Fermentation product manufacturing apparatus

Abstract

To provide a method for manufacturing a fermentation product which suppresses an effect of bubbles mixed into fluid to a measurement result of a sensor, prevents accumulation of crystals created in fluid in the vicinity of the sensor, and measures the properties of fluid and solid.SOLUTION: A manufacturing method for creating a fermentation product by a fermentation tank has: a step of preparing a fermentation tank and a sensor device; a step of inputting fluid into the fermentation tank; and a step of operating fermentation of the fermentation tank and measuring the properties of fluid in the fermentation tank, and adjusting an operation condition, where the sensor device has a sensor measuring the properties of fluid and a cover main body for the sensor, a lower permeation part which allows fluid and crystals in fluid to pass is provided for a lower face of the cover main body, and an upper permeation part which allows fluid and crystals in fluid is provided for an upper face of the body, micropores are severally formed in the lower permeation part and the upper permeation part, micropores provided in the upper permeation part have a size of micropores provided in the lower permeation part or more.SELECTED DRAWING: Figure 6

Description

Technical Field

[0001] The present invention relates to a method for producing a fermentation product, and particularly relates to a method for producing a fermentation product, in which a fermentation product is generated by operating a fermenter in which bubbles are mixed and crystals having an average particle diameter of 5 μm or more are formed in the liquid, and a sensor device used therefor.

Background Art

[0002] In the production of various fermentation products, it is necessary to measure various properties of the liquid in the fermenter, such as the electrical conductivity and turbidity of the liquid, and the concentration of specific components contained in the liquid. Japanese Patent No. 3074781 (Patent Document 1) describes a method for producing L-lysine. In this production method, the carbon source is added so that the concentration of the carbon source in the culture solution is maintained at 5 g / L or less. That is, in this method, the carbon source concentration is measured by sampling the culture solution in a timely manner to directly analyze the carbon source concentration, or by measuring the pH and dissolved oxygen concentration, and sensing the deficient state of the carbon source from the changes thereof, so as to control the feeding of the medium.

[0003] As in the invention described in Patent Document 1, it is relatively easy to take out a part of the liquid to be measured from the production process and measure the properties of the liquid, but in-line measurement without taking out the liquid from the production process is preferable from the viewpoint of production efficiency. However, when bubbles are mixed in the liquid to be measured, or when crystals are formed in the liquid, it may be particularly difficult to measure the properties of the liquid in-line. For example, the culture solution subjected to aeration culture is mixed with bubbles of supplied oxygen or air, and bubbles of carbon dioxide which is a metabolite of the microorganism itself during culture, and these bubbles may introduce noise into the measured values or increase measurement errors.

[0004] Japanese Patent Publication No. 4420168 (Patent Document 2) describes a turbidity sensor. This turbidity sensor has a hollow semi-cylindrical member made of stainless steel, with an intake port for the test liquid and an automatically opening and closing swing valve at the bottom, and a hole for removing bubbles at the top. Furthermore, the liquid contact photometric part of a laser turbidimeter is positioned at the tip inside the hollow semi-cylindrical. When measuring with this turbidity sensor, first the swing valve is opened to replace the test liquid inside the hollow semi-cylindrical. Next, the swing valve is closed, and the measurement of turbidity is performed after waiting for the bubbles inside the hollow semi-cylindrical to be discharged through the bubble removal hole and the detected turbidity to stabilize. In the invention described in Patent Document 2, the influence of bubbles in the test liquid is reduced in this way. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Patent No. 3074781 [Patent Document 2] Patent No. 4420168 [Overview of the project] [Problems that the invention aims to solve]

[0006] However, in the turbidity sensor described in Patent Document 2, it is necessary to wait for the detected value to stabilize after closing the swing valve, making real-time detection difficult. Furthermore, when the turbidity sensor is applied to a liquid in which crystals are formed, crystals may accumulate on the movable parts such as the swing valve, potentially causing malfunctions. In addition, the turbidity sensor described in Patent Document 2 has a complex structure because it requires a swing valve that is opened and closed remotely, and maintenance to ensure stable operation over a long period of time is also time-consuming.

[0007] On the other hand, when applying a sensor to a liquid in which crystals are formed, it is necessary not only to suppress the effects of crystal formation but also to analyze the amount of precipitated solid simultaneously with the liquid phase when the concentration of fermentation products in the liquid phase exceeds the solubility limit and precipitates. Here, if a sensor cover is provided to suppress the effects of air bubbles, crystals will accumulate near the sensor and inside the sensor cover, making it difficult to accurately measure the concentration of the product. Therefore, it is necessary to take measures to prevent accumulation, such as appropriately discharging crystals that have precipitated inside the sensor cover, so that the crystal concentration in the fermentation tank and the crystal concentration around the sensor are equal.

[0008] Therefore, the present invention aims to provide a method for producing fermented products and a sensor device used therein, which have a simple structure that suppresses the influence of air bubbles mixed in the liquid on the measurement results of the sensor, and prevents crystals formed in the liquid from accumulating near the sensor or inside the sensor cover, thereby enabling the measurement of the properties of the liquid and solid in the fermentation tank and the operation of fermentation based on those properties. [Means for solving the problem]

[0009] To solve the above-mentioned problems, the present invention provides a method for producing a fermentation product by operating a fermentation tank in which bubbles are mixed and crystals with an average particle size of 5 μm or more are generated in the liquid, comprising the steps of: preparing a fermentation tank and a sensor device for measuring the properties of the liquid in the fermentation tank; adding a liquid to be fermented to the fermentation tank; operating the fermentation tank for fermentation, measuring the properties of the liquid in the fermentation tank with the sensor device, and adjusting the conditions of the fermentation operation based on the measurement results, wherein the sensor device comprises a sensor for measuring the properties of the liquid and a cover body for the sensor arranged to surround the sensor, wherein at least a part of the lower surface of the cover body is provided with a lower permeable portion that allows the liquid and at least a part of the crystals in the liquid to pass through, and at least a part of the upper surface of the cover body is provided with an upper permeable portion that allows the liquid and at least a part of the crystals in the liquid to pass through, wherein a number of micropores for allowing the liquid to pass through are formed in the lower permeable portion and the upper permeable portion, respectively, and the micropores provided in the upper permeable portion are larger than or equal to the micropores provided in the lower permeable portion.

[0010] According to the present invention configured as described above, a sensor device for measuring the properties of the liquid in a fermentation tank has a cover body that surrounds the sensor. The cover body is provided with a lower permeable section and an upper permeable section that allow at least a portion of the liquid and crystals in the liquid to pass through, so that the liquid to be measured can constantly flow into and out of the cover body. As a result, the liquid in the cover body is constantly replaced, and the sensor placed inside the cover body can continuously measure the properties of the liquid in real time. Furthermore, since the lower and upper permeable sections of the cover body allow at least a portion of the crystals in the liquid to pass through, crystals generated in the liquid are less likely to accumulate on the cover body, and fermentation operation can be continued for a long time without maintenance such as cleaning the cover body. In addition, since the micropores provided in the upper permeable section are larger than the micropores provided in the lower permeable section, bubbles rising from below the cover body are less likely to pass through the micropores in the lower permeable section, and the entry of bubbles into the cover body can be effectively suppressed. On the other hand, since the micropores in the upper permeable section are formed to be larger than those in the lower permeable section, air bubbles that enter the cover body rise to the surface and are easily expelled through the upper permeable section. As a result, it is possible to suppress the accumulation of air bubbles inside the cover body, which would otherwise adversely affect the sensor's measurement values.

[0011] In the present invention, preferably, the average diameter of the bubbles mixed in the liquid of the fermentation tank is 50 μm or more. According to the present invention configured in this manner, since the average diameter of bubbles mixed in the liquid of the fermentation tank is 50 μm or more, the cover body can suppress the intrusion of bubbles while allowing crystals with an average particle size of 5 μm or more generated in the liquid to pass through. As a result, stable measurement values ​​can be obtained by the sensor. In this specification, the average diameter of bubbles is the mean value of the weighted chord length obtained by measurement using convergent beam reflectance measurement (FBRM), and corresponds to the so-called volume-based average value.

[0012] In the present invention, preferably, the fermentation tank has a vent pipe for supplying gas into the fermentation tank, and the diameter of the outlet of this vent pipe is 1 μm or more. According to the present invention configured in this way, since the diameter of the pore at the outlet of the vent pipe that supplies gas into the fermentation tank is 1 μm or larger, the average diameter of the bubbles mixed into the liquid in the fermentation tank becomes larger. As a result, the cover body can suppress the intrusion of bubbles while allowing crystals with an average particle size of 5 μm or larger that are generated in the liquid to pass through. As a result, stable measurement values ​​can be obtained by the sensor.

[0013] In the present invention, preferably, the fermenter has a vent pipe for supplying gas into the fermenter, and the volume of gas supplied to the fermenter per hour through this vent pipe is no more than twice the volume of the culture medium at the start of fermentation in the fermenter. According to the present invention configured in this way, the volume of gas sent into the fermentation tank per hour via the vent pipe is less than twice the volume of the culture medium at the start of fermentation. Therefore, the gas can be dissolved into the liquid without excessively subdividing the gas bubbles sent into the fermentation tank. As a result, the entry of bubbles into the cover body can be easily suppressed.

[0014] In the present invention, preferably, the cover body is formed in a substantially cylindrical shape, and the sensor extends in the axial direction inside it. With the present invention configured in this way, since the cover body is formed in a substantially cylindrical shape, bubbles that rise from the lower side of the cover body can easily flow upward along the lower surface of the cover body, further suppressing the entry of bubbles into the cover body. In addition, because the cover body is formed in a substantially cylindrical shape, bubbles that enter the cover body and rise to the surface are collected in the highest part of the cover body, making it less likely for them to come into contact with the sensor. As a result, even if bubbles enter the cover body, the adverse effect on measurement can be minimized.

[0015] In the present invention, preferably, the lower permeable portion is provided across the entire lower semicircular portion of the substantially cylindrical cover body, and the upper permeable portion is provided across the entire upper semicircular portion of the cover body. With the present invention configured in this way, since the entire surfaces of the lower and upper semicircular portions are provided with lower and upper permeable portions, respectively, the area of ​​the cover body through which liquid and crystals can pass is made extremely large. As a result, crystals that enter the cover body are more easily discharged to the outside, and the accumulation of crystals inside the cover body can be suppressed.

[0016] In the present invention, preferably, the cover body is formed from a thin metal plate, and the micropores provided in the lower and upper permeable portions are substantially circular holes made in the thin metal plate. According to the present invention as described above, since micropores are formed in the lower and upper permeable parts by holes provided in a thin metal plate, crystals are less likely to adhere to and accumulate in the lower and upper permeable parts compared to when the lower and upper permeable parts are formed with a mesh-like material formed by weaving strands, thereby improving the maintainability of the sensor cover. Furthermore, by forming micropores in the lower and upper permeable parts by holes provided in a thin metal plate, a cover body that is less prone to damage than a mesh-like material can be constructed, resulting in a more durable cover body.

[0017] In the present invention, preferably, the diameter of the micropores provided in the upper permeable portion is 1 to 5 times the diameter of the micropores provided in the lower permeable portion. In the present invention configured as described above, by setting the diameter of the micropores in the upper permeable section to 1 to 5 times the diameter of the micropores in the lower permeable section, the suppression of air bubbles entering the cover body and the discharge of air bubbles that have entered the cover body are properly balanced, and the influence of air bubbles on the sensor can be effectively suppressed.

[0018] In the present invention, preferably, the diameter of the micropores provided in the lower permeable portion is 540 μm to 750 μm. In the present invention configured in this way, the diameter of the micropores provided in the lower permeable portion is formed to be 540 μm to 750 μm, so that the intrusion of bubbles of a size that would adversely affect the sensor's measurement values ​​can be effectively suppressed while allowing the inflow of liquid and crystals into the cover body.

[0019] In the present invention, preferably, the fermentation product produced by operating the fermenter for fermentation is cysteine, and at least a part of this cysteine is oxidized, whereby cystine accumulates in the fermenter. In the present invention configured as described above, cysteine is produced as a fermentation product in the fermenter, and at least a part of this cysteine is oxidized to produce cystine. Therefore, when the diameter of the micropores provided in the lower permeable portion is set to 540 μm to 750 μm, the crystals of cysteine and cystine in the liquid can flow into and out of the cover body while effectively suppressing the intrusion of air bubbles, and the concentration of cystine can be accurately detected by the sensor.

[0020] In the present invention, preferably, the cover body is provided so as to protrude obliquely downward from the side wall surface of the fermenter containing the liquid, and the measuring portion of the sensor is arranged in the vicinity of the distal end portion of the cover body. In the present invention configured as described above, the cover body protrudes obliquely downward from the side wall surface of the fermenter containing the liquid, so that air bubbles that rise from below and reach the cover body easily flow upward along the lower side surface of the cover body, and intrusion into the cover body can be effectively suppressed. In addition, since air bubbles that have entered the cover body gather at the base end portion of the cover body located above, they move away from the measuring portion of the sensor arranged in the vicinity of the distal end portion of the cover body, and the adverse effect on measurement can be reduced.

[0021] Furthermore, the present invention is a sensor device for measuring the characteristics of a liquid in a fermenter, in which bubbles are mixed and crystals with an average particle size of 5 μm or more are formed in the liquid, the sensor device comprising: a sensor for measuring the characteristics of the liquid; and a cover body for the sensor arranged so as to surround the sensor, wherein at least a part of the lower surface of the cover body is provided with a lower permeable portion that allows at least a part of the liquid and the crystals in the liquid to pass through, at least a part of the upper surface of the cover body is provided with an upper permeable portion that allows at least a part of the liquid and the crystals in the liquid to pass through, the lower permeable portion and the upper permeable portion are each formed with a large number of fine pores for allowing the liquid to pass through, and the fine pores provided in the upper permeable portion are characterized by having a size equal to or larger than the fine pores provided in the lower permeable portion. Effects of the Invention

[0022] According to the method for producing a fermentation product and the sensor device used therein of the present invention, with a simple structure, it is possible to suppress the influence of bubbles mixed in the liquid on the measurement result of the sensor, prevent crystals formed in the liquid from depositing in the vicinity of the sensor or inside the sensor cover, measure the characteristics of the liquid and solid in the fermenter, and perform fermentation operation based thereon. Brief Description of the Drawings

[0023] [Figure 1] It is a cross-sectional view showing an example in which the sensor device used for carrying out the method for producing a fermentation product according to the embodiment of the present invention is applied to a fermenter. [Figure 2] It is a perspective view showing the external appearance of the cover body for the sensor provided in the sensor device according to the embodiment of the present invention. [Figure 3] It is an enlarged cross-sectional view showing a state where the sensor device according to the embodiment of the present invention is attached to the side wall surface of the fermenter. [Figure 4] It is an enlarged view showing an example of the fine pores provided on the surface of the cover body in the sensor device according to the embodiment of the present invention. [Figure 5] It is a diagram schematically showing the action of the sensor cover in the sensor device according to the embodiment of the present invention. [Figure 6] This flowchart shows the procedure for producing a fermentation product according to an embodiment of the present invention. [Figure 7] This figure shows an example of a measurement performed without using a sensor cover. [Figure 8] This figure shows an example of measurement using a sensor device with an appropriate sensor cover. [Figure 9] This figure shows an example of a measurement performed using a sensor cover with excessively fine pores. [Figure 10] This diagram shows the condition of various sensor covers after use. [Modes for carrying out the invention]

[0024] Next, preferred embodiments of the present invention will be described with reference to the attached drawings. Figure 1 is a cross-sectional view showing an example of applying a sensor device used to carry out a method for producing fermentation products according to an embodiment of the present invention to a fermentation tank. Figure 2 is a perspective view showing the external appearance of the sensor cover body provided in the sensor device according to an embodiment of the present invention. Figure 3 is an enlarged cross-sectional view showing the sensor device according to an embodiment of the present invention attached to the side wall of a fermentation tank.

[0025] As shown in Figure 1, the sensor device 1 according to an embodiment of the present invention is installed on the side wall surface 2a of a fermentation tank 2, which is a container for liquid, and is configured to measure the concentration of amino acids in the culture medium L, which is the liquid contained in the fermentation tank 2, in line. Furthermore, a sensor is placed inside the sensor device 1, and the signal acquired by this sensor is transmitted to the measuring instrument body 4. In this embodiment, the fermentation tank 2 is generally cylindrical, and a stirrer 6 is provided along its central axis for stirring the culture medium. The stirrer 6 is equipped with a plurality of blades 6a for stirring the culture medium L, and by rotating these blades 6a, the culture medium L in the fermentation tank 2 is stirred to become homogeneous.

[0026] Furthermore, in this embodiment, since aeration culture is performed in the fermentation tank 2, a sparger 8, which is a vent pipe, is provided at the bottom of the fermentation tank 2, and oxygen or air is introduced into the fermentation tank 2 from the supply device 8a via the sparger 8. Consequently, the culture medium L contains fine bubbles of the supplied oxygen or air, and fine bubbles of carbon dioxide produced by the cultured microorganisms. In this embodiment, the diameter of the outlet of the sparger 8 that discharges gas is approximately 6 mm, and as a result, bubbles with an average diameter of approximately 250 μm are mixed into the culture medium in the fermentation tank 2. Preferably, the diameter of the pores for discharging gas provided in the sparger 8, etc., is set to approximately 5 μm to approximately 36 μm, and bubbles with an average diameter of approximately 150 μm to approximately 350 μm are mixed into the culture medium in the fermentation tank 2. Alternatively, a FAD (Fine Air Diffuser) can be used as a vent pipe for mixing bubbles into the culture medium. The FAD has numerous pores ranging in size from approximately 1 μm to 20 μm, which allows for the introduction of air bubbles with an average diameter of approximately 50 μm to 250 μm into the culture medium.

[0027] Next, the configuration of the sensor device 1 according to an embodiment of the present invention will be described with reference to Figures 2 and 3. As shown in Figure 3, the sensor device 1 comprises a sensor cover 10 according to an embodiment of the present invention and a sensor 12 disposed inside the sensor cover 10.

[0028] The sensor cover 10 has a substantially cylindrical cover body 14 and a flange portion 16 provided at the base end of the cover body 14 and fixed to the side wall surface 2a of the fermentation tank 2. The cover body 14 is made of a thin stainless steel plate and is configured in a substantially cylindrical shape with a closed end, and is positioned to surround the sensor 12. Furthermore, as will be described later, the cover body 14 has numerous micropores on its entire surface, and the liquid and at least some of the crystals in the fermentation tank 2 can flow into the cover body 14 through these micropores. The cover body can be configured in any shape other than cylindrical, such as a rectangular parallelepiped. In addition, the cover body can be made of a metal other than stainless steel or a resin such as polytetrafluoroethylene, and it is preferable to use a material that is less likely to be damaged by the flow of liquid due to stirring.

[0029] The flange portion 16 is a stainless steel disc, to which the cover body 14 is fixed and integrated by welding. The cover body 14 is mounted perpendicular to the plate surface of the flange portion 16. The flange portion 16 is provided with bolt holes 16a, and the flange portion 16 is fixed to the outside of the side wall surface 2a by fixing bolts 18a. A packing 18b is placed between the flange portion 16 and the side wall surface 2a to ensure watertightness between the flange portion 16 and the side wall surface 2a. Furthermore, as shown in Figure 3, the portion on the outside of the side wall surface 2a to which the flange portion 16 is fixed is formed to be inclined with respect to the vertical. As a result, when the sensor device 1 is attached to the side wall surface 2a of the fermentation tank 2, the cover body 14 protrudes diagonally downward and inward from the side wall surface of the container. The mounting angle of the cover body 14 is preferably set to an angle that suppresses the inflow of air bubbles into the cover body 14 and also suppresses the formation of liquid puddles near the cover body 14, which can lead to the growth of bacteria. Depending on the properties of the liquid, it may also be set to an angle close to horizontal. In this embodiment, the central axis of the cover body 14 is inclined at approximately 16 degrees with respect to the horizontal axis.

[0030] Furthermore, in this embodiment, a transmission-reflection near-infrared spectrometer (NIR sensor) is used as the sensor 12, and the concentration of amino acids in the culture medium L is measured by near-infrared analysis. However, the sensor cover 10 in this embodiment can be applied to various sensors other than NIR sensors, such as spectrometers using ultraviolet or visible light, other optical sensors, sensors using focused beam reflectivity (FBRM) to measure crystal particle size, and electromagnetic sensors to measure dielectric constant and conductivity, and a sensor device can be constructed by combining these sensors.

[0031] As shown in Figure 3, the sensor 12 is equipped with a rod-shaped sensor probe 12a with a circular cross-section, and a measuring section 12b is provided at its tip. The sensor probe 12a extends axially into the interior of the cover body 14 through an opening provided in the center of the flange portion 16 of the sensor cover 10. The sensor probe 12a also extends along the central axis of the cover body 14, and the measuring section 12b provided at its tip is located near the tip of the cover body 14. In this embodiment, the outer diameter of the sensor probe 12a is approximately 20 mm, and the cover body 14, with an outer diameter of approximately 60 mm, surrounds it. Thus, it is preferable to provide a clearance of approximately 10 mm to approximately 30 mm between the sensor probe 12a and the inner wall surface of the cover body 14.

[0032] Next, with further reference to Figures 4 and 5, the configuration of the cover body 14 provided in the sensor cover 10 of the embodiment of the present invention will be described in detail. Figure 4 is a magnified view showing an example of micropores provided on the surface of the cover body 14. Figure 5 is a schematic diagram illustrating the function of the sensor cover.

[0033] As described above, the cover body 14 of the sensor device 1 according to the embodiment of the present invention has numerous micropores formed on its entire surface, allowing at least a portion of the surrounding liquid and crystals to flow into the inside of the cover body 14. In this embodiment of the sensor device 1, it is preferable to set the size of each micropore provided on the upper surface of the cover body 14 to be greater than or equal to the size of each micropore provided on the lower surface. That is, the lower surface of the cover body 14 is provided with a lower permeable section 14a for liquid to pass through, and the upper surface is provided with an upper permeable section 14b for liquid to pass through, and the micropores provided in the upper permeable section 14b are formed to be the same size as, or larger than, the micropores provided in the lower permeable section 14a.

[0034] As shown in Figure 2, the lower permeable portion 14a is formed across the entire lower semicircular portion of the cover body 14, which has a circular cross-section, and the upper permeable portion 14b is formed across the entire upper semicircular portion of the cover body 14, which has an upper semicircular portion. In addition, the tip surface 14c of the cover body 14 also has numerous micropores, identical to those in the lower permeable portion 14a, formed across its entire surface.

[0035] In this specification, the "lower surface" of the cover body 14 refers to the surface that is illuminated when light is projected vertically downwards onto the sensor cover 10 when it is installed in use, and the "upper surface" refers to the surface that is illuminated when light is projected vertically upwards. In this embodiment, numerous micropores are formed on the entire "lower surface" and "upper surface" of the cover body 14, but the micropores do not necessarily need to be formed on the entire surface; they may be formed on only a part of it. Furthermore, in this embodiment, micropores are also provided on the tip surface 14c of the cover body 14, but it is not necessary to provide micropores on the tip surface 14c.

[0036] Next, as shown in Figure 4, the lower transparent section 14a and the upper transparent section 14b are arranged in a staggered pattern with approximately circular micropores. That is, each micropore is arranged such that the lines connecting the centers of three adjacent micropores form an equilateral triangle. In this embodiment, the lower transparent section 14a and the upper transparent section 14b are constructed by etching a thin stainless steel plate to form a large number of micropores. As an example, in this embodiment, the lower transparent section 14a is formed by arranging circular holes with a diameter D of approximately 750 μm at a pitch P of approximately 1070 μm (the length of the sides of an equilateral triangle connecting the centers of the circles). Similarly, in this embodiment, the upper transparent section 14b is also constructed from circular holes with a diameter D of approximately 750 μm arranged at a pitch P of approximately 1070 μm.

[0037] Here, the lower permeable section 14a and upper permeable section 14b, which have circular holes with a diameter D of approximately 750 μm arranged at a pitch P of approximately 1070 μm, have an aperture ratio of approximately 44.4%, which is roughly equivalent to a 20# mesh (20 mesh: a mesh formed by arranging 20 strands vertically and horizontally within 1 inch). In this specification, the "size of the micropores" in the lower permeable section 14a and upper permeable section 14b refers to the diameter of the circular holes.

[0038] For example, if circular holes with a diameter D of approximately 540 μm are arranged at a pitch P of approximately 770 μm, the aperture ratio will be approximately 44.5%, which is roughly equivalent to a mesh of size 30. If circular holes with a diameter D of approximately 350 μm are arranged at a pitch P of approximately 630 μm, the aperture ratio will be approximately 28%, which is roughly equivalent to a mesh of size 40. If circular holes with a diameter D of approximately 250 μm are arranged at a pitch P of approximately 360 μm, the aperture ratio will be approximately 43.6%, which is roughly equivalent to a mesh of size 60. If circular holes with a diameter D of approximately 180 μm are arranged at a pitch P of approximately 320 μm, the aperture ratio will be approximately 28.7%, which is roughly equivalent to a mesh of size 80. When circular holes with a diameter D of approximately 150 μm are arranged at a pitch P of approximately 250 μm, the aperture ratio is approximately 32.5%, which is roughly equivalent to a 100♯ mesh. When circular holes with a diameter D of approximately 100 μm are arranged at a pitch P of approximately 210 μm, the aperture ratio is approximately 20.5%, which is roughly equivalent to a 150♯ mesh.

[0039] In this embodiment, the lower permeable portion 14a and the upper permeable portion 14b are formed by creating numerous micropores in a thin plate. However, the lower permeable portion 14a and the upper permeable portion 14b can also be formed by a mesh-like material created by weaving or braiding thin wires together. In this case, "micropores" are formed as spaces between the wires constituting the mesh-like material, and "size of micropores" refers to the distance between adjacent wires. Preferably, the diameter of the micropores provided in the lower permeable portion 14a is set to approximately 180 μm to approximately 750 μm. More preferably, the diameter of the micropores provided in the lower permeable portion 14a is set to approximately 250 μm to approximately 750 μm. Even more preferably, the diameter of the micropores provided in the lower permeable portion 14a is set to approximately 350 μm to approximately 750 μm. Even more preferably, the diameter of the micropores provided in the lower permeable portion 14a is set to approximately 540 μm to approximately 750 μm. In other words, it is preferable to set the diameter of the micropores provided in the lower permeable portion 14a to a size that suppresses the entry of air bubbles in the culture medium L while allowing at least a portion of the crystals in the culture medium L to pass through. Furthermore, the lower permeable portion 14a and the upper permeable portion 14b, which have numerous micropores formed in a thin plate, are less prone to crystal adhesion and accumulation, thereby improving the maintainability of the sensor cover.

[0040] Furthermore, in order to facilitate the discharge of air bubbles that have entered the cover body, it is preferable that the micropores provided in the upper permeable portion 14b be formed to be larger than or equal to the size of the micropores in the lower permeable portion. However, the diameter of the micropores in the upper permeable portion 14b should be set to a diameter that sufficiently suppresses the inflow of air bubbles through the upper permeable portion 14b due to the downward flow of liquid. Preferably, the diameter of the micropores provided in the upper permeable portion 14b is set to approximately 1 to approximately 5 times the diameter of the micropores provided in the lower permeable portion 14a. This makes it possible to properly balance the suppression of air bubble intrusion into the cover body 14 with the discharge of air bubbles that have entered the cover body 14.

[0041] Next, the function of the sensor cover will be schematically explained with reference to Figure 5. First, when measuring the properties of a liquid containing air bubbles, it is conventionally known that covering the sensor with a mesh strainer reduces the influence of the bubbles. However, as shown in Figure 5(a), if crystals are present in the culture medium L, setting the size of the micropores in the cover body 14 (lower permeable section 14a, upper permeable section 14b) too finely to prevent the entry of air bubbles will prevent both air bubbles B and crystals C from entering the strainer. In such cases, the sensor cannot measure the components of the crystals, making accurate measurement impossible.

[0042] On the other hand, as shown in Figure 5(b), if the size of the micropores in the cover body 14 that covers the sensor is set to an appropriate size, the intrusion of air bubbles B can be suppressed, while at least a portion of the crystal C can penetrate into the interior of the cover body 14, making it possible to measure the components of the crystal with the sensor.

[0043] More preferably, as shown in Figure 5(c), small diameter micropores are formed in the lower permeable portion 14a of the cover body 14, and larger micropores than those in the lower permeable portion 14a are formed in the upper permeable portion 14b. By forming the cover body 14 in this way, the entry of large bubbles rising from below into the cover body 14 is prevented. In addition, at least a portion of the crystals in the culture medium L enters the cover body 14 through the lower permeable portion 14a and is detected by the sensor. Furthermore, as shown in Figure 5(c), by providing the cover body 14 so as to protrude diagonally downward from the side wall surface 2a of the fermentation tank 2, bubbles that are prevented from entering by the cover body 14 can easily move diagonally upward along the lower surface of the cover body 14, and many bubbles B can easily bypass the sensor cover 10 and move upward.

[0044] On the other hand, small bubbles approaching from below can enter the cover body 14 through the lower permeable section 14a. However, by forming large-diameter micropores in the upper permeable section 14b, small bubbles that enter through the lower permeable section 14a float up inside the cover body 14 and are easily discharged outside the cover body 14 through the upper permeable section 14b. This prevents the invading bubbles from remaining inside the cover body 14 for a long time and growing into large bubbles.

[0045] Furthermore, although not all bubbles approaching the sensor cover 10 approach from below, a large proportion of bubbles approach the sensor cover 10 from below because bubbles are always subjected to buoyancy from the liquid, and the intrusion of these bubbles is significantly suppressed by the lower permeable section 14a. In addition, the upper permeable section 14b also more effectively prevents the intrusion of some bubbles approaching the sensor cover 10 from above or the sides due to the flow of liquid caused by stirring in the fermentation tank than if the top of the cover were a complete opening. Moreover, by making the micropores of the upper permeable section 14b larger, crystal C can more easily penetrate into the interior of the sensor cover 10, and the crystalline components can be detected more accurately.

[0046] Furthermore, by positioning the cover body 14 to protrude diagonally downward, air bubbles that enter the cover body 14 move upward toward the base end of the cover body 14. On the other hand, since the measuring section 12b of the sensor probe 12a, which is located inside the cover body 14, is positioned near the tip of the cover body 14, air bubbles inside the cover body 14 are moved away from the measuring section 12b of the sensor 12. This further reduces the influence of air bubbles that enter the cover body 14 on the measurement. Due to these effects, the sensor cover 10 of this embodiment effectively reduces the influence of air bubbles on the measurement.

[0047] Next, with reference to Figures 6 to 10, a method for producing fermentation products using the sensor device 1 according to an embodiment of the present invention will be described. Figure 6 is a flowchart showing the procedure for producing a fermentation product according to an embodiment of the present invention. Figure 7 is a diagram showing an example of measurement performed without using the sensor cover 10. Figure 8 is a diagram showing an example of measurement by the sensor device 1 using an appropriate sensor cover 10. Figure 9 is a diagram showing an example of measurement performed using a sensor cover 10 with excessively fine pores. Furthermore, Figure 10 shows the state of various sensor covers 10 after use.

[0048] First, in step S1 of Figure 6, a fermentation tank 2 and a sensor device 1 for measuring the properties of the liquid in the fermentation tank 2 are prepared. In this embodiment, a sparger 8 is provided inside the fermentation tank 2, and an air supply device 8a is connected to the sparger 8. Here, the sensor cover 10 used for the sensor device 1 is selected to have micropores of an appropriate size according to the average particle size of the crystals generated in the fermentation tank 2. In addition, multiple sensor devices 1 can be provided for one fermentation tank 2 depending on the required measurement items.

[0049] Next, in step S2, the liquid to be fermented in fermenter 2 is added to fermenter 2. In this example, by fermenting the culture medium L added to fermenter 2, cysteine ​​is produced as a fermentation product, and at least a portion of this cysteine ​​is oxidized in the culture medium to produce cystine (Cys2) as the final fermentation product. For example, the culture medium L contains a carbon source, a nitrogen source, a sulfur source, and inorganic ions.

[0050] As carbon sources, sugars such as glucose, fructose, sucrose, molasses, and hydrolyzed starch, as well as organic acids such as fumaric acid, citric acid, and succinic acid can be used. As nitrogen sources, inorganic ammonium salts such as ammonium sulfate, ammonium chloride, and ammonium phosphate, organic nitrogen such as soybean hydrolysate, ammonia gas, and ammonia water can be used. Sources of sulfur include inorganic sulfur compounds such as sulfates, sulfites, sulfides, hyposulfites, and thiosulfates. As organic trace nutrients, it is desirable to include appropriate amounts of essential substances such as vitamin B1 or yeast extract. In addition to these, small amounts of potassium phosphate, magnesium sulfate, iron ions, manganese ions, etc. may be added as needed.

[0051] In step S3, the fermentation tank 2 into which the culture medium L has been introduced is operated for fermentation, and the characteristics of the liquid in the fermentation tank 2 are measured by the sensor device 1. During fermentation, the culture medium L in the fermentation tank 2 is stirred by operating the agitator 6, and air bubbles are mixed into the culture medium L via the sparger 8 by operating the supply device 8a. In this embodiment, the average diameter of the air bubbles mixed into the culture medium L by the sparger 8 is approximately 250 μm. The volume of air introduced per hour corresponds to approximately 0.1 to 1.2 times the volume of the culture medium at the start of fermentation in the fermentation tank 2. Preferably, by setting the volume of air supplied to the fermentation tank 2 per hour to 1 to 1.2 times or less the volume of the culture medium at the start of fermentation in the fermentation tank 2, air can be dissolved into the liquid without excessively subdividing the air bubbles.

[0052] Furthermore, the conditions for fermentation operation are adjusted based on the measurement results from the sensor device 1. In this embodiment, cystine is produced by the fermentation operation, and as the amount of cystine dissolved in the culture medium L increases, it precipitates, and cystine crystals are formed. The characteristics of the culture medium L during fermentation operation are measured continuously by the sensor device 1. In this embodiment, the characteristics of the culture medium L measured by the sensor device 1 include the concentration of cystine [g / L], as well as the sugar concentration [g / L] (RS), the concentration of ammonia nitrogen (AN), the concentrations of S2O3 [g / L], and the turbidity of the culture medium L (OD).

[0053] Furthermore, the fermentation conditions are adjusted based on the characteristics of the culture medium L measured by the sensor device 1. These adjustments include the temperature of the culture medium L, the pH of the culture medium L, the amount of aeration supplied through the sparger 8, the amount of added sugar solution, and the amount of added phosphorus and other culture medium components. This adjustment of fermentation conditions based on the measured characteristics of the culture medium L is performed as needed during the fermentation process.

[0054] Next, we will explain how to measure cystine concentration using sensor device 1. As described above, the sensor device 1 is equipped with a sensor 12 (Figure 3). In this embodiment, the sensor 12 is an NIR sensor, and the light received by the sensor probe 12a is guided to the measuring instrument body 4 (Figure 1) via an optical fiber. In the measuring instrument body 4, the NIR spectrum of the guided light is acquired. By applying a pre-created calibration model to the NIR spectrum obtained for the light from the sensor probe 12a, the concentration of cystine and other substances contained in the culture medium L can be estimated. Figures 7 to 9 are graphs showing the temporal change in the cystine concentration estimated in this way.

[0055] Figure 7 shows an example of measuring (estimating) the cystine concentration in the culture medium L in the fermenter 2 using the sensor 12 without attaching the sensor cover 10. As shown in Figure 7, although there is a tendency for the concentration of cystine produced in the fermenter 2 to increase over time when the sensor cover 10 is not used, the estimated value fluctuates greatly with each measurement. This is thought to be because air bubbles mixed in the culture medium L affect the light received by the sensor probe 12a, causing the estimated value to vary.

[0056] Figure 8 shows an example of an estimated value when the cystine concentration in the culture medium L, measured in the example shown in Figure 7, is measured using a sensor device 1 equipped with a sensor cover 10. In the example shown in Figure 8, a sensor cover 10 is used in which micropores equivalent to 20# are formed in the lower permeable section 14a and the upper permeable section 14b, respectively. As shown in Figure 8, when a sensor cover 10 with micropores equivalent to 20# is used, the estimated cystine concentration shows the same trend as when the sensor cover 10 is not used.

[0057] In addition, in the example shown in Figure 8, the fluctuation in the estimated cystine concentration is smaller compared to the example shown in Figure 7, indicating that the cystine concentration is measured stably. This is thought to be because the sensor cover 10 surrounding the sensor 12 suppresses the influence of air bubbles mixed in the culture medium L, resulting in stable measurement values. Furthermore, cystine has low solubility in the culture medium L, and much of the cystine produced in the fermenter 2 precipitates and crystallizes. The average particle size of this crystallized cystine is 5 μm or larger, but it can be seen that crystallized cystine is detected even with the sensor cover 10 attached to the sensor 12. In other words, the lower permeable portion 14a and the upper permeable portion 14b of the sensor cover 10 allow at least a portion of the culture medium L and the crystals in the culture medium L to pass through.

[0058] Figure 9 shows an example of measuring the cystine concentration of culture medium L, as measured in the example shown in Figure 8, using a sensor cover 10 with smaller micropores than in Figure 8. In the example shown in Figure 9, a sensor cover 10 is used in which micropores equivalent to 60# are formed in the lower permeable section 14a and the upper permeable section 14b, respectively. In the example shown in Figure 9, immediately after the start of fermentation, a stable estimated value of the cystine concentration is obtained, similar to the example shown in Figure 8, but the fluctuation of the estimated value becomes large over time. As more time passes, abnormal values ​​appear in the estimated value, and eventually the cystine concentration becomes impossible to estimate. This is because scaling of cystine crystals occurs on the outside of the sensor cover 10 during fermentation, and crystals accumulate on the inside of the sensor cover 10.

[0059] In other words, for the fermentation operation that generates cystine in the culture medium L in the fermentation tank 2, the sensor cover 10 with micropores equivalent to 60# had pores that were too fine, and it is thought that the crystals precipitated from the liquid phase could not be discharged from the cover, resulting in the accumulation and retention of crystals. In contrast, in the example shown in Figure 8, even after prolonged fermentation operation, virtually no crystal accumulation occurred on the sensor cover 10, indicating that the sensor cover 10 with micropores equivalent to 20# is appropriate for the fermentation operation that generates cystine.

[0060] Furthermore, in the examples shown in Figures 8 and 9, the lower permeable portion 14a and the upper permeable portion 14b of the sensor cover 10 were provided with micropores of the same size. However, the size of the micropores in the upper permeable portion 14b can also be made larger than the size of the micropores in the lower permeable portion 14a. In this case, air bubbles that enter the interior of the sensor cover 10 can be more easily expelled through the upper permeable portion 14b, and thus the adverse effect of the entering air bubbles on the measurement values ​​can be expected to be further reduced. For example, the micropores in the upper permeable portion 14b of the sensor cover 10 used for measurement shown in Figure 8 may be changed to a size equivalent to 10# to 15#, which is larger than the micropores in the lower permeable portion 14a.

[0061] Next, with reference to Figure 10, the crystal deposition state when measurements are taken using various sensor covers 10 will be explained. Figure 10 is a table summarizing the experimental results regarding the crystal deposition state and the stability of the obtained measurement data when various sensor covers 10 were used.

[0062] As shown in Figure 10, the experiment was conducted under two conditions: condition (1) without using the sensor cover 10, and conditions (2) to (5) using sensor covers 10 equivalent to 20#, 30#, 40#, and 60# respectively. Furthermore, under condition (6), the experiment was also conducted with the lower permeable portion 14a of the sensor cover 10 equivalent to 80# and the upper permeable portion 14b equivalent to 40#. In the experiment, the state of crystal deposition on the sensor 12 and sensor cover 10 was observed after fermentation operation for a predetermined time under each condition.

[0063] First, as shown in Figure 10, when the sensor cover 10 under condition (1) was not used, no crystal adhesion (crystal scaling) was observed on the sensor 12. However, the estimated cystine concentration fluctuated greatly, and stable data could not be measured. In other words, when the sensor cover 10 is not provided, crystallized cystine can also be measured by the sensor 12. However, due to the influence of air bubbles mixed in the culture medium L, a large amount of noise is introduced into the estimated cystine concentration, causing large fluctuations (hunting) in the estimated value.

[0064] Next, when using sensor covers 10 equivalent to 20# under condition (2) and 30# under condition (3), no crystal adhesion to the outer surface of the sensor 12 or sensor cover 10, nor any crystal retention (crystal accumulation) within the sensor cover 10 was observed. Furthermore, there were no significant fluctuations in the estimated cystine concentration, and stable data could be measured. In other words, when the sensor cover 10 is set to the equivalent of 20# or 30#, the size of the micropores is sufficiently larger than the average particle size of the cystine crystals, allowing the cystine crystals to penetrate sufficiently into the sensor cover 10. In addition, the cystine crystals that penetrate into the sensor cover 10 are detected by the sensor 12, providing a highly reliable estimate of the cystine concentration, and the crystals that penetrate into the sensor cover 10 easily flow out of the sensor cover 10. On the other hand, most of the air bubbles mixed in the culture medium L are prevented from entering the sensor cover 10, suppressing the adverse effects of air bubbles on the sensor 12.

[0065] Next, when using the sensor cover 10 equivalent to 40# under condition (4), no crystals were observed to adhere to the outer surfaces of the sensor 12 and the sensor cover 10, but a small amount of crystals were observed to accumulate inside the sensor cover 10. Furthermore, there were no significant fluctuations in the estimated cystine concentration during the experimental period, and stable data could be measured. However, under these conditions, if the fermentation operation is performed for a longer period, there is a risk that the amount of crystals accumulating inside the sensor cover 10 will increase, making it impossible to obtain accurate measurements. Thus, when the micropores provided in the sensor cover 10 are small, the entry of air bubbles into the sensor cover 10 can be suppressed more strongly, which is advantageous in eliminating the adverse effects of air bubbles. On the other hand, when the micropores are small, cystine crystals that enter the sensor cover 10 or crystals generated inside the cover are less likely to be discharged to the outside, and crystals tend to accumulate inside the sensor cover 10.

[0066] Furthermore, when using the sensor cover 10 equivalent to 60# under condition (5), crystal adhesion was observed on the outer surfaces of the sensor 12 and the sensor cover 10, and a large amount of crystals were also observed to accumulate inside the sensor cover 10. In addition, due to the influence of the crystals accumulated inside the sensor cover 10, it became impossible to obtain proper data midway through the experiment. Thus, using a sensor cover 10 with even finer pores than under condition (4) is more effective in suppressing the entry of air bubbles, but the amount of cystine crystals that accumulate inside the sensor cover 10 increases significantly. When a large amount of cystine crystals accumulate inside the sensor cover 10 in this way, the cystine concentration inside the sensor cover 10 becomes significantly high, making it difficult to accurately measure the cystine concentration of the culture medium L in the fermentation tank 2.

[0067] Finally, in condition (6), when the lower permeable portion 14a of the sensor cover 10 was set to an 80# equivalent and the upper permeable portion 14b to an 40# equivalent, no crystal adhesion was observed on the outer surfaces of the sensor 12 and the sensor cover 10, but a small amount of crystal retention was observed inside the sensor cover 10. Furthermore, there were no significant fluctuations in the estimated cystine concentration during the experimental period, and stable data could be measured. However, under this condition, if the fermentation operation is performed for a longer period, there is a risk that the amount of crystal retention inside the sensor cover 10 will increase, making it impossible to obtain accurate measurements. In addition, in condition (6), better results were obtained than in condition (5), even though the micropores of the lower permeable portion 14a were set to an 80# equivalent, which is finer than in condition (5). That is, in condition (6), it is thought that the micropores of the upper permeable portion 14b are larger than in condition (5), making it less likely for crystals to accumulate inside the sensor cover 10. Therefore, by fine-tuning the size of the micropores in the sensor cover 10 under condition (6), it may be possible to construct a sensor cover 10 that can measure stable data over a long period of time while further reducing the adverse effects of air bubbles by using the lower permeable portion 14a of the fine micropores.

[0068] As shown in Figure 10, the results indicate that for fermentation operations that produce cystine in the culture medium L within the fermentation tank 2, a sensor cover 10 with micropores equivalent to 20# and 30# is suitable. Figure 10 shows the results when cystine is produced as a fermentation product in the fermentation tank 2. However, when producing other fermentation products that generate crystals, a sensor cover 10 with micropores of an appropriate size should be designed according to the average particle size of the crystals produced and the average diameter of the bubbles mixed in the culture medium L.

[0069] According to the method for producing fermentation products of the embodiment of the present invention, the sensor device 1 for measuring the properties of the culture medium L, which is the liquid in the fermentation tank 2, has a cover body 14 arranged to surround the sensor 12 (Figure 3). The cover body 14 is provided with a lower permeable portion 14a and an upper permeable portion 14b that allow at least a portion of the culture medium L and the crystals in the culture medium L to pass through, so that the culture medium L to be measured can constantly flow into and out of the cover body 14. As a result, the culture medium L inside the cover body 14 is constantly replaced, and the sensor 12 placed inside the cover body 14 can continuously measure the properties of the culture medium L containing crystals in real time.

[0070] Furthermore, since the lower permeable portion 14a and the upper permeable portion 14b of the cover body 14 allow at least a portion of the crystals in the culture medium L to pass through, crystals generated in the culture medium L are less likely to accumulate on the cover body 14, and fermentation operation can be continued for a long time without maintenance such as cleaning the cover body 14. In addition, since the micropores provided in the upper permeable portion 14b are larger than the micropores provided in the lower permeable portion 14a, bubbles rising from below the cover body 14 are less likely to pass through the micropores of the lower permeable portion 14a, effectively suppressing the entry of bubbles into the cover body 14. On the other hand, since the micropores of the upper permeable portion 14b are formed to be larger than the micropores of the lower permeable portion 14a, bubbles that enter the cover body 14 float up inside the cover body 14 and are easily discharged through the upper permeable portion 14b. As a result, it is possible to suppress bubbles that enter the cover body 14 from remaining inside the cover body 14 and adversely affecting the measurement values ​​of the sensor 12.

[0071] Furthermore, according to the method for producing the fermentation product of this embodiment, since the average diameter of the bubbles mixed in the culture medium L of the fermentation tank 2 is 250 μm, the cover body 14 can suppress the intrusion of bubbles while allowing crystals with an average particle diameter of 5 μm or more generated in the liquid to pass through. As a result, stable measurement values ​​can be obtained by the sensor 12.

[0072] Furthermore, according to the method for producing the fermentation product of this embodiment, since the diameter of the outlet of the vent pipe that supplies gas into the fermentation tank 2 is 6 mm, the average diameter of the bubbles mixed into the culture medium L in the fermentation tank 2 becomes larger. As a result, the cover body 14 can suppress the intrusion of bubbles while allowing crystals with an average particle size of 5 μm or more that are generated in the culture medium L to pass through. As a result, stable measurement values ​​can be obtained by the sensor 12.

[0073] Furthermore, according to the method for producing the fermentation product of this embodiment, the volume of air, which is the gas sent into the fermentation tank 2 per hour via the sparger 8, which is the aeration pipe, is 0.1 to 1.2 times the volume of the culture medium at the start of fermentation. As a result, the air bubbles sent into the fermentation tank 2 can be dissolved into the culture medium L without excessive fragmentation. Consequently, the entry of bubbles into the cover body 14 can be easily suppressed.

[0074] Furthermore, according to the method for producing the fermentation product of this embodiment, since the cover body 14 is formed in a substantially cylindrical shape (Figure 2), bubbles that rise from the bottom of the cover body 14 can easily flow upward along the lower surface of the cover body 14, further suppressing the entry of bubbles into the cover body 14. Also, because the cover body 14 is formed in a substantially cylindrical shape, bubbles that enter the cover body 14 and rise are collected in the highest part of the cover body 14, making it less likely for them to come into contact with the sensor 12. As a result, even if bubbles enter the cover body 14, the adverse effect on measurement can be minimized.

[0075] Furthermore, in the method for producing the fermentation product of this embodiment, since the lower permeable portion 14a and the upper permeable portion 14b are provided on the entire surface of the lower semicircular portion and the upper semicircular portion, respectively, the area through which the culture medium L and crystals permeate the cover body 14 can be made extremely large. As a result, crystals that enter the cover body 14 are more easily discharged to the outside, and the accumulation of crystals inside the cover body 14 can be suppressed.

[0076] Furthermore, according to the method for producing the fermentation product of this embodiment, the micropores of the lower permeable portion 14a and the upper permeable portion 14b are formed by holes provided in a thin metal plate (Figure 4). Compared to the case where the lower permeable portion 14a and the upper permeable portion 14b are formed with a mesh-like material formed by weaving strands, crystals are less likely to adhere to and accumulate in the lower permeable portion 14a and the upper permeable portion 14b, improving the maintainability of the sensor cover 10. In addition, by forming the micropores of the lower permeable portion 14a and the upper permeable portion 14b with holes provided in a thin metal plate, a cover body 14 that is less prone to damage and has higher durability than a mesh-like material can be constructed.

[0077] Furthermore, in the method for producing the fermentation product of this embodiment, if the diameter of the micropores in the upper permeable section 14b is set to be larger than the diameter of the micropores in the lower permeable section 14a, it is possible to effectively suppress the entry of air bubbles into the cover body 14 while promoting the discharge of crystals and air bubbles from inside the cover body, and effectively suppress the influence of accumulated crystals and air bubbles on the sensor 12.

[0078] Furthermore, according to the method for producing fermentation products of this embodiment, since the diameter of the micropores provided in the lower permeable portion 14a is formed to be 180 μm to 750 μm, it is possible to effectively suppress the intrusion of bubbles of a size that would adversely affect the measurement values ​​of the sensor 12 while allowing the inflow of liquid and crystals into the cover body 14.

[0079] Furthermore, according to the method for producing the fermentation product of this embodiment, the cover body 14 protrudes diagonally downward from the side wall surface 2a of the fermentation tank 2 containing the culture medium L (Figure 3). As a result, air bubbles that rise from below and reach the cover body 14 can easily flow upward along the lower surface of the cover body 14, effectively suppressing their entry into the cover body 14. In addition, air bubbles that do enter the cover body 14 gather at the base end of the cover body 14 located above, thus moving away from the measurement unit 12b of the sensor 12 located near the tip of the cover body 14, thereby reducing any adverse effects on the measurement.

[0080] Although preferred embodiments of the present invention have been described above, various modifications can be made to the embodiments described above. In particular, in the embodiments of the present invention described above, cystine was produced as a fermentation product in a culture medium L containing air bubbles, but the present invention can be applied to the production of any other fermentation product in which air bubbles are present and crystals are formed in the liquid. For example, the present invention can be applied to a fermenter in which amino acids, nucleic acids, or peptides with relatively low solubility and prone to crystallization are produced in a culture medium L containing dissolved fermentation products, a fermentation carbon source, a nitrogen source, a phosphorus source, an oxygen source, and / or a sulfur source.

[0081] Here, examples of fermentation products include amino acids, examples of fermentation carbon sources include sugars, monosaccharides, disaccharides, and polysaccharides, examples of nitrogen sources include ammonia and ammonium sulfate, examples of phosphorus sources include phosphate ions, and examples of sulfur sources include thiosulfate ions. Examples of amino acids, nucleic acids, and peptides that relatively easily precipitate as crystals during fermentation include glutamic acid (Glu), tryptophan (Trp), phenylalanine (Phe), threonine (Thr), tyrosine (Tyr), cysteine ​​(Cys), cystine (Cys2), glutamine (Gln), aspartic acid (Asp), leucine (Leu), isoleucine (Ile), valine (Val), inosine, guanosine, and adenine.

[0082] Furthermore, in the embodiments described above, the concentration of components precipitated in the liquid was measured, but it is also possible to measure the properties of the liquid itself, such as the dielectric constant and conductivity of the liquid, or to measure the bacterial cells in the liquid.

[0083] Furthermore, in the embodiments of the present invention described above, one sensor device 1 was provided in the fermentation tank 2 to measure various properties of the liquid. However, multiple sensor devices 1 can also be provided in a single fermentation tank 2. In this case, different sensor covers can be applied to each sensor device according to the properties that each sensor device measures. For example, one sensor device 1 can measure the properties of precipitated crystals, while another sensor device 1 can measure the properties of components dissolved in the liquid phase. Furthermore, the present invention can also be configured as follows in a preferred configuration. 1. A method for producing a fermentation product, comprising producing a fermentation product by operating a fermentation tank in which air bubbles are mixed in and crystals with an average particle size of 5 μm or more are generated in the liquid, The steps include preparing a fermentation tank and a sensor device for measuring the properties of the liquid in the fermentation tank, The step of adding the liquid to be fermented to the above fermentation tank, The process includes the step of operating the fermentation tank in the above-mentioned fermentation tank, measuring the properties of the liquid in the fermentation tank using the above-mentioned sensor device, and adjusting the conditions of the fermentation operation based on the measurement results. The above sensor device comprises a sensor for measuring the properties of a liquid and a sensor cover body arranged to surround the sensor. At least a portion of the lower surface of the cover body is provided with a lower permeable portion that allows liquid and at least a portion of the crystals in the liquid to pass through, and at least a portion of the upper surface of the cover body is provided with an upper permeable portion that allows liquid and at least a portion of the crystals in the liquid to pass through. A method for producing a fermentation product, characterized in that a large number of micropores for allowing liquid to pass through are formed in the lower permeable portion and the upper permeable portion, and the micropores provided in the upper permeable portion are larger than or equal to the micropores provided in the lower permeable portion. 2. The method for producing the fermentation product according to item 1, wherein the average diameter of the bubbles mixed in the liquid of the fermentation tank is 50 μm or more. 3. The method for producing a fermentation product according to 1 or 2 above, wherein the fermentation tank has a vent pipe for supplying gas into the fermentation tank, and the diameter of the pore at the outlet of the vent pipe is 1 μm or more. 4. The method for producing a fermentation product according to any one of items 1 to 3 above, wherein the fermentation tank has a vent pipe for supplying gas into the fermentation tank, and the volume of gas supplied to the fermentation tank per hour through this vent pipe is no more than twice the volume of the culture medium at the start of fermentation in the fermentation tank. 5. The method for producing a fermentation product according to any one of items 1 to 4, wherein the cover body is formed in a substantially cylindrical shape, and the sensor extends in the axial direction inside it. 6. The method for producing the fermentation product according to item 5, wherein the lower permeable portion is provided across the entire lower semicircular portion of the substantially cylindrical cover body, and the upper permeable portion is provided across the entire upper semicircular portion of the cover body. 7. The method for producing a fermentation product according to any one of items 1 to 6 above, wherein the cover body is formed from a thin metal plate, and the micropores provided in the lower permeable portion and the upper permeable portion are substantially circular holes provided in the thin metal plate. 8. A method for producing a fermentation product according to any one of items 1 to 7, wherein the diameter of the micropores provided in the upper permeable portion is 1 to 5 times the diameter of the micropores provided in the lower permeable portion. 9. The method for producing a fermentation product according to any one of items 1 to 8 above, wherein the diameter of the micropores provided in the lower permeable portion is 540 μm to 750 μm. 10. A method for producing a fermentation product according to any one of items 1 to 9 above, wherein the fermentation product produced by operating the above-mentioned fermentation tank is cysteine, and cystine accumulates in the above-mentioned fermentation tank due to the oxidation of at least a portion of this cysteine. 11. The method for producing a fermentation product according to any one of items 1 to 10, wherein the cover body is provided so as to protrude diagonally downward from the side wall surface of a fermentation tank containing liquid, and the measuring part of the sensor is positioned near the tip of the cover body. 12. A sensor device for measuring the properties of a liquid in a fermentation tank in which air bubbles are present and crystals with an average particle size of 5 μm or more are generated in the liquid, A sensor for measuring the properties of a liquid, The sensor cover body is positioned to surround this sensor, It has, At least a portion of the lower surface of the cover body is provided with a lower permeable portion that allows liquid and at least a portion of the crystals in the liquid to pass through, and at least a portion of the upper surface of the cover body is provided with an upper permeable portion that allows liquid and at least a portion of the crystals in the liquid to pass through. The sensor device is characterized in that the lower permeable portion and the upper permeable portion each have numerous micropores formed therein for allowing liquid to pass through, and the micropores provided in the upper permeable portion are larger than or equal to the micropores provided in the lower permeable portion. [Explanation of Symbols]

[0084] 1. Sensor device 2 Fermentation tanks 2a Side wall 4. Measuring instrument body 6 Stirrer 6a Feather 8. Sparger (ventilation tube) 8a Feeding device 10 Sensor cover 12 sensors 12a Sensor Probe 12b Measurement section 14 Cover body 14a Lower transparent part 14b Upper transparent part 14c Tip surface 16 Flange section 18a Fixing bolts 18b Packing

Claims

1. A apparatus for producing fermentation products, A fermentation tank in which air bubbles are mixed in and crystals with an average particle size of 5 μm or more are generated in the liquid, This fermentation tank is equipped with a vent pipe for supplying gas into the fermentation tank, The fermentation tank has a sensor device for measuring the properties of the liquid inside the tank, The above sensor device is A sensor for measuring the properties of a liquid, The sensor cover body is positioned to surround this sensor, It has, The cover body described above is formed in a roughly cylindrical shape, and the sensor described above extends in the axial direction inside it. At least a portion of the lower surface of the cover body is provided with a lower permeable portion that allows liquid and at least a portion of the crystals in the liquid to pass through, and at least a portion of the upper surface of the cover body is provided with an upper permeable portion that allows liquid and at least a portion of the crystals in the liquid to pass through. The lower and upper permeable sections are each formed with numerous micropores for allowing liquid to pass through, and the micropores in the upper permeable section are larger than or equal to the micropores in the lower permeable section. The diameter of the hole at the outlet of the above-mentioned vent pipe is 1 μm or larger. The apparatus for producing fermentation products is characterized in that the cover body is provided so as to protrude diagonally downward from the side wall surface of the fermentation tank containing the liquid, and the measuring part of the sensor is located near the tip of the cover body.

2. The apparatus for producing fermentation products according to claim 1, wherein the lower permeable portion is provided across the entire lower semicircular portion of the substantially cylindrical cover body, and the upper permeable portion is provided across the entire upper semicircular portion of the cover body.

3. The apparatus for producing fermentation products according to claim 1 or 2, wherein the cover body is formed from a thin metal plate, and the micropores provided in the lower permeable portion and the upper permeable portion are substantially circular holes provided in the thin metal plate.

4. The apparatus for producing fermentation products according to any one of claims 1 to 3, wherein the diameter of the micropores provided in the upper permeable portion is 1 to 5 times the diameter of the micropores provided in the lower permeable portion.

5. The apparatus for producing fermentation products according to any one of Claims 1 to 4, wherein the diameter of the micropores provided in the lower permeable portion is 350 μm to 750 μm.

6. The apparatus for producing fermentation products according to claim 5, wherein the diameter of the micropores provided in the lower permeable portion is 540 μm to 750 μm.

Images