the gas circulation path 39 is provided with a component separation mechanism 52 that separates each component contained in the mixed gas 31. The component separation mechanism 52 separates each component contained in the mixed gas 31, and the separated components are supplied to the gas circulation paths 39 provided for each component. The component separation mechanism 52 is a mechanism that uses any of membrane separation, cryogenic separation, physical adsorption, and chemical absorption as a method for separating each component from the mixed gas 31. The component separation mechanism 52 is an example of a "first component separation mechanism" according to the technology of the present disclosure.

[0036] In this way, when the raw material gas 26 is supplied to the culture tank 11, hydrogen (H ２ ), oxygen (O ２ ) and carbon dioxide (CO ２) are supplied separately, which has advantages in terms of culture efficiency and safety. The advantage in terms of culture efficiency is that the raw material gas 26 supplied to the culture tank 11 can be easily adjusted to an appropriate composition from the viewpoint of culture efficiency. The advantage in terms of safety is as follows. That is, the three elements of an explosion are a flammable gas, oxygen, and an ignition source. However, before supplying the raw material gas 26 to the culture tank 11, it is possible to handle the flammable gases hydrogen and oxygen, which are among the three elements of an explosion, separately, thereby further reducing the risk of explosion.

[0037] In addition to hydrogen, oxygen, and carbon dioxide, the component separation mechanism 52 may separate components such as nitrogen and methane from the mixed gas 31. Nitrogen, methane, and the like have the effect of reducing the solubility of the source gas 26 in the culture solution 18, and therefore, by separating these components when reusing the mixed gas 31, the solubility of the source gas 26 can be improved.

[0038] (Circulation, Recovery, and Reuse of Culture Solution) As shown in FIG. 4 in addition to FIG. 2 , a culture solution circulation path 54 is connected to the culture tank 11, and a culture solution recovery mechanism 55 is provided in the culture solution circulation path 54. The culture solution circulation path 54 removes a portion of the culture solution 18 from the culture tank 11. The culture solution recovery mechanism 55 recovers the culture solution 18 containing the organic substances 29 from the culture solution 18 removed from the culture tank 11 through the culture solution circulation path 54. The culture solution circulation path 54 returns the remaining culture solution 18 after recovery by the culture solution recovery mechanism 55, that is, the culture solution 18 containing the hydrogen-oxidizing bacteria 21, to the culture tank 11. When the grown hydrogen-oxidizing bacteria 21 are purified, the hydrogen-oxidizing bacteria 21 are recovered, for example, by a method different from that for recovering the organic substances 29.

[0039] (Separation of Dissolved Gas Contained in Culture Solution) In the culture solution circulation path 54, a gas separation mechanism 61 is provided downstream of the culture solution recovery mechanism 55. Before returning the culture solution 18 to the culture tank 11, the gas separation mechanism 61 separates a gas containing components of the raw material gas 26 contained in the culture solution 18 from the culture solution 18 as a separated gas. The culture solution 18 from which the separated gas has been separated is then returned to the culture tank 11. The gas separation mechanism 61 is a separation mechanism that uses any of membrane separation, cryogenic separation, physical adsorption, and chemical absorption. A hydrogen storage alloy may be used to separate hydrogen.

[0040] (Recycling of raw material gas from culture solution) A part of the separated gas separated by the gas separation mechanism 61 is returned to the culture tank 11 via the gas recycling path 62 and the gas circulation path 39 for the mixed gas 31. Then, the separated gas is reused as the raw material gas 26. This improves the utilization efficiency of the raw material gas 26.

[0041] (Suppression of explosion when reusing raw material gas from culture solution) Furthermore, since the separated gas is returned to the culture tank 11 via the gas circulation path 39, as described above, it is separated into components such as hydrogen, oxygen, and carbon dioxide by the component separation mechanism 52. However, instead of separating the separated gas into components in the component separation mechanism 52, the separated gas may be separated into components such as hydrogen, oxygen, and carbon dioxide in the gas reuse path 62. These separated components are reused via gas circulation paths 39 provided for each component. Separation of the separated gas into components in the gas reuse path 62 may be performed by, for example, the gas separation mechanism 61 that separates gas from the culture solution 18.

[0042] In this way, when the separated gas is reused, the flammable gases hydrogen and oxygen can be separated, thereby improving safety within the gas reuse path 62. From the viewpoint of safety, it is preferable to separate the flammable gas hydrogen from the culture solution 18 removed from the culture tank 11 as upstream as possible. Furthermore, it is preferable to separate the components first, followed by separating oxygen and carbon dioxide. Such a gas separation mechanism 61 has the function of suppressing explosions and is therefore an example of an "explosion suppression mechanism" according to the technology of the present disclosure.

[0043] Furthermore, by separating the components of the separated gas in the gas separation mechanism 61 in this manner, it is possible to reuse carbon dioxide as the raw material gas 26, or to return the carbon dioxide to the adjustment gas tank 14 and reuse it as the adjustment gas 33. When the gas separation mechanism 61 separates the separated gas into its components, it is also an example of a "second component separation mechanism" according to the technology of the present disclosure. As with the component separation mechanism 52, the gas separation mechanism 61 may separate components that reduce the solubility of the raw material gas 26, such as nitrogen and methane, in addition to hydrogen, oxygen, and carbon dioxide.

[0044] (Separation of specific components from culture solution) Furthermore, as shown in FIG. 5 , by using a separation mechanism 65 similar to the gas separation mechanism 61 and the component separation mechanism 52, in addition to separating gas from the culture solution 18, specific components contained in the culture solution 18 may be separated. Examples of specific components include ammonia and ammonium compounds. Ammonia and ammonium compounds serve as nutrient sources for the hydrogen-oxidizing bacteria 21. By separating these, the separated specific components can be reused while adjusting the supply amount.

[0045] In this way, by separating the various components contained in the mixed gas 31 and the culture solution 18, it is possible to remove unnecessary components and reuse those that can be used, thereby improving the culture efficiency and the utilization efficiency of the raw material gas 26.

[0046] 4, the culture medium recovery mechanism 55 is connected to a recovery liquid tank 57 that stores a recovery liquid 58, which is the recovered culture medium 18, via a recovery path 56. The recovery liquid 58 is transferred from the culture medium recovery mechanism 55 to the recovery liquid tank 57 through the recovery path 56. The recovery path 56 is provided with a pump 22 for transferring the recovery liquid 58.

[0047] A portion of the recovered liquid 58 stored in the recovered liquid tank 57 is transferred to a refinery device (not shown). In the refinery device, organic substances 29 produced by the cultivation of the hydrogen-oxidizing bacteria 21 are extracted from the recovered liquid 58.

[0048] (Process for reducing the dissolved flammable gas concentration in the recovered liquid) The culture device 10 is equipped with a concentration reduction mechanism that reduces the dissolved hydrogen concentration in the recovered liquid 58 to a level lower than that of the culture liquid 18 in the culture tank 11. The concentration reduction mechanism, for example, is configured by extending the overall length L of the section in the culture liquid circulation path 54 from the culture tank 11 to the culture liquid recovery mechanism 55 to a length necessary for reducing the concentration. Specifically, the overall length L of this section is a length necessary for reducing the dissolved hydrogen concentration in the recovered liquid 58 to 1 / 10 or less of the dissolved hydrogen concentration in the culture liquid 18 in the culture tank 11. The culture liquid 18 removed from the culture tank 11 contains hydrogen-oxidizing bacteria 21 that consume hydrogen, and the hydrogen-oxidizing bacteria 21 also consume hydrogen in the culture liquid circulation path 54. The longer the culture liquid circulation path 54, the more time is ensured for hydrogen to be consumed by the hydrogen-oxidizing bacteria 21. This improves the hydrogen utilization efficiency. Furthermore, if hydrogen is consumed in the section of the culture solution circulation path 54 up to the culture solution recovery mechanism 55, the dissolved hydrogen concentration in the recovery solution 58 recovered by the culture solution recovery mechanism 55 will decrease. This will also reduce the amount of hydrogen released from the recovery solution 58, thereby reducing the risk of explosion in the recovery solution tank 57 and ensuring safety. The culture solution circulation path 54, in which the total length L of the above section is the length necessary for concentration reduction, is an example of a "concentration reduction mechanism" according to the technology of the present disclosure.

[0049] Alternatively, instead of extending the overall length L of the section of the culture solution circulation path 54, the flow rate of the culture solution 18 flowing through the section may be reduced. This extends the time until the culture solution 18 removed from the culture tank 11 is transferred to the culture solution recovery mechanism 55, thereby extending the time during which hydrogen is consumed in the removed culture solution 18. As a result, the same effect as when the overall length L of the section is extended can be obtained. The flow rate of the culture solution 18 can be adjusted, for example, by controlling the amount of suction per unit time of the pump 22. The amount of suction by the pump 22 is controlled by the processor 17. Such a flow rate adjustment mechanism constituted by the processor 17 and the pump 22 is also an example of a "concentration reduction mechanism" according to the technology of the present disclosure.

[0050] (Downstream Side of Recovery Liquid Tank 57) A purification target separation mechanism 59 is provided downstream of the recovery liquid tank 57. The purification target separation mechanism 59 separates a portion of the recovery liquid 58 containing the organic substances 29 from the recovery liquid 58 as a purification target and sends the separated purification target to a purification device. The remaining recovery liquid 58 other than the recovery liquid 58 separated as a purification target by the purification target separation mechanism 59 is returned to the culture tank 11 as the culture liquid 18 via the liquid reuse path 63 and the culture liquid circulation path 54 for reuse.

[0051] As shown in an enlarged view of a portion of the culture solution recovery mechanism 55 in Fig. 4, the culture solution recovery mechanism 55 includes a pump 22 and a liquid separation mechanism 64. The pump 22 generates a circulation pressure for circulating the culture solution 18. Similar to the purification target separation mechanism 59, the liquid separation mechanism 64 separates a portion of the culture solution 18 containing organic substances 29 from the culture solution 18 removed from the culture tank 11, and sends the separated culture solution 18 to the recovery path 56 as a recovered liquid 58. The remaining culture solution 18 is sent to the gas separation mechanism 61.

[0052] (Position of culture solution outlet in culture solution circulation path) As shown in FIG. 6 , the culture solution circulation path 54 has an outlet 54A for extracting the culture solution 18 from the culture tank 11 and a return port 54B for returning a portion of the extracted culture solution 18 to the culture tank 11. The culture solution 18 in the culture tank 11 has a low dissolved gas concentration of the raw material gas 26 at the upper side in the height direction and a high dissolved gas concentration at the lower side. The outlet 54A is set in a low-concentration region where the dissolved gas concentration is relatively low, and the return port 54B is set in a high-concentration region where the dissolved gas concentration is relatively high. More specifically, the outlet 54A is set in a low-concentration region where the dissolved gas concentration of the culture solution 18 in the culture tank 11 is lower than the average value Av.

[0053] This makes it easier to eliminate unevenness in the dissolved gas concentration of the culture solution 18 in the culture tank 11 when a portion of the culture solution 18 is removed from the culture tank 11 to circulate the culture solution 18.

[0054] 2, the culture tank 11 is provided with a stirring rod 41 that stirs the culture solution 18. The stirring rod 41 has a support rod with a screw 41A attached thereto, and the screw 41A is disposed within the culture solution 18. The stirring rod 41 rotates around the support rod as a rotation axis by driving a motor 42 controlled by the processor 17. This stirs the culture solution 18. By stirring the culture solution 18, the stirring rod 41 diffuses the hydrogen-oxidizing bacteria 21 and the raw material gas 26 in the culture solution 18 without causing localized unevenness.

[0055] Furthermore, the stirring rod 41 stirs the culture solution 18 to create bubbles in the culture solution 18, forming the foam layer 18B on the liquid surface 18A of the culture solution 18.

[0056] In addition, the culture tank 11 is provided with a thermometer 46, a temperature regulator 47, a pressure gauge 48, a dissolved gas concentration measurement unit 49, and a density measurement unit 50. The thermometer 46 measures the temperature T in the culture solution 18. The temperature regulator 47 heats or cools the culture solution 18 in the culture tank 11. The pressure gauge 48 measures the pressure PS in the space 11A. The dissolved gas concentration measurement unit 49 measures the dissolved gas concentration Dr of the raw material gas 26 dissolved in the culture solution 18. The density measurement unit 50 measures the density ρ of the hydrogen-oxidizing bacteria 21 present in the culture solution 18 in the culture tank 11.

[0057] The culture solution 18 is maintained at a target temperature suitable for culturing the hydrogen-oxidizing bacteria 21. For example, the target temperature is between 40°C and 95°C. The target temperature is set for each microorganism. When the hydrogen-oxidizing bacteria 21 are of the genus Hydrogenophilus, the target temperature is preferably around 50°C. The culture solution 18 is heated to reach the target temperature, and may also need to be cooled. This is because the cultured microorganisms may generate heat during growth, causing the culture solution 18 to exceed the target temperature. Based on the temperature T measured by the thermometer 46, the processor 17 controls the operation of the temperature regulator 47 so that the temperature T of the culture solution 18 is maintained at the target temperature.

[0058] The processor 17 also controls the pressure of the mixed gas 31 in the space 11A based on the pressure PS measured by the pressure gauge 48. Setting the pressure PS of the mixed gas 31 to a target pressure improves the solubility of the source gas 26 in the culture solution 18. In this way, the processor 17 controls the pressure of the mixed gas 31 to ensure appropriate solubility in the culture solution 18, thereby improving the cultivation efficiency of the hydrogen-oxidizing bacteria 21. The pressure PS of the mixed gas 31 is adjusted to at least one of the supply amount of the source gas 26, the discharge amount of the mixed gas 31, and the supply amount of the adjustment gas 33. The processor 17 adjusts the supply amount or discharge amount of these gases by controlling the operation of each pump 22.

[0059] More specifically, the dissolved gas concentration measurement unit 49 measures the concentration of each component (hydrogen, oxygen, and carbon dioxide) contained in the source gas 26 dissolved in the culture solution 18. The dissolved gas concentration measurement unit 49 is, for example, composed of a dissolved hydrogen meter (e.g., model KM2100DH manufactured by Kyoei Electronics Laboratory) that measures the dissolved hydrogen concentration (Dr(H)), a dissolved oxygen meter (e.g., model InPro6860i manufactured by METTLE TOLEDO) that measures the dissolved oxygen concentration (Dr(O)), and a dissolved carbon dioxide meter (e.g., model InPro5000i manufactured by METTLE TOLEDO) that measures the dissolved carbon dioxide concentration (Dr(CO)). The dissolved gas concentration measurement unit 49 outputs the measurement values ​​to the processor 17.

[0060] 3, the source gas tank 12 accommodates each component (hydrogen, oxygen, carbon dioxide) of the source gas 26. A supply path 12A and a pump 22 are provided for each component.

[0061] The processor 17 acquires the measured value of the dissolved gas concentration for each component from the dissolved gas concentration measuring unit 49, compares the dissolved gas concentration for each component with a target value, and supplies any component that is lacking in the raw material gas 26 to the culture tank 11. By controlling the supply amount of each component of the raw material gas 26 in this way, the processor 17 can maintain the dissolved gas concentration of the raw material gas 26 in the culture solution 18 at an appropriate value.

[0062] The density measurement unit 50 measures the density ρ of the culture target present in the culture solution 18 in the culture tank 11. The density measurement unit 50 is configured, for example, with a total cell density sensor (for example, model Dencytee RS485 manufactured by HAMILTON). In this example, the culture target is hydrogen-oxidizing bacteria 21, so the density measurement unit 50 measures the density ρ of the hydrogen-oxidizing bacteria 21 in the culture solution 18. The density ρ of the hydrogen-oxidizing bacteria 21 has a positive correlation with the consumption amount of the raw material gas 26 consumed by the hydrogen-oxidizing bacteria 21. Measuring the density ρ can be used, for example, to calculate the consumption amount of the raw material gas 26 consumed by the hydrogen-oxidizing bacteria 21, or can be used for process checks to verify whether the consumption amount of the raw material gas 26 is appropriate for the amount of the hydrogen-oxidizing bacteria 21.

[0063] The water level meter 66 measures the water level of the culture solution 18 in the culture tank 11, i.e., the height of the liquid surface 18A. The amount of the culture solution 18 present in the culture tank 11 can be determined from the water level of the culture solution 18 measured by the water level meter 66. The water level meter 66 is used for process checks to determine whether the amount of the culture solution 18 is appropriate, and for calculating the necessary amount of replenishment of the culture solution 18.

[0064] The culture tank 11 is also provided with an explosion vent 67. The explosion vent 67 is configured to be destroyed before other parts in the event of an explosion inside the culture tank 11, thereby safely releasing the pressure inside the culture tank 11 and preventing the spread of damage. The vicinity of the explosion vent 67 is selected to be a location where no major damage will occur even if pressure is released, or a location where measures have been taken to prevent the damage from spreading.

[0065] The processor 17 is composed of, for example, a CPU (Central Processing Unit) and a RAM (Random Access Memory), and as described above, controls each part of the culture device 10. The memory 17A is a non-volatile memory, such as a flash memory, in which various setting information is stored.

[0066] (Control of bubble diameter of raw gas supplied to culture tank) The bubble diameter of the raw gas 26 generated in the culture solution 18 of the culture tank 11, d90, is set to 1000 μm or less. As shown in FIG. 7, d90 refers to the bubble diameter at which the cumulative volume of all bubbles, when the volumes of all bubbles are added up in ascending order from smallest to largest, is 90% of the total volume of all bubbles. The mountain-shaped distribution in the bar graph shown in FIG. 7 is a histogram of the bubble diameters of bubbles generated in the culture solution 18, with the horizontal axis representing bubble diameter and the vertical axis representing frequency. Accumulating the volumes of such bubble diameters results in a line graph with an upward slope as shown in FIG. 7. d90 is the bubble diameter at which the cumulative volume ratio is 90% of the total volume. In the culture apparatus 10, for example, this bubble diameter is set to 1000 μm or less. Such a bubble diameter is determined, for example, by the specifications of a bubble generator such as a sparger 28. Regarding the bubble diameter, by setting d90 to 1000 μm or less, the solubility of the source gas 26 in the culture solution 18 can be improved. A more preferable bubble diameter is d90 of 500 μm or less, and a more preferable bubble diameter is d90 of 200 μm or less. By setting the bubble diameter to such a value, high solubility of the source gas 26 can be ensured even under conditions in which the source gas 26 is difficult to dissolve, such as when the temperature of the culture solution 18 is high or the depth of the culture tank 11 is shallow.

[0067] (Surface Tension Reducer) As shown in FIG. 8 , the culture solution 18 may contain a surface tension reducer by adding the surface tension reducer. When the surface tension of the culture solution 18 is reduced, the bubbles tend to be smaller in diameter, thereby improving the solubility of the source gas 26 containing hydrogen, a flammable gas. The surface tension of the culture solution 18 is preferably 65 mN / m or less. A surface tension of this level makes it easier to achieve a bubble diameter d90 of 1000 μm or less. The amount of surface tension reducer added is determined so that the surface tension is this value. The surface tension of the culture solution 18 is more preferably 55 mN / m or less, and even more preferably 45 mN / m or less. By achieving such a surface tension, the bubble diameter tends to be smaller.

[0068] (Reuse of waste gas) Furthermore, as shown in Figure 9, the culture device 10 may reuse waste gas containing carbon dioxide discharged from an external device as the raw material gas 26 for the culture device 10. The external device is a device other than the culture device 10, and may be, for example, another device in the same facility where the culture device 10 operates, or another device in another facility (such as a factory). When the waste gas is reused, carbon dioxide is separated from the waste gas by a component separation mechanism 52, and the separated carbon dioxide is reused as the raw material gas 26. Reusing the carbon dioxide contained in the waste gas in this way can contribute to reducing carbon dioxide emissions.

[0069] 2. First Embodiment Based on the above example of the common configuration, a first embodiment of the culture device 10 will be described with reference to Figures 10 to 16. The culture device 10 of the first embodiment controls the composition ratio of the mixed gas 31, and the dissolution rate and consumption rate of hydrogen as a safety measure when using hydrogen, which is a flammable gas.

[0070] 10, measurement signals and detection signals from various sensors of the culture device 10 are input to the processor 17. Target values ​​for various controls are stored as culture condition information in the memory 17A of the processor 17. The processor 17 performs various controls by outputting control signals to each section according to the target values.

[0071] The target values ​​for various controls include the target temperature and target pressure of the culture solution 18. Furthermore, examples of target values ​​outside the explosive range used for controlling the composition ratio include the target value of the hydrogen concentration (TD(H)), the target value of the oxygen concentration (TD(O)), and the water vapor concentration (not shown). Additionally, the memory 17A stores the target value of the hydrogen dissolution rate (TRd(H)) used for controlling the hydrogen dissolution rate, and the target value of the hydrogen consumption rate (TRc(H)) used for controlling the hydrogen consumption rate.

[0072] (Control of Composition Ratio of Mixed Gas) As described above, hydrogen is a flammable gas, and the adjustment gas 33 is used to maintain the composition ratio of the mixed gas 31 in the space 11A at a predetermined target value outside the explosive range. In the mixed gas 31, hydrogen, which is a flammable gas, is mixed with oxygen. In this case, an explosion may occur depending on the composition ratio of the mixed gas 31. The composition ratio of the mixed gas at which an explosion occurs is called the explosive range. As described above, the memory 17A of the processor 17 stores target values ​​outside the explosive range, such as the target hydrogen concentration (TD(H)), the target oxygen concentration (TD(O)), and the water vapor concentration. The target value outside the explosive range varies depending on the components of the mixed gas 31. In the present example, when the mixed gas 31 contains hydrogen and oxygen, the target value outside the explosive range is generally an oxygen concentration of less than 5% or a hydrogen concentration of less than 4% in the mixed gas 31.

[0073] Furthermore, the applicant has experimentally verified that the composition ratio of the mixed gas can be maintained outside the explosive range even when the oxygen concentration is 5% or more, as long as the water vapor concentration is 7% or more. Therefore, in this example, the target value outside the explosive range is set, for example, to a range of 5% to 9% for the oxygen concentration when the water vapor concentration is 7% to 90%.

[0074] The experiment was conducted as follows. A stainless steel chamber with an inner diameter of 200 mm, a depth of 200 mm, and a volume of 6 L was used as the explosion vessel. Hydrogen, oxygen, carbon dioxide, and water vapor were filled into the explosion vessel. (Water vapor was produced by pouring water into the explosion vessel and evacuating it to the saturated water vapor pressure at the temperature inside the vessel, thereby vaporizing the water. Hydrogen, oxygen, and carbon dioxide were filled from gas cylinders through gas inlet pipes attached to the explosion vessel.) After homogenizing the gas by turning on the stirring fan inside the explosion vessel, ignition of the gas was attempted using a thin wire explosion device attached to the explosion vessel. Ignition or non-ignition was determined based on the presence or absence of pressure increase and the presence or absence of negative pressure inside the explosion vessel due to the generation of water. Pressure was measured using a pressure sensor (Kyowa Electric Industry, PHS-B-10MP) attached to the upper valve of the gas exhaust pipe attached to the explosion vessel.

[0075] Table 1 shows the experimental results of whether or not ignition occurs depending on the gas concentration of the mixed gas. Example 1 and Comparative Example 1 in Table 1 are both examples where the water vapor concentration is 0%, and the concentrations other than the oxygen concentration are almost the same. In Example 1, where ignition did not occur, the oxygen concentration was 4%, less than 5%, while in Comparative Example 1, where ignition occurred, the oxygen concentration was 9%, greater than 5%. Example 1 and Comparative Example 1 show experimental results that, as is generally known, when the water vapor concentration is 0%, ignition will not occur if the oxygen concentration is less than 5%.

[0076] Furthermore, Examples 2, 3, and Comparative Example 2 all have a water vapor concentration of 7% or higher, with only the oxygen concentration being significantly different. Examples 2 and 3 have an oxygen concentration of 9%, while Comparative Example 2 has an oxygen concentration of 16%, which is higher than 9%. These experimental results show that when the water vapor concentration is 7% or higher, ignition does not occur as long as the oxygen concentration is 5% or higher but 9% or lower.

[0077]

[0078] Although Table 1 does not include experimental results for hydrogen concentrations less than 4%, it is known that if the hydrogen concentration is less than 4% instead of the oxygen concentration being less than 5%, the mixed gas will not ignite even when the water vapor concentration is 0%. Therefore, as a target value outside the explosive range, the hydrogen concentration of mixed gas 31 may be less than 4% instead of the oxygen concentration of mixed gas 31 being less than 5%.

[0079] The adjustment gas 33 is, for example, an inert gas. More specifically, in this example, carbon dioxide (CO ２ ) is used. By supplying the adjustment gas 33 to the space 11A, the oxygen concentration or hydrogen concentration decreases, and the composition ratio of the mixed gas 31 is maintained at a target value outside the explosive range. Note that any gas other than an inert gas can be used as the adjustment gas 33. For example, any gas may be used as the adjustment gas 33 to set the oxygen concentration of the mixed gas 31 to less than 5%, thereby setting the composition ratio of the mixed gas 31 to a target value outside the explosive range. In this way, any gas can be used as the adjustment gas 33. However, as described above, when the mixed gas 31 is reused, it is preferable to use the components of the raw material gas 26 as the adjustment gas 33.

[0080] As shown in FIG. 11 , the composition ratio measurement unit 16 is disposed on an exhaust path 36 that exhausts the mixed gas 31 from the space 11A of the culture tank 11. The composition ratio measurement unit 16 measures, for example, the hydrogen concentration (D(H ２ A gas analyzer (e.g., Horiba Ltd. Model TCA-51d) measuring the oxygen concentration (D(O ２ A gas analyzer (e.g., Horiba Ltd. model number VA-5113) measuring the carbon dioxide concentration (D(CO ２ )) and a flow meter (for example, model number CMFS007M manufactured by Emerson) that measures the total flow rate (Qout(total)) of the mixed gas 31. This allows the composition ratio measurement unit 16 to measure the concentration of each component of the mixed gas 31 and the total flow rate. The composition ratio measurement unit 16 outputs each measurement value to the processor 17 as a measurement signal.

[0081] The processor 17 determines the supply amount of the adjustment gas 33 based on, for example, the total flow rate of the mixed gas 31 and the measured value of the oxygen concentration so that the oxygen concentration of the mixed gas 31 is maintained below a preset upper limit value. Then, the processor 17 controls the pump 22 to supply the determined supply amount of the adjustment gas 33 from the adjustment gas tank 14 to the space 11A. As a result, the supply amount of carbon dioxide (Qin(CO ２ )) increases, and the oxygen concentration (D(O ２ )) decreases, and the composition ratio of the mixed gas 31 in the space 11A reaches a preset target value (TD(O ２ By increasing the supply amount of the adjustment gas 33, the hydrogen concentration (D(H ２ )) also decreases, so the hydrogen concentration also reaches the target value outside the explosive range (TD(O ２ The processor 17, the adjustment gas tank 14, and the pump 22 on the supply line 14A are an example of a "composition ratio control mechanism" according to the technology of the present disclosure.

[0082] Furthermore, since both the culture solution 18 and the space 11A are present in the culture tank 11, by maintaining the temperature T of the culture solution 18 at a target temperature, the temperature in the space 11A can be maintained at approximately the same temperature. As will be described later, the composition ratio of the mixed gas 31 in the space 11A is maintained at a predetermined target value outside the explosion range. The target value also includes the water vapor concentration of the mixed gas 31. By controlling the temperature of the culture solution 18 to 40°C or higher, the temperature of the mixed gas 31 can be increased to 40°C or higher. This makes it possible to adjust the water vapor concentration of the mixed gas 31 to 7% or higher.

[0083] 12 , a dissolution rate control mechanism including a processor 17 executes hydrogen dissolution rate control as an example of flammable gas dissolution rate control. The processor 17, the composition ratio measurement unit 16, and the flow meter 23 are an example of a “dissolution rate control mechanism” according to the technology of the present disclosure.

[0084] The dissolution rate control mechanism measures the hydrogen dissolution rate, which is the proportion of hydrogen dissolved in the culture solution 18 among the hydrogen, a combustible gas contained in the raw material gas supplied to the culture tank 11 through the gas circulation path 39 or the raw material gas supply unit, during the culture, and maintains the measured hydrogen dissolution rate (Rd(H2)) at a preset target value (TRd(H2)) or higher. The hydrogen dissolution rate (Rd(H2)) is defined by the following formula (1), where Qout(H2) is the amount of hydrogen discharged from the culture tank 11 as the mixed gas 31, and Qin(H2) is the amount of hydrogen supplied to the culture tank 11. Rd(H2) (%) = (1 - Qout(H2) / Qin(H2)) × 100 ... formula (1)

[0085] In other words, the amount of hydrogen dissolved in the culture solution 18 is the amount of hydrogen supplied to the culture tank 11 minus the amount of hydrogen discharged from the culture tank 11, and the ratio of the amount of dissolved hydrogen to the amount of hydrogen supplied is the hydrogen dissolution rate.

[0086] Qout(H) is the value obtained by multiplying the total amount (Qout(total)) of the mixed gas 31 discharged from the culture tank 11 by the hydrogen concentration (D(H)) of the mixed gas 31. The processor 17 acquires Qin(H) from the flow meter 23, acquires Qout(total) and the hydrogen concentration (D(H)) from the composition ratio measurement unit 16, and measures the hydrogen dissolution rate (Rd(H)) based on the acquired measured values.

[0087] The processor 17 then controls, for example, the amount of hydrogen supplied (Qin(H2)) to the culture tank 11 so that the hydrogen dissolution rate (Rd(H2)) is maintained at or above the target value (TRd(H2)). By reducing the amount of hydrogen supplied to the culture tank 11, the hydrogen dissolution rate (Rd(H2)) can be increased according to the definition of formula (1). The target value of the hydrogen dissolution rate is preferably 90% or higher, for example.

[0088] Increasing the dissolution rate of hydrogen reduces the amount of hydrogen released into the space 11A. By controlling the dissolution rate in addition to the composition ratio control mechanism of the mixed gas 31, the hydrogen concentration of the mixed gas 31 can be further reduced, thereby reducing the risk of explosion and improving safety compared to conventional methods. Such control is an effective technique when using a source gas 26 containing a flammable gas such as hydrogen.

[0089] (Control of Combustible Gas Consumption Rate) Furthermore, as shown in FIG. 12, the dissolution rate control mechanism may control the hydrogen consumption rate through dissolution rate control.

[0090] Specifically, during the culture, the dissolution rate control mechanism measures the hydrogen consumption rate of the hydrogen consumed by the hydrogen-oxidizing bacteria 21 out of the combustible hydrogen contained in the raw material gas 26 supplied to the culture tank 11 through the gas circulation path 39 or the raw material gas supply unit, and maintains the measured hydrogen consumption rate (Rc(H)) at a target value (TRc(H)) of 90% or more by controlling the hydrogen dissolution rate.

[0091] The hydrogen consumption rate (Rc(H)) is defined by the following formula (2) where Qcs(H) is the amount of hydrogen consumed by the hydrogen-oxidizing bacteria 21 in the culture tank 11: Rc(H) (%) = Qcs(H) / Qin(H) × 100 (2)

[0092] In other words, the ratio of the amount of hydrogen consumed by the hydrogen-oxidizing bacteria 21 in the culture tank 11 to the amount of hydrogen supplied to the culture tank 11 is the hydrogen consumption rate.

[0093] The difference between Qin(H2), which is the amount of hydrogen supplied to the culture tank 11, and Qout(H2), which is the amount of hydrogen discharged from the culture tank 11, indicates the amount of hydrogen dissolved in the culture solution 18. The amount of hydrogen dissolved in the culture solution 18 includes Qcs(H2), which is the amount consumed by the hydrogen-oxidizing bacteria 21, as well as the amount of dissolved hydrogen that was dissolved in the culture solution 18 but remains unconsumed. Therefore, if the amount of dissolved hydrogen is Qr(H2), then Qcs(H2) = Qin(H2) - (Qout(H2) + Qr(H2)). Here, the amount of dissolved hydrogen Qr(H2) refers to the amount of change from the reference amount of dissolved hydrogen. For example, if Qcs(H2), Qin(H2), and Qout(H2) are the hydrogen consumption, hydrogen supply, and hydrogen discharge amounts per minute, respectively, the dissolved hydrogen amount Qr(H2) indicates the change from the dissolved hydrogen amount (amount of hydrogen dissolved in the culture solution 18) one minute ago.

[0094] If the capacity of the culture solution 18 contained in the culture tank 11 is Qm, the amount of dissolved hydrogen (Qr(H2)) can be calculated by multiplying the capacity of the culture solution 18 (Qm) by the dissolved hydrogen concentration (Dr(H2)). The processor 17 calculates the capacity of the culture solution 18 (Qm) based on the water level obtained from the water level gauge 66, and measures the amount of dissolved hydrogen (Qr(H2)) by obtaining the dissolved hydrogen concentration (Dr(H2)) measured from the dissolved gas concentration measurement unit 49. The processor 17 then measures the hydrogen consumption amount (Qcs(H2)) and the hydrogen consumption rate (Rc(H2)) according to equation (2).

[0095] The dissolution rate control mechanism including the processor 17 maintains the hydrogen consumption rate (Rc(H)) at a target value (TRc(H)) of 90% or more through dissolution rate control that reduces the amount of hydrogen supplied. By improving the hydrogen consumption rate, the utilization efficiency of the source gas 26 is improved.

[0096] The operation of the above configuration will be described with reference to the flowcharts shown in FIGS. 13 to 15 . FIG. 13 shows the procedure for the composition ratio control process. For example, with a culture solution 18 containing hydrogen-oxidizing bacteria 21 contained in the culture tank 11, the processor 17 drives the temperature regulator 47 to heat the culture solution 18 to a target temperature. After the culture solution 18 reaches the target temperature, the processor 17 starts the supply of the raw material gas 26, thereby initiating the culture process. Even after the culture process starts, the processor 17 continues to control the temperature of the culture solution 18 to the target temperature via the temperature regulator 47. During the culture process, the hydrogen-oxidizing bacteria 21 grow by absorbing the raw material gas 26 dissolved in the culture solution 18 and further produce organic substances 29. The hydrogen-oxidizing bacteria 21 efficiently produce the organic substances 29 by genetically modifying them. The hydrogen-oxidizing bacteria 21 produce the organic substances 29 during or after growth. A portion of the raw material gas 26 that is not dissolved in the culture solution 18 is released into the space 11A above the liquid surface 18A of the culture solution 18 and becomes a mixed gas 31.

[0097] In step S101 of the composition ratio control process, the processor 17 acquires, from the composition ratio measurement unit 16, measured values ​​of the concentration of each component of the mixed gas 31 and the total flow rate of the mixed gas 31. Then, the processor 17 calculates the oxygen concentration of the mixed gas 31 based on the acquired measured values, and acquires this as the composition ratio of the mixed gas 31.

[0098] In step S102, the processor 17 determines whether the composition ratio of the mixed gas 31 is outside the explosive range. As described above, in this example, the target values ​​for the explosive range are set to an oxygen concentration of 5% to 9% and a water vapor concentration of 7% or higher. Also, in this example, the target temperature of the culture solution 18 is set to 40°C or higher. Therefore, the saturated water vapor amount at 40°C is approximately 7% when converted to a water vapor concentration. Therefore, if the target temperature of the culture solution 18 is set to 40°C or higher, it is possible to adjust the water vapor concentration of the mixed gas 31 to 7% or higher. The processor 17 compares the oxygen concentration derived from the measurement value of the composition ratio measurement unit 16 with the target value. If the oxygen concentration is within the target range, the processor 17 determines that the composition ratio is outside the explosive range (Y in step S102) and proceeds to step S104.

[0099] On the other hand, if the oxygen concentration exceeds 9%, which is the upper limit of the target value, the processor 17 determines that the composition ratio of the mixed gas 31 is within the explosive range (N in step S102), and proceeds to step S103. In step S103, the processor 17 drives the pump 22 of the supply path 14A to supply the adjustment gas 33 to the space 11A. This reduces the oxygen concentration of the mixed gas 31, and the composition ratio of the mixed gas 31 can be returned to outside the explosive range.

[0100] The processor 17 repeats this composition ratio control process until the culture process is completed (Y in step S104), thereby maintaining the composition ratio of the mixed gas 31 in the space 11A at a target value outside the explosive range.

[0101] During the culture, the processor 17 executes the dissolution rate control process shown in FIG. First, in step S201, the processor 17 measures the hydrogen dissolution rate (Rd(H)) in the culture tank 11 according to equation (1). Then, in step S202, the processor 17 compares the measured hydrogen dissolution rate (Rd(H)) with the target value (TRd(H)) and determines whether the hydrogen dissolution rate (Rd(H)) is equal to or greater than the target value (TRd(H)). If the hydrogen dissolution rate (Rd(H)) is below the target value (TRd(H)) (N in step S202), the processor 17 proceeds to step S203 and reduces the hydrogen supply amount (Qin(H)). In step S203, the processor 17 maintains the hydrogen dissolution rate (Rd(H)) at or above the target value (TRd(H)). The processor 17 repeats this process until the culture process is completed (step S204).

[0102] Furthermore, the processor 17 executes the consumption rate control process shown in FIG. 15 through the dissolution rate control process. First, in step S301, the processor 17 measures the hydrogen consumption rate ((Rc(H)) in the culture tank 11 according to formula (2). Then, in step S302, the processor 17 compares the measured hydrogen consumption rate ((Rc(H))) with the target value (TRc(H)) to determine whether the hydrogen consumption rate ((Rc(H))) is equal to or greater than the target value (TRc(H)). If the hydrogen consumption rate ((Rc(H))) is lower than the target value (TRc(H)), If step S302 is negative (N), the processor 17 proceeds to step S303. In step S303, the processor 17 reduces the amount of hydrogen supplied (Qin(H2)), similar to step S203 of the dissolution rate control process. In step S303, the processor 17 maintains the hydrogen consumption rate (Rc(H2)) at or above the target value (TRc(H2)). The processor 17 repeats this process until the culture process is completed (step S304).

[0103] As described above, the culture apparatus 10 of the first embodiment according to the technology of the present disclosure includes a mechanism for controlling the composition ratio of the mixed gas 31 and a mechanism for controlling the dissolution rate of hydrogen (an example of a flammable gas). The composition ratio control mechanism maintains the composition ratio of the mixed gas 31 in the culture tank 11 at a target value outside the explosive range, thereby improving safety compared to conventional devices.

[0104] Furthermore, as shown in Figure 16, by controlling the dissolution rate, the dissolution rate of hydrogen in the culture solution 18 in the culture tank 11 is maintained at or above a target value, thereby reducing the amount of hydrogen released into the space 11A and the amount of hydrogen contained in the mixed gas 31. This further improves safety. Because the culture apparatus 10 of the first embodiment controls the composition ratio and dissolution rate of the mixed gas 31, it is safer than when the dissolved oxygen concentration in the culture solution 18 is controlled alone, as in Japanese Patent No. 2564008, which is shown as prior art. As shown in Figure 16, by controlling the dissolution rate, the utilization efficiency of the raw material gas 26 can be improved.

[0105] Furthermore, the advantages of combining composition ratio control and dissolution rate control of the mixed gas 31 in the culture apparatus 10 of the first embodiment are as follows. For example, if composition ratio control of the mixed gas 31 is performed alone without dissolution rate control, the amount of adjustment gas 33 required to maintain the hydrogen concentration and oxygen concentration at target values ​​outside the explosive range may be large. If the amount of adjustment gas 33 supplied increases, the amount of mixed gas 31 discharged also increases. Even if the mixed gas 31 is reused, there is a limit to the amount that can be reused, and any mixed gas 31 exceeding this limit must be released to the atmosphere. In this case, the adjustment gas 33 used to inactivate the mixed gas 31 is wasted.

[0106] Combining composition ratio control and dissolution rate control reduces the amount of hydrogen released into space 11A. Therefore, as shown in Fig. 16, in controlling the composition ratio of mixed gas 31, it is possible to reduce the supply amount of adjustment gas 33 required to maintain the hydrogen concentration or oxygen concentration at a target value outside the explosive range. In this way, by combining composition ratio control and dissolution rate control of mixed gas 31, it is possible to reduce waste of adjustment gas 33.

[0107] Furthermore, the culture apparatus 10 of the first embodiment does not simply reduce the amount of hydrogen supplied, but controls the amount of hydrogen supplied using an index known as the dissolution rate. Hydrogen that does not dissolve in the culture solution 18 is not consumed by the hydrogen-oxidizing bacteria 21 to be cultured and is instead released in vain. The culture apparatus 10 of the first embodiment can reduce the amount of hydrogen that is released in vain by using the dissolution rate as an index to reduce the amount of hydrogen supplied. This reduces concerns about a shortage of raw material for the hydrogen-oxidizing bacteria 21, and improves the utilization efficiency of hydrogen, which is the raw material gas 26.

[0108] Setting the target dissolution rate at 90% further improves safety. Furthermore, by controlling the hydrogen consumption rate, the utilization efficiency of the source gas 26 can be further improved.

[0109] In the above example, the dissolution rate was controlled by reducing the amount of hydrogen supplied. However, another method for improving the dissolution rate is to lower the temperature of the culture solution 18. The solubility of hydrogen can be changed by adjusting the temperature of the culture solution 18. Alternatively, the dissolution rate may be controlled by providing multiple types of bubble generators (sparger 28, for example) that generate bubbles with different diameters and selectively switching between them. This is because, as described above, the smaller the bubble diameter, the higher the dissolution rate.

[0110] Furthermore, in order to maintain the dissolution rate at or above the target value, it is effective to combine this with the bubble diameter setting shown in Figure 7. Similarly, as shown in Figure 8, it is also effective to take measures to reduce the surface tension by adding a surface tension reducing agent to the culture solution 18.

[0111] Furthermore, in the first embodiment, as an example, hydrogen-oxidizing bacteria 21 are used as the microorganism to be cultured, and the raw material gas 26 contains hydrogen as a combustible gas, and oxygen and carbon dioxide as other components. In the case of such a combination of the culture target and raw material gas 26, the technology of the present disclosure is particularly effective. This is because, first of all, the raw material gas 26 contains, as components, hydrogen, a combustible gas, as well as oxygen, a combustion-supporting gas. Therefore, safety measures to prevent explosions are extremely important, and the technology of the present disclosure, which can further improve safety, is particularly effective.

[0112] Furthermore, since the raw material gas 26 contains carbon dioxide, an inert gas, as a component thereof, by using carbon dioxide as the adjustment gas 33, it becomes possible to reuse the adjustment gas 33 as the raw material gas 26. Therefore, the technology of the present disclosure is effective in such a combination in terms of utilization efficiency as well.

[0113] Furthermore, in the culture apparatus 10 of the first embodiment, by combining the component separation mechanism 52 shown in Figures 2 and 3 and the gas separation mechanism 61 shown in Figures 2 and 4 as an example of a common configuration, it is effective in improving safety and improving the utilization efficiency of the raw material gas 26. First, in terms of safety, since flammable gases can be separated, it is easy to ensure the safety of the gas circulation path 39 and the gas reuse path 62. Furthermore, by separating specific components from the mixed gas 31, etc., it is easy to reuse them according to the purpose.

[0114] In addition, in the culture device 10 of the first embodiment, as an example of a common configuration shown in Figure 2, a technology is combined in which the mixed gas outlet 34 of the gas circulation path 39 is positioned so that the foam layer 18B can be taken in. Such a technology is effective in that it reduces adverse effects on sensors and enables accurate control.

[0115] Furthermore, the culture device 10 of the first embodiment is combined with a mechanism for reducing the concentration of the culture solution 18 removed from the culture tank 11, as shown in Fig. 4 as an example of a common configuration. Such a technique is effective in improving safety in the recovery path 56 and the recovery tank 57 downstream of the culture solution recovery mechanism 55.

[0116] In addition, the culture device 10 of the first embodiment is combined with an explosion suppression mechanism shown in Figures 2 and 4 as an example of a common configuration. Such a technology is effective in improving safety in the gas reuse path 62.

[0117] Furthermore, although the explosion suppression mechanism is exemplified by the gas separation mechanism 61 that separates hydrogen from the separated gas separated from the culture solution 18, other configurations are also possible. For example, when transferring the gas to be reused in the gas reuse path 62, a configuration is conceivable in which the composition ratio of the reused gas is controlled to a target value outside the explosive range by adding an inert gas such as the adjustment gas 33. Furthermore, an explosion suppression mechanism can be realized by configuring the gas reuse path 62 to eliminate ignition sources as much as possible. For example, a pump 22 having mechanical moving parts that generate frictional heat can be an ignition source. As shown in the fourth embodiment described below, an explosion suppression mechanism may be realized by replacing the pump 22 with a pressure-applying device that does not have moving parts (such as the fluid ejectors 75 and 76 shown in FIGS. 23 and 24).

[0118] In the culture device 10 of the first embodiment, it is not necessary to provide all of the elements shown as an example of the common configuration, and it is also possible to combine only some of them.

[0119] 3. Second Embodiment A culture device 10 according to a second embodiment will be described using Figures 17 to 21. In the second embodiment, the description of the example of the common configuration shown in Figures 1 to 9 and the configuration described in the first embodiment shown in Figures 10 to 16 will be omitted and the same reference numerals will be used.

[0120] The culture apparatus 10 of the second embodiment has a configuration in which the composition ratio control mechanism of the first embodiment is combined with a vertically long culture tank 111 as shown in Fig. 17. More specifically, in the culture tank 111 of the second embodiment, when the circle-equivalent diameter of a cross section perpendicular to the height direction of the culture tank 111 is DAm and the maximum height of the liquid surface 18A is H, the dimensions of the culture tank 111 satisfy the dimensional condition H / DAm ≥ 2. The height direction is the vertical direction.

[0121] Here, the "circle equivalent diameter" refers to the diameter of the circle when the cross section is circular, the diameter of the circumscribed circle when the cross section is polygonal, and the major axis when the cross section is elliptical or oval. The "maximum height of the liquid surface" refers to the height of the liquid surface 18A of the culture solution 18 when the maximum possible volume of the culture solution 18 is contained in the culture tank 111. The maximum possible volume is the maximum volume at which the culture process can be performed. The maximum height of the liquid surface 18A is the height measured when various sensors such as the water level gauge 66 are immersed in the culture solution 18 and when all elements that fluctuate the liquid surface 18A, such as the stirring rod 41 and the sparger 28, are stopped.

[0122] By using a vertically elongated culture tank 111 with such dimensional conditions, the dissolution rate of the flammable gas is improved. The raw material gas 26 supplied to the culture solution 18 rises toward the liquid surface 18A, and during the rise, a portion of the raw material gas 26 is dissolved in the culture solution 18. The undissolved raw material gas 26 is released into the space 11A above the liquid surface 18A and becomes a component of the mixed gas 31. Therefore, the longer the culture tank 111 is, the longer the dissolution time for the raw material gas 26 to dissolve can be secured, and therefore the amount of raw material gas 26 dissolved in the culture solution 18 increases, and the amount of raw material gas 26 contained in the mixed gas 31 is reduced accordingly. If the raw material gas 26 contains a flammable gas, the amount of flammable gas contained in the mixed gas 31 is reduced. This reduces the risk of explosion and improves safety.

[0123] In the second embodiment, the dissolution rate of the flammable gas is also improved by using a vertically long culture tank 111. As shown in Fig. 16, the improvement in the dissolution rate of the flammable gas also improves the utilization rate of the raw material gas 26. In addition, by combining this with composition ratio control, there is also the effect of reducing the supply amount of the adjustment gas 33. These effects are the same as those in the first embodiment.

[0124] The culture tank 111 has a cylindrical shape with a bottom. A cylindrical shape can more easily reduce bias in the concentration distribution of the culture solution 18 than a cylindrical shape with a polygonal cross section. In addition, a cylindrical shape is easier to manufacture than a polygonal cylindrical shape.

[0125] Furthermore, the dimensional condition is more preferably H / DAm≧13. This makes the culture tank 111 longer vertically, and further improves the dissolution rate of the flammable gas.

[0126] 7 in the example of the common configuration in the second embodiment, it is preferable that d90 is 1000 μm or less for the bubble diameter of the raw material gas 26. This is because, assuming that the dimensional condition of the culture tank 111 is H / DAm=2, by setting d90 to 1000 μm or less, bubbles will almost disappear near the liquid surface 18A.

[0127] Also in the second embodiment, it is effective to add a surface tension reducing agent to reduce the bubble diameter.

[0128] 17, the overall height dimension of the temperature regulator 47 in the culture tank 111 is preferably 30% or more of the maximum height of the liquid surface 18A. That is, when the height of the temperature regulator 47 is Ht, it is preferable to satisfy the condition Ht / H≧30%. Here, the meaning of "overall" includes the case where the continuous length Ht of one temperature regulator 47 is 30% or more, and, when multiple temperature regulators 47 are arranged in a divided manner, the total length of the divided parts is 30% or more.

[0129] When the culture tank 111 is vertically long, it is preferable that the temperature regulator 47 also has a length of 30% or more of the height H of the liquid surface 18A in terms of reducing temperature unevenness in the vertical direction.

[0130] Furthermore, the temperature regulator 47 may have various forms, and may be arranged so as to surround the outer periphery of the culture tank 111. For example, if the culture tank 111 is cylindrical, the temperature regulator 47 is also cylindrical. Alternatively, a plurality of temperature regulators 47 each having an arc-shaped cross section may be arranged around the outer periphery of the culture tank 111.

[0131] 18, the temperature regulator 47 may be disposed inside the culture tank 111. Of course, as shown in FIG. 18, the temperature regulator 47 may be disposed both inside and outside the culture tank 111.

[0132] As shown in FIG. 18 , it is preferable that at least a portion of the temperature regulator 47 is disposed inside the culture tank 111. This is because the temperature regulator 47 regulates the temperature of the culture solution 18 in the culture tank 111, and disposing the temperature regulator 47 inside the culture tank 111 is more energy efficient than disposing the temperature regulator 47 outside the culture tank 111. The shape of the temperature regulator 47 inside the culture tank 111 is, for example, cylindrical. Of course, multiple arc-shaped temperature regulators 47 may be disposed. Note that in FIG. 18 and FIG. 20 described below, the shape of the temperature regulator 47 disposed outside the culture tank 111 is simplified. In reality, the temperature regulator 47 disposed outside the culture tank 111 has, for example, an arc-shaped cross section in the horizontal direction perpendicular to the height direction, and is curved along the curved surface of the outer periphery of the culture tank 111.

[0133] As described above, the temperature regulator 47 is controlled by the processor 17, which adjusts the temperature of the culture solution 18 to a temperature suitable for culture via the temperature regulator 47. The temperature of the culture solution 18 may be kept constant during the culture period, or may be changed depending on the progress of the culture.

[0134] 19, there may be a plurality of temperature regulators 47, and each of the plurality of temperature regulators 47 may be arranged at a different position in the height direction of the culture tank 111. Because the culture tank 11 is vertically long, it is preferable from the viewpoint of reducing temperature unevenness in the height direction if the plurality of temperature regulators 47 are arranged at different heights. In FIG. 19, the symbols Ht1 and Ht2 indicate the respective height lengths of two temperature regulators 47 arranged side by side in the height direction.

[0135] 20 , a stirring rod 41 having a plurality of screws 41A may be provided, and the plurality of screws 41A may be arranged at different positions in the height direction of the culture tank 111. The screws 41A are an example of an "agitation unit" according to the technology of the present disclosure, and the stirring rod 41 is an example of an "agitation mechanism."

[0136] It is preferable to arrange the multiple screws 41A at different heights, since this reduces unevenness in the concentration of the substances dissolved or dispersed in the culture solution 18 along the height direction. The substances dissolved or dispersed in the culture solution 18 include culture targets (microorganisms or cells) such as hydrogen-oxidizing bacteria 21, and raw material gas 26.

[0137] 21 , in the case where there are multiple temperature regulators 47 and multiple screws 41A, multiple pairs each consisting of at least one temperature regulator 47 and at least one screw 41A may be arranged at different positions in the height direction of the culture tank 111. In this way, it is possible to reduce both temperature unevenness and concentration unevenness.

[0138] The dissolution rate control mechanism of the first embodiment may be combined with the culture apparatus 10 of the second embodiment. By combining the vertical culture tank 111 with the dissolution rate control mechanism, the amount of flammable gas contained in the mixed gas 31 can be further reduced. This reduces the risk of explosion of the mixed gas 31, further improving safety. Furthermore, by further improving the dissolution rate of the flammable gas, the consumption rate of the raw material gas 26, such as the hydrogen consumption rate of the hydrogen-oxidizing bacteria 21, also improves, thereby improving the utilization efficiency of the raw material gas 26.

[0139] When the dissolution rate is controlled, the target value of the dissolution rate is preferably 90% or more, as in the first embodiment, which ensures the effects of improving safety and the utilization efficiency of the source gas 26.

[0140] Furthermore, similarly to the first embodiment, the dissolution rate control may be combined with the consumption rate control of the flammable gas, which will more reliably improve the utilization efficiency of the source gas 26.

[0141] In the second embodiment, as an example, hydrogen-oxidizing bacteria 21 are used as the microorganisms to be cultured, and the raw material gas 26 contains hydrogen as a combustible gas, and oxygen and carbon dioxide as other components. In the case of such a combination of the culture target and raw material gas 26, the technology of the present disclosure is particularly effective. The reason is as explained in the first embodiment.

[0142] In the culture device 10 of the second embodiment, it is not necessary to provide all of the elements shown as examples of common configurations, and it is possible to combine only some of them. Furthermore, as shown by way of example in combination with dissolution rate control, the configurations of the second embodiment and the first embodiment may be appropriately combined.

[0143] 4. Third Embodiment A culture device 310 according to a third embodiment will be described using Figure 22. In the third embodiment, the description of the above-described configurations, such as the example of the common configuration shown in Figures 1 to 9 and the first embodiment shown in Figures 10 to 16, will be omitted and the same reference numerals will be used.

[0144] As shown in FIG. 22 , the culture apparatus 310 of the third embodiment has a bubble generator 128 for mixing a raw material gas 26 with the culture solution 18 before it is supplied to the culture tank 11, and is provided with a culture solution supply path 70 that is disposed between the culture solution tank 13 and the culture tank 11 and supplies the culture solution 18 mixed with the raw material gas 26 by the bubble generator 128 to the culture tank 11, and is provided with a culture solution supply path 70 that is provided separately from the supply path 15A that supplies hydrogen-oxidizing bacteria 21 to the culture tank 11.

[0145] In one example of the culture device 310, a bubble generator 128 is provided in the culture solution tank 13. A supply path 12A for the raw material gas 26 is connected to the bubble generator 128 in the culture solution tank 13. The culture solution 18 mixed with the raw material gas 26 in the culture solution tank 13 is supplied to the culture tank 11 through a culture solution supply path 70. The culture tank 11 is not provided with a bubble generator such as a sparger 28. The culture tank 11 is supplied with hydrogen-oxidizing bacteria 21 through a supply path 15A, which serves as a culture target supply path.

[0146] When bubbles of the raw material gas 26 generated by the bubble generator 128 come into contact with the culture target (microorganisms or cells) such as the hydrogen-oxidizing bacteria 21, the culture target is damaged. If the culture target is damaged by the bubbles, the culture target may die, and the amount of the culture target in the culture solution 18 may decrease. If the number of the culture target in the culture solution 18 decreases, the consumption rate of the flammable gas contained in the raw material gas 26, such as the hydrogen consumption rate, also decreases. If the consumption rate of the flammable gas decreases, the amount of the flammable gas contained in the mixed gas 31 increases. This increases the risk of explosion and reduces safety.

[0147] The culture apparatus 310 of the third embodiment is provided with a culture solution supply path 70 for supplying a culture solution 18 pre-mixed with a raw material gas 26, separate from the supply path 15A for the hydrogen-oxidizing bacteria 21. This reduces the chance of bubbles of the raw material gas 26 coming into contact with the hydrogen-oxidizing bacteria 21 in the culture tank 11. This reduces damage to the hydrogen-oxidizing bacteria 21 from the bubbles and suppresses a decrease in the number of hydrogen-oxidizing bacteria 21 in the culture solution 18. Suppressing a decrease in the number of hydrogen-oxidizing bacteria 21 improves the consumption rate of flammable gases, such as the hydrogen consumption rate, and reduces the amount of flammable gas contained in the mixed gas 31. This reduces the risk of explosion and improves safety.

[0148] Furthermore, when damage to the hydrogen-oxidizing bacteria 21 is reduced, the hydrogen consumption rate increases, and the utilization efficiency of the raw material gas 26 and the culture efficiency also improve.

[0149] 22, in the culture device 310 of the third embodiment, a temperature regulator 47 is provided in the culture solution tank 13 in addition to the culture tank 11. This allows the temperature of the culture solution 18 in the culture tank 11 and the temperature in the culture solution tank 13 to be adjusted to the same temperature.

[0150] In the culture device 310, the culture solution 18 to which the hydrogen-oxidizing bacteria 21 are supplied is located in the culture tank 11, and the culture solution 18 to which the raw material gas 26 is supplied is located in the culture solution tank 13. The culture solutions 18 in the culture solution tank 13 and the culture tank 11 are mixed through the culture solution supply line 70. If there is a temperature difference between the two, the temperature difference may cause uneven concentrations of the raw material gas 26 in the culture solution 18 after mixing. Uneven concentrations of the raw material gas 26 may result in the death of the hydrogen-oxidizing bacteria 21 in areas with low concentrations of the raw material gas 26. By providing a temperature regulator 47 in each of the culture tank 11 and the culture solution tank 13, damage to the culture target, such as the hydrogen-oxidizing bacteria 21, caused by temperature differences in the culture solution 18 can be reduced. This improves the hydrogen consumption rate by the hydrogen-oxidizing bacteria 21 and reduces the amount of hydrogen contained in the mixed gas 31, thereby further improving safety. Similarly, the utilization efficiency of the raw material gas 26 and the culture efficiency are also improved.

[0151] Furthermore, since the raw material gas 26 and the culture solution 18 only need to be mixed before being supplied to the culture tank 11, it is also possible to provide a bubble generator 128, for example, in the culture solution supply path 70. However, as shown in Figure 22, providing the bubble generator 128 in the culture solution tank 13 allows for more space than providing it in the culture solution supply path 70, making it easier to install the bubble generator 128.

[0152] The bubble generator 128 may be a sparger 28, a swirling shear type that generates bubbles by swirling shear force, or the above-mentioned ejector or static mixer type. These types of bubble generators have higher output and can supply more raw material gas 26 than the sparger 28, making them suitable for mass production. This improves the culture efficiency. However, the higher the output of the bubble generator 128, the greater the damage to the hydrogen-oxidizing bacteria 21 caused by bubbles. In the third embodiment, the raw material gas 26 and the culture solution 18 can be mixed without considering contact between the bubbles of the raw material gas 26 and the hydrogen-oxidizing bacteria 21. Therefore, a high-output bubble generator 128, such as a swirling shear type, can be used.

[0153] Similarly to the first embodiment, the culture apparatus 310 of the third embodiment also includes a culture solution circulation path 354 that removes a portion of the culture solution 18 from the culture tank 11, recovers a portion of the culture target, such as the hydrogen-oxidizing bacteria 21, from the removed culture solution 18, and returns the remaining culture solution 18 to the culture tank 11. The culture solution circulation path 354 of the third embodiment includes a culture solution supply path 70 that connects the culture solution tank 13 and the culture tank 11. The culture solution circulation path 354 of the third embodiment differs from the culture solution circulation path 54 of the first embodiment in that the culture solution is returned to the culture tank 11 via the culture solution tank 13. This culture solution circulation path 354 enables perfusion culture, in which the culture solution 18 is perfused. Even when perfusion culture is performed, the culture solution 18 is returned to the culture solution tank 13 after the hydrogen-oxidizing bacteria 21 have been recovered, reducing contact between bubbles of the raw material gas 26 and the hydrogen-oxidizing bacteria 21. This reduces damage to the hydrogen-oxidizing bacteria 21 from bubbles.

[0154] In the third embodiment, as an example, hydrogen-oxidizing bacteria 21 are used as the microorganism to be cultured, and the raw material gas 26 contains hydrogen as a combustible gas and oxygen and carbon dioxide as other components. In the case of such a combination of the culture target and raw material gas 26, the technology of the present disclosure, which aims to improve safety, is particularly effective, as in the first embodiment.

[0155] Furthermore, the hydrogen-oxidizing bacteria 21 consume hydrogen and carbon dioxide as an energy source and a carbon source, respectively. As described above, in the culture apparatus 310 of the third embodiment, the raw material gas 26 and the culture solution 18 are mixed in the culture solution tank 13, so there is no need to consider contact between the hydrogen-oxidizing bacteria 21 and bubbles of the raw material gas 26, and a high-output bubble generator 128 can be used. Therefore, compared to the sparger 28 (see FIG. 2 ), it is possible to sufficiently supply the raw material gas 26 to the culture solution 18 and dissolve it. Therefore, the culture apparatus 310 of the third embodiment can provide sufficient nutrients to the hydrogen-oxidizing bacteria 21, which is advantageous in terms of culture efficiency.

[0156] 3, as an example of a common configuration, the source gas 26 may be supplied with each component of hydrogen, oxygen, and carbon dioxide separately. This makes it difficult for concentration distribution of each component to occur in the culture solution 18, makes it difficult for a shortage of source gas 26 for the hydrogen-oxidizing bacteria 21, and reduces damage to the hydrogen-oxidizing bacteria 21.

[0157] 7 as an example of a common configuration, the bubble diameter d90 of the source gas 26 may be 1000 μm or less. As described above, by reducing the bubble diameter, the dissolution rate can be further improved. This improves safety and utilization efficiency of the source gas 26.

[0158] Furthermore, in the third embodiment, the composition ratio control shown in the first embodiment may be performed, which further improves safety.

[0159] In the culture device 310 of the third embodiment, it is not necessary to provide all of the elements shown as examples of common components, and only some of them may be combined. Furthermore, the third embodiment may be appropriately combined with the components of the first and second embodiments, such as a combination of dissolution rate control and a vertically long culture tank 111.

[0160] 5. Fourth Embodiment A culture device 410 according to a fourth embodiment will be described using Figures 23 and 24. In the fourth embodiment, the description of the above-described configurations, such as the example of the common configuration shown in Figures 1 to 9 and the first embodiment shown in Figures 10 to 16, will be omitted and the same reference numerals will be used.

[0161] As shown in FIG. 23 , the culture apparatus 410 of the fourth embodiment includes a gas circulation path 439 for reusing the mixed gas 31 in the space 11A as the raw material gas 26, and a fluid ejector 75 disposed on the gas circulation path 439 and applying a circulation pressure to the mixed gas 31 to circulate the mixed gas 31. The fluid ejector 75 is an example of a pressure applying device that does not have any mechanical moving parts and applies a circulation pressure to the mixed gas 31 using a driving fluid input from an external source. Although the pump 22 is a pressure applying device, it has mechanical moving parts such as a rotor, and the mechanical moving parts come into contact with the mixed gas 31 to which the circulation pressure is applied. The pump 22 is distinguished from the pressure applying device of the present application, which does not have any mechanical moving parts, in that it has a mechanical moving part.

[0162] The fluid ejector 75 includes a first input port 75A into which the mixed gas 31 is input, a second input port 75B into which the driving fluid is input, and an output port 75C from which the mixed gas 31 is output. A nozzle 75D for ejecting the driving fluid is provided at the back of the second input port 75B.

[0163] The nozzle 75D is tapered toward the tip where the nozzle outlet is formed. The tip of the nozzle 75D is located at the point where the flow path from the first input port 75A and the flow path from the second input port 75B converge. When the driving fluid is input from the outside to the second input port 75B, the tapered shape of the nozzle 75D increases the flow velocity of the driving fluid as it passes through the nozzle 75D and the driving fluid is ejected in this state. Because the flow velocity of the driving fluid is high and the pressure is low, the mixed gas 31 input from the first input port 75A is sucked into the driving fluid and output from the output port 75C together with the driving fluid. This imparts a circulating pressure to the mixed gas 31.

[0164] An example of the driving fluid is the culture solution 18 extracted from the culture tank 11. The culture solution 18 as the driving fluid is pressurized by the pump 22 and input into the fluid ejector 75. A mixture of the culture solution 18 and the mixed gas 31 is output from the output port 75C of the fluid ejector 75. A culture solution circulation path 454 is connected to the output port 75C. The culture solution 18 and the mixed gas 31 are returned to the culture tank 11 through the culture solution circulation path 454. This causes the mixed gas 31 to circulate. In this example, the culture solution circulation path 454 is also used as the gas circulation path 439.

[0165] As described above, the culture apparatus 410 of the fourth embodiment circulates the mixed gas 31 by providing a fluid ejector 75 in the gas circulation path 439 through which the mixed gas 31 circulates. The fluid ejector 75 is an example of a pressure-applying device that does not have any mechanical moving parts. Because it does not have any mechanical moving parts, heat generation due to friction is not generated and ignition sources such as high temperatures, sparks, and static electricity are not generated. Ignition sources are one of the three elements of explosion. Therefore, in the culture apparatus 410, even when the mixed gas 31 is reused as the raw material gas 26, the risk of explosion is low, and safety is improved compared to conventional methods.

[0166] The culture device 410 also has a pump 22 with a mechanically movable part to apply pressure to the culture solution 18 as a driving fluid. However, the pump 22 is not disposed in the gas circulation path 439 through which the mixed gas 31 circulates, and therefore the mixed gas 31 and the pump 22 do not come into contact with each other, and the pump 22 does not become an ignition source that could cause an explosion of the mixed gas 31.

[0167] In this way, in the culture apparatus 410 of the fourth embodiment, devices that could be ignition sources, such as the pump 22, are excluded from the gas circulation path 439 that circulates the mixed gas 31. Therefore, even if the composition ratio of the mixed gas 31 is within the explosive range, safety is higher than when the pump 22 is provided in the gas circulation path 439.

[0168] In the culture device 410, the culture solution 18 is used as the driving fluid. The culture solution 18 can be reused in the culture process by circulating it, just like the mixed gas 31. Therefore, using the culture solution 18 as the driving fluid results in less waste than using a dedicated fluid that cannot be used in the culture process as the driving fluid. Furthermore, since the mixed gas 31 is dissolved in the culture solution 18 and reused, using the culture solution 18 as the driving fluid is also advantageous in terms of preventing impurities from being mixed into the raw material gas 26.

[0169] As described above, the culture apparatus 410 of the fourth embodiment is relatively safe even when the composition ratio of the mixed gas 31 is within the explosive range. Therefore, the supply amount of the raw material gas 26 can be determined based on criteria that prioritize the culture efficiency of the hydrogen-oxidizing bacteria 21 rather than safety.

[0170] For example, in the culture device 410, the consumption amount of the raw material gas 26 consumed by the hydrogen-oxidizing bacteria 21 out of the raw material gas 26 supplied to the culture tank 11 during culture may be measured, and control may be performed such that the raw material gas 26 is supplied in an amount equal to or greater than the consumption amount of the raw material gas 26. The culture device 410 is highly safe, and therefore such control is easy to perform. The consumption amount of the raw material gas 26 can be measured using a procedure similar to that described in FIG. 12 in the first embodiment. The raw material gas supply unit including the processor 17 calculates the amount of raw material gas 26 equal to or greater than the consumption amount of the measured raw material gas 26, and determines the supply amount. Such control allows for an abundant supply of the raw material gas 26.

[0171] Specifically, the supply amount of the raw material gas 26 supplied to the culture tank 11 through the raw material gas supply unit and the gas circulation path 39 may be 2 to 15 times the consumption amount of the raw material gas 26. In other words, the total supply amount of the raw material gas 26 supplied to the culture tank 11 is controlled to be 2 to 15 times the consumption amount of the raw material gas 26 in the culture tank 11. If the total supply amount of the raw material gas 26 is set to this level, a sufficient amount of the raw material gas 26 required by the hydrogen-oxidizing bacteria 21 can be provided, and there will be no shortage of the raw material gas 26. Furthermore, if such a sufficient amount of the raw material gas 26 is provided, unevenness in the concentration of the raw material gas 26 in the culture tank 11 will also be reduced. This can improve the culture efficiency.

[0172] Of course, the culture apparatus 410 of the fourth embodiment can be appropriately combined with the configurations of the above-described embodiments. For example, composition ratio control may be performed to maintain the composition ratio of the mixed gas 31 shown in Fig. 11 at a target value within the explosive range. In the fourth embodiment, since ignition sources are removed from the gas circulation path 439, safety is high even if the composition ratio of the mixed gas 31 is within the explosive range. However, by controlling the composition ratio of the mixed gas 31, safety is further improved.

[0173] 23, a configuration may be adopted in which the mixed gas outlet 34 of the gas circulation path 439 is disposed at a position where the foam layer 18B can be taken in. This can reduce the adverse effects of the foam layer 18B, as shown in the example of the common configuration.

[0174] Furthermore, in the fourth embodiment, as an example, hydrogen-oxidizing bacteria 21 are used as the microorganism to be cultured, and the raw material gas 26 contains hydrogen as a combustible gas, and oxygen and carbon dioxide as other components. In the case of such a combination of the culture target and raw material gas 26, the technology of the present disclosure is particularly effective. As described above, the raw material gas 26 contains hydrogen, which is a combustible gas, as well as oxygen, which is a combustion-supporting gas. Therefore, safety measures to prevent explosions are extremely important, and the technology of the present disclosure, which can further improve safety, is particularly effective.

[0175] In this example, the output port 75C of the fluid ejector 75 is connected to the culture tank 11 via the piping of the culture solution circulation path 454, but the output port 75C may also be connected directly to the culture tank 11 without the piping.

[0176] In this example, a fluid ejector 75 is used as a pressure applying device that does not have any mechanical moving parts. Many existing fluid ejector 75 products are easily usable. Of course, instead of the fluid ejector 75, a swirling shear type pressure applying device, for example, can be used as a pressure applying device that does not have any mechanical moving parts. A swirling shear type pressure applying device swirls the driving fluid to generate a high-speed swirling flow, and applies a circulating pressure to the mixed gas 31 by the pressure of the high-speed swirling flow. Furthermore, as an example of a pressure applying device, the bubble generating device "YJ Nozzle" manufactured by EnviroVision Co., Ltd. can also be used. The "YJ Nozzle" can be used as a bubble generating device, but like the fluid ejector 75 shown in FIG. 23 , it can also be used as a pressure applying device that applies pressure to a fluid by utilizing pressure changes in a flow path.

[0177] In the example of Figure 23, the culture solution 18 and the mixed gas 31 are returned to the culture tank 11 in a mixed state. However, as shown in Figure 24, the culture solution 18 and the mixed gas 31 may be separated and returned to the culture tank 11.

[0178] In this case, the culture solution 18 and the mixed gas 31 are output in a mixed state from the output port 75C of the fluid ejector 75, and then the culture solution 18 and the mixed gas 31 are separated by the gas separation mechanism 61. The separated culture solution 18 is then returned to the culture tank 11 through the culture solution circulation path 454. Meanwhile, the separated separated gas is returned to the culture tank 11 through the gas reuse path 62. For example, a fluid ejector 76 that applies a circulation pressure to the separated gas is disposed in the gas reuse path 62. As an example, the fluid ejector 76 uses carbon dioxide as a driving fluid. Because carbon dioxide is a component of the separated gas, impurities are not mixed into the separated gas. The separated gas is returned to the culture tank 11 through the fluid ejector 76.

[0179] In each of the above embodiments, hydrogen-oxidizing bacteria 21 have been described as an example of the microorganisms, but the technology of the present disclosure can also be applied to microorganisms or cells other than the hydrogen-oxidizing bacteria 21. Examples of the microorganisms include acetogenic bacteria such as Clostridium autoethanogenum and methane-utilizing bacteria such as Methylococcus caprasulatus. In the case of acetogenic bacteria, the components of the raw material gas 26 include hydrogen (H ２ ), carbon monoxide (CO) and carbon dioxide (CO ２ In the case of methanotrophs, the raw material gas 26 contains methane (CH ４ ) and air. A cell is a morphological and / or functional unit that constitutes an organism, and the organism from which the cell originates is not particularly limited, but may be an animal or a plant. The cell may be an established cell line or a genetically modified cell, and may include artificial cells. Examples of such cells include CHO cells (Chinese hamster ovary cells), HEK293 cells (Human Embryonic Kidney cells 293), and Sf9 cells (Spodoptera afrugiperda cells 9).

[0180] (Regarding Supplementary Clauses) Furthermore, from the explanation of the first to fourth embodiments above, the inventions described in the following first to fourth supplementary clauses can be understood.

[0181] (First Supplementary Item) [First Supplementary Item 1] A culture apparatus for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances, comprising: a culture tank that contains a culture solution for culturing the microorganisms or cells; a raw material gas supply unit that supplies the raw material gas to the culture tank; a composition ratio control mechanism that measures the composition ratio of the mixed gas in a space present above the liquid surface of the culture solution in the culture tank and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosive range; a gas circulation path for reusing the mixed gas in the space as a raw material gas; and a dissolution rate control mechanism that measures a flammable gas solubility rate, which is the rate of flammable gas dissolved in the culture solution out of the flammable gas contained in the raw material gas supplied to the culture tank through the gas circulation path or the raw material gas supply unit, during culture, and maintains the measured flammable gas solubility rate at or above a predetermined target value. [Supplementary Item 1 2] The culture apparatus according to Supplementary Item 1, wherein the target value of the flammable gas dissolution rate is 90% or more. [Supplementary Item 1 3] The culture apparatus according to Supplementary Item 1 or 2, wherein the dissolution rate control mechanism further measures a flammable gas consumption rate, which is the proportion of flammable gas consumed by microorganisms or cells among the flammable gases contained in the raw material gas supplied to the culture tank through the gas circulation path and the raw material gas supply unit, during culture, and maintains the measured flammable gas consumption rate at 90% or more by controlling the flammable gas dissolution rate. [Supplementary Item 1 4] The culture apparatus according to any one of Supplementary Item 1 to Supplementary Item 3, wherein the diameter d90 of bubbles of the raw material gas generated in the culture solution is 1000 μm or less. [Supplementary Item 1 5] The culture apparatus according to any one of Supplementary Item 1 to Supplementary Item 4, wherein the diameter d90 of bubbles of the raw material gas generated in the culture solution is 1000 μm or less. [First Supplementary Item 6] The culture device according to any one of First Supplementary Item 1 to First Supplementary Item 5, wherein the surface tension of the culture solution is 65 mN / m or less. [First Supplementary Item 7] The culture device according to any one of First Supplementary Item 1 to First Supplementary Item 6, wherein the microorganisms are hydrogen-oxidizing bacteria, the raw material gas contains hydrogen as a combustible gas and oxygen and carbon dioxide as other components, and the adjustment gas is carbon dioxide.[First Supplementary Item 8] The culture device according to any one of First Supplementary Item 1 to First Supplementary Item 7, comprising a first component separation mechanism that separates a specific component from the mixed gas extracted from the culture tank, or a second component separation mechanism that separates a specific component from the separated gas separated from the culture liquid extracted from the culture tank. [First Supplementary Item 9] The culture device according to any one of First Supplementary Item 1 to First Supplementary Item 8, wherein in the gas circulation path, a mixed gas extraction port that extracts the mixed gas from the culture tank is positioned at a position that allows extraction of a foam layer present on the liquid surface in the culture tank. [First Supplementary Item 10] The culture device according to any one of First Supplementary Item 1 to First Supplementary Item 9, comprising: a culture medium recovery mechanism that recovers a recovery medium that is a portion of the culture medium containing produced organic substances from the culture medium removed from the culture tank, a recovery medium tank that stores the recovery medium containing the organic substances, and a concentration reduction mechanism that reduces the concentration of dissolved flammable gas contained in the recovery medium stored in the recovery medium tank to 1 / 10 or less of the concentration of dissolved flammable gas contained in the culture medium in the culture tank. [First Supplementary Item 11] The culture device according to any one of First Supplementary Item 1 to First Supplementary Item 10, comprising an explosion suppression mechanism that suppresses explosions in a gas recycling path for recycling gas separated from the culture medium. [First Supplementary Item 12] A control method for a culture apparatus for culturing microorganisms or cells, comprising a culture tank containing a culture solution for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of an organic substance, and a raw material gas supply unit that supplies the raw material gas containing a flammable gas to the culture tank, the control method comprising: measuring a composition ratio of a mixed gas in a space present above the liquid surface of the culture solution in the culture tank, and supplying an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosive range; and measuring, during the culture, a flammable gas solubility rate, which is the rate of flammable gas dissolved in the culture solution out of the flammable gas contained in the raw material gas supplied to the culture tank through a gas circulation path or the raw material gas supply unit for reusing the mixed gas in the space as a raw material gas, and maintaining the measured flammable gas solubility rate at a predetermined target value.

[0182] (Second Supplementary Item) [Second Supplementary Item 1] A culture apparatus for culturing microorganisms or cells that utilize a feed gas containing a flammable gas for growth or production of organic substances, comprising: a culture tank containing a culture solution for culturing the microorganisms or cells; a feed gas supply unit that supplies the feed gas to the culture tank; and a composition ratio control mechanism that measures the composition ratio of the mixed gas in a space above the liquid surface of the culture solution in the culture tank and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosion range, wherein the dimensions of the culture tank satisfy the condition H / DAm≧2, where DAm is the circle-equivalent diameter of a cross section perpendicular to the height direction of the culture tank and H is the maximum height of the liquid surface. [Second Supplementary Item 2] The culture apparatus according to Second Supplementary Item 1, wherein the culture tank is cylindrical with a bottom. [Second Supplementary Item 3] The culture device according to Second Supplementary Item 1 or Second Supplementary Item 2, wherein the condition is H / DAm≧13. [Second Supplementary Item 4] The culture device according to any one of Second Supplementary Item 1 to Second Supplementary Item 3, wherein the bubble diameter d90 of the raw material gas generated in the culture solution is 1000 μm or less. [Second Supplementary Item 5] The culture device according to any one of Second Supplementary Item 1 to Second Supplementary Item 4, wherein the culture device has a temperature regulator that regulates the temperature of the culture solution, and at least a part of the temperature regulator is disposed in the culture tank. [Second Supplementary Item 6] The culture device according to Second Supplementary Item 5, wherein the dimension of the temperature regulator in the height direction of the culture tank is 30% or more of the maximum height of the liquid surface as a whole. [Second Supplementary Item 7] The culture device according to Second Supplementary Item 5 or Second Supplementary Item 6, wherein the temperature regulator is disposed at a different position in the height direction of the culture tank. [Second Supplementary Item 8] The culture device according to any one of Second Supplementary Item 5 to Second Supplementary Item 7, which includes an agitation mechanism having a plurality of agitation units that agitate the culture solution, and the plurality of agitation units are arranged at different positions in the height direction of the culture tank. [Second Supplementary Item 9] The culture device according to Second Supplementary Item 8, in the case where the culture device has a plurality of temperature regulators and a plurality of agitation units, wherein a plurality of pairs, each of which combines at least one temperature regulator and at least one agitation unit, are arranged at different positions in the height direction of the culture tank.[Second Supplementary Item 10] The culture apparatus according to any one of Second Supplementary Item 1 to Second Supplementary Item 9, comprising: a gas circulation path for reusing the mixed gas in the space as a raw material gas; and a dissolution rate control mechanism for measuring a combustible gas solubility rate, which is the proportion of combustible gas dissolved in the culture solution among combustible gases contained in the raw material gas supplied to the culture tank through the gas circulation path and the raw material gas supply unit, during culture, and maintaining the measured combustible gas solubility rate at a preset target value. [Second Supplementary Item 11] The culture apparatus according to Second Supplementary Item 10, wherein the target value of the combustible gas solubility rate is 90% or more. [Second Supplementary Item 12] The culture device according to Second Supplementary Item 10 or Second Supplementary Item 11, wherein the dissolution rate control mechanism further measures a combustible gas consumption rate of combustible gas consumed by the microorganisms or cells among combustible gases contained in the raw material gas supplied to the culture tank through the gas circulation path or the raw material gas supply unit during culture, and maintains the measured combustible gas consumption rate at 90% or more by controlling the dissolution rate of the combustible gas. [Second Supplementary Item 13] The culture device according to any one of Second Supplementary Item 1 to Second Supplementary Item 12, wherein the microorganisms are hydrogen-oxidizing bacteria, the raw material gas contains hydrogen as a combustible gas and contains oxygen and carbon dioxide as other components, and the adjustment gas is carbon dioxide. [Second Supplementary Item 14] The culture apparatus according to any one of Second Supplementary Items 1 to 13, comprising a first component separation mechanism that separates a specific component from the mixed gas extracted from the culture tank, or a second component separation mechanism that separates a specific component from the separated gas separated from the culture solution extracted from the culture tank. [Second Supplementary Item 15] The culture apparatus according to any one of Second Supplementary Items 11 to 14, comprising: a gas circulation path for reusing the mixed gas in the space as a raw material gas; and a dissolution rate control mechanism that measures a combustible gas solubility rate, which is the rate of combustible gas dissolved in the culture solution among combustible gases contained in the raw material gas supplied to the culture tank through the gas circulation path and the raw material gas supply unit, during culture, and maintains the measured combustible gas solubility rate at a predetermined target value, and in the gas circulation path, a mixed gas outlet for extracting the mixed gas from the culture tank is positioned at a position where a foam layer present on the liquid surface in the culture tank can be taken in.[Second Supplementary Item 16] The culture device according to any one of Second Supplementary Items 1 to 15, comprising: a culture medium recovery mechanism that recovers a recovery medium that is a portion of the culture medium containing produced organic substances from the culture medium removed from the culture tank, a recovery medium tank that stores the recovery medium containing the organic substances, and a concentration reduction mechanism that reduces the concentration of dissolved flammable gas contained in the recovery medium stored in the recovery medium tank to 1 / 10 or less of the concentration of dissolved flammable gas contained in the culture medium in the culture tank. [Second Supplementary Item 17] The culture device according to any one of Second Supplementary Item 1 to 16, comprising an explosion suppression mechanism that suppresses explosions in a gas recycling path for recycling gas separated from the culture medium. [Second Supplementary Item 18] A control method for a culture apparatus for culturing microorganisms or cells, comprising a culture tank containing a culture solution for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances, and a raw material gas supply unit that supplies the raw material gas containing a flammable gas to the culture tank, wherein the dimensions of the culture tank satisfy the condition H / DAm≧2, where DAm is the equivalent circle diameter of a cross section perpendicular to the height direction of the culture tank, and H is the maximum height of the liquid surface; and the method measures the composition ratio of the mixed gas in a space above the liquid surface of the culture solution in the culture tank, and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosive range.

[0183] (Supplementary Item 3) [Supplementary Item 3 1] A culture apparatus for culturing microorganisms or cells that utilize a feed gas containing a flammable gas for growth or production of an organic substance, comprising: a culture vessel containing a culture medium for culturing the microorganisms or cells, a culture medium tank for storing the culture medium to be supplied to the culture vessel, a culture subject supply path for supplying the microorganisms or cells to the culture vessel, a feed gas tank for storing the feed gas, a bubble generator for mixing the feed gas with the culture medium before being supplied to the culture vessel, and a culture medium supply path disposed between the culture medium tank and the culture vessel, for supplying the culture medium mixed with the feed gas by the bubble generator to the culture vessel, the culture medium supply path being separate from the culture subject supply path. [Supplementary Item 3 2] The culture apparatus according to Supplementary Item 3 1, wherein the culture vessel and the culture medium tank are each provided with a temperature regulator for adjusting the temperature of the culture medium. [Supplementary Item 3] The culture device according to Supplementary Item 3 or 2, wherein the bubble generator is provided in the culture solution tank. [Supplementary Item 34] The culture device according to any one of Supplementary Item 3 to 3, wherein the bubble generator generates bubbles by rotational shear force. [Supplementary Item 35] The culture device according to any one of Supplementary Item 3 to 4, wherein the culture device is provided with a culture solution circulation path that removes a portion of the culture solution from the culture tank, recovers a portion of the microorganisms or cells from the removed culture solution, and returns the remaining culture solution after recovery to the culture tank via the culture solution tank. [Supplementary Item 36] The culture device according to any one of Supplementary Item 3 to 5, wherein the microorganisms are hydrogen-oxidizing bacteria, and the feedstock gas contains hydrogen as a combustible gas and oxygen and carbon dioxide as other components. [Supplementary Item 3 7] The culture device according to Supplementary Item 3 6, wherein the raw material gas is supplied with each component of hydrogen, oxygen, and carbon dioxide separately. [Supplementary Item 3 8] The culture device according to any one of Supplementary Item 3 1 to Supplementary Item 3 7, wherein the diameter of bubbles of the raw material gas generated in the culture solution is d90 of 1000 μm or less.[Supplementary Item 3 9] The culture device according to any one of Supplementary Items 3 to 8, comprising a composition ratio control mechanism that measures the composition ratio of the mixed gas in a space present above the surface of the culture solution in the culture tank and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a preset target value outside the explosion range. [Supplementary Item 3 10] The culture device according to any one of Supplementary Items 3 to 9, comprising a first component separation mechanism that separates a specific component from the mixed gas extracted from the culture tank, or a second component separation mechanism that separates a specific component from a separated gas separated from the culture solution extracted from the culture tank. [Supplementary Item 3 11] The culture device according to any one of Supplementary Items 3 to 10, wherein in a gas circulation path that circulates the mixed gas extracted from the culture tank, a mixed gas extraction port that extracts the mixed gas from the culture tank is positioned at a position that allows extraction of a foam layer present on the liquid surface of the culture solution in the culture tank. [Supplementary Item 3 12] The culture device according to any one of Supplementary Items 3 to 11, comprising: a culture solution recovery mechanism that recovers a recovery solution that is a portion of the culture solution containing produced organic substances from the culture solution extracted from the culture tank; a recovery solution tank that stores the recovery solution containing the organic substances; and a concentration reduction mechanism that reduces the dissolved combustible gas concentration in the recovery solution stored in the recovery solution tank to 1 / 10 or less of the dissolved combustible gas concentration in the culture solution in the culture tank. [3rd Supplementary Item 13] The culture device according to any one of 3rd Supplementary Item 1 to 3rd Supplementary Item 12, which is provided with an explosion suppression mechanism that suppresses explosion in a gas recycling path for recycling gas separated from the culture solution.

[0184] (Fourth Supplementary Item) [Fourth Supplementary Item 1] A culture apparatus for culturing microorganisms or cells that utilize a feed gas containing a flammable gas for growth or production of organic substances, comprising: a culture vessel containing a culture solution for culturing the microorganisms or cells; a feed gas supply unit that supplies the feed gas to the culture vessel; a gas circulation path for reusing a mixed gas in a space above the surface of the culture solution in the culture vessel as the feed gas; and a pressure applying device that is disposed on the gas circulation path and applies a circulation pressure to the mixed gas to circulate the mixed gas, wherein the pressure applying device has no mechanically moving parts and applies the circulation pressure to the mixed gas by an input driving fluid. [Fourth Supplementary Item 2] The culture apparatus according to Fourth Supplementary Item 1, wherein the pressure applying device is a fluid ejector. [Fourth Supplementary Item 3] The culture apparatus according to Fourth Supplementary Item 2, wherein the driving fluid input to the fluid ejector is the culture solution removed from the culture vessel. [Fourth Supplementary Item 4] The culture device according to any one of Fourth Supplementary Item 1 to Fourth Supplementary Item 3, wherein the amount of raw material gas consumed by the microorganisms or cells out of the raw material gas supplied to the culture tank during culture is measured, and the raw material gas supply unit supplies raw material gas at an amount equal to or greater than the amount of raw material gas consumed. [Fourth Supplementary Item 5] The culture device according to any one of Fourth Supplementary Item 1 to Fourth Supplementary Item 4, wherein the amount of raw material gas supplied to the culture tank through the raw material gas supply unit and the gas circulation path is 2 to 15 times the amount of raw material gas consumed. [Fourth Supplementary Item 6] The culture device according to any one of Fourth Supplementary Item 1 to Fourth Supplementary Item 5, comprising a composition ratio control mechanism that measures the composition ratio of the mixed gas in a space above the liquid surface of the culture solution in the culture tank, and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a predetermined target value outside the explosive range. [4th Supplementary Item 7] The culture apparatus according to any one of 4th Supplementary Item 1 to 4th Supplementary Item 6, wherein in the gas circulation path, a mixed gas outlet for extracting the mixed gas from the culture tank is arranged at a position where the foam layer present on the liquid surface in the culture tank can be extracted.[4th Supplementary Item 8] The culture device according to any one of 4th Supplementary Items 1 to 7, wherein the microorganism is a hydrogen-oxidizing bacterium, and the raw material gas contains hydrogen as a combustible gas and oxygen and carbon dioxide as other components. [4th Supplementary Item 9] The culture device according to any one of 4th Supplementary Items 1 to 8, comprising a first component separation mechanism that separates a specific component from the mixed gas extracted from the culture tank, or a second component separation mechanism that separates a specific component from the separated gas separated from the culture solution extracted from the culture tank. [Fourth Supplementary Item 10] The culture device according to any one of Fourth Supplementary Item 1 to Fourth Supplementary Item 9, comprising: a culture medium recovery mechanism that recovers a recovery medium that is a portion of the culture medium containing produced organic substances from the culture medium removed from the culture tank, a recovery medium tank that stores the recovery medium containing the organic substances, and a concentration reduction mechanism that reduces the concentration of dissolved flammable gas contained in the recovery medium stored in the recovery medium tank to 1 / 10 or less of the concentration of dissolved flammable gas contained in the culture medium in the culture tank. [Fourth Supplementary Item 11] The culture device according to any one of Fourth Supplementary Item 1 to Fourth Supplementary Item 10, comprising an explosion suppression mechanism that suppresses explosions in a gas recycling path for recycling gas separated from the culture medium.

[0185] The above-mentioned processors include general-purpose processors such as CPUs that execute software (programs) and function as various processing units, as well as programmable logic devices (PLDs) that are processors whose circuit configuration can be changed after manufacture, such as FPGAs (Field Programmable Gate Arrays), and dedicated electrical circuits that are processors with circuit configurations designed specifically for executing specific processes, such as ASICs (Application Specific Integrated Circuits).

[0186] Furthermore, more specifically, the hardware structure of these various processors can be an electric circuit that combines circuit elements such as semiconductor elements.

[0187] The above-described description and illustrations are a detailed explanation of the parts related to the technology of the present disclosure and are merely an example of the technology of the present disclosure. For example, the above description of the configuration, functions, actions, and effects is an explanation of an example of the configuration, functions, actions, and effects of the parts related to the technology of the present disclosure. Therefore, it goes without saying that unnecessary parts may be deleted, new elements may be added, or replacements may be made to the above-described description and illustrations within the scope of the gist of the technology of the present disclosure. Furthermore, to avoid confusion and facilitate understanding of the parts related to the technology of the present disclosure, the above-described description and illustrations omit explanations of common technical knowledge that do not require particular explanation to enable the implementation of the technology of the present disclosure.

[0188] The disclosure of Japanese Patent Application No. 2023-125057, filed on July 31, 2023, is incorporated herein by reference in its entirety. In addition, all documents, patent applications, and technical standards described herein are incorporated herein by reference to the same extent as if each individual document, patent application, and technical standard was specifically and individually indicated to be incorporated by reference.

Claims

1. A culture apparatus for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances, comprising: a culture tank that contains a culture solution for culturing the microorganisms or cells; a raw material gas supply unit that supplies the raw material gas to the culture tank; and a composition ratio control mechanism that measures a composition ratio of a mixed gas in a space present above the liquid surface of the culture solution in the culture tank and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a preset target value outside the explosion range, wherein the dimension of the culture tank satisfies the condition H / DAm≧2, where DAm is the equivalent circle diameter of a cross section perpendicular to the height direction of the culture tank and H is the maximum height of the liquid surface.

2. The culture apparatus according to claim 1, wherein the culture tank is cylindrical and has a bottom.

3. The culture apparatus according to claim 1, wherein the condition is H / DAm≧13.

4. The culture apparatus according to claim 1, wherein the bubble diameter d90 of the raw gas generated in the culture solution is 1000 μm or less.

5. The culture apparatus according to claim 1, further comprising a temperature regulator for regulating the temperature of the culture solution, at least a portion of the temperature regulator being disposed within the culture tank.

6. The culture apparatus according to claim 5, wherein the dimension of the temperature regulator in the height direction of the culture tank is, as a whole, 30% or more of the maximum height of the liquid surface.

7. The culture apparatus according to claim 5, wherein there are a plurality of the temperature regulators, each of the plurality of temperature regulators being disposed at a different position in the height direction of the culture tank.

8. The culture device according to claim 5, further comprising an agitation mechanism having a plurality of agitation parts for agitating the culture solution, the plurality of agitation parts being arranged at different positions in the height direction of the culture tank.

9. The culture apparatus according to claim 8, wherein when the culture apparatus has a plurality of temperature regulators and a plurality of stirring units, a plurality of pairs each of which combines at least one temperature regulator and at least one stirring unit are arranged at different positions in the height direction of the culture tank.

10. The culture apparatus according to claim 1, comprising: a gas circulation path for reusing the mixed gas in the space as the raw gas; and a dissolution rate control mechanism for measuring a combustible gas dissolution rate, which is the proportion of the combustible gas dissolved in the culture liquid among the combustible gas contained in the raw gas supplied to the culture tank through the gas circulation path and the raw gas supply unit during culture, and for maintaining the measured combustible gas dissolution rate at a preset target value.

11. The culture apparatus according to claim 10, wherein the target value of the flammable gas dissolution rate is 90% or more.

12. The culture apparatus of claim 10, wherein the dissolution rate control mechanism further measures a combustible gas consumption rate of the combustible gas consumed by the microorganisms or cells among the combustible gases contained in the raw gas supplied to the culture tank through the gas circulation path or the raw gas supply unit during culture, and maintains the measured combustible gas consumption rate at 90% or more through control of the dissolution rate of the combustible gas.

13. The culture apparatus according to claim 1, wherein the microorganism is a hydrogen oxidizing bacterium, the raw material gas contains hydrogen as the combustible gas and oxygen and carbon dioxide as other components, and the adjustment gas is carbon dioxide.

14. The culture apparatus according to claim 1, further comprising: a first component separation mechanism for separating a specific component from the mixed gas extracted from the culture tank; or a second component separation mechanism for separating a specific component from a separated gas separated from the culture liquid extracted from the culture tank.

15. The culture apparatus according to claim 10, wherein in the gas circulation path, a mixed gas outlet port for extracting the mixed gas from the culture tank is positioned at a position capable of extracting the foam layer present on the liquid surface in the culture tank.

16. The culture apparatus according to claim 1, comprising: a culture medium recovery mechanism for recovering a recovery liquid, which is a portion of the culture medium containing the produced organic matter, from the culture medium removed from the culture tank; a recovery liquid tank for storing the recovery liquid containing the organic matter; and a concentration reduction mechanism for reducing the dissolved combustible gas concentration contained in the recovery liquid stored in the recovery liquid tank to 1 / 10 or less of the dissolved combustible gas concentration contained in the culture medium in the culture tank.

17. The culture apparatus according to claim 1, further comprising an explosion suppression mechanism for suppressing explosions in a gas recycling path for recycling gas separated from the culture solution.

18. A control method for a culture apparatus for culturing microorganisms or cells, comprising a culture tank containing a culture solution for culturing microorganisms or cells that utilize a raw material gas containing a flammable gas for growth or production of organic substances, and a raw material gas supply unit for supplying a raw material gas containing a flammable gas to the culture tank, wherein the dimensions of the culture tank satisfy the condition H / DAm≧2, where DAm is the equivalent circular diameter of a cross section perpendicular to the height direction of the culture tank, and H is the maximum height of the liquid level, and the method measures a composition ratio of a mixed gas in a space present above the liquid level of the culture solution in the culture tank, and supplies an adjustment gas into the space in accordance with the measured composition ratio of the mixed gas, thereby maintaining the composition ratio of the mixed gas in the space at a preset target value outside the explosion range.

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