Manufacturing method for fermentation product, and sensor device used for the same

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 in particular to a method for producing a fermentation product by performing fermentation operation in a fermenter in which air bubbles are mixed in and crystals having an average particle size of 5 μm or more are produced in the liquid, and a sensor device used therein. [Background technology]

[0002] In the production of various fermentation products, it is necessary to measure various liquid characteristics such as the electrical conductivity and turbidity of the liquid in the fermenter, 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, a 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 culture solution is sampled at appropriate times to directly analyze the carbon source concentration, or the pH or dissolved oxygen concentration is measured, and a carbon source deficiency state is detected from the changes, thereby measuring the carbon source concentration and controlling 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 manufacturing process and measure the characteristics of the liquid, but it is preferable from the viewpoint of manufacturing efficiency to measure the characteristics of the liquid in-line without taking out the liquid from the manufacturing process. However, when bubbles are mixed in the liquid to be measured or when crystals are formed in the liquid, it may be difficult to measure the characteristics of the liquid in-line. For example, in a culture solution undergoing aeration culture, bubbles of oxygen or air supplied, or bubbles of carbon dioxide gas, which is a metabolic product of the microorganisms themselves during culture, are mixed in, and these bubbles may cause noise to be mixed into the measured values ​​or increase measurement errors.

[0004] Japanese Patent No. 4420168 (Patent Document 2) describes a turbidity sensor. This turbidity sensor has a stainless steel hollow semi-cylindrical member, the lower part of which is provided with an inlet for the test liquid and a swing valve that opens and closes automatically, and the upper part is provided with a hole for removing bubbles. Furthermore, a liquid contact photometer of a laser turbidity meter is disposed at the tip position inside the hollow semi-cylinder. When measuring with this turbidity sensor, first, the swing valve is opened to replace the test liquid inside the hollow semi-cylinder. Next, the swing valve is closed, and the bubbles in the hollow semi-cylinder are discharged from the hole for removing bubbles. The turbidity measurement is performed after waiting for the detected turbidity to stabilize. In this way, the invention described in Patent Document 2 reduces the influence of bubbles in the test liquid. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 3074781 [Patent Document 2] Patent No. 4420168 Summary of the Invention [Problem to be solved by the invention]

[0006] However, in the turbidity sensor described in Patent Document 2, it is necessary to wait for the detection value to stabilize after closing the swing valve, and it is difficult to perform detection in real time. In addition, when the turbidity sensor is applied to a liquid in which crystals are generated, the crystals may accumulate on the moving parts such as the swing valve, which may cause a malfunction. Furthermore, the turbidity sensor described in Patent Document 2 requires a swing valve that is opened and closed by remote control, which makes the structure complicated, and there is a problem that maintenance for stable operation over a long period of time is also troublesome.

[0007] On the other hand, when the sensor is applied to a liquid in which crystals are formed, it is necessary not only to suppress the influence of the bubbles, but also to analyze the amount of precipitated solids simultaneously with the liquid phase when the concentration of the fermentation product in the liquid phase exceeds the solubility and precipitates. If a sensor cover is provided on the sensor to suppress the influence of bubbles, crystals will accumulate near the sensor and inside the sensor cover, making it difficult to accurately measure the concentration of the product. For this reason, it is necessary to devise a way to make the crystal concentration in the fermentation tank equal to the crystal concentration around the sensor, for example by appropriately discharging the crystals that have precipitated inside the sensor cover, so that the crystals do not accumulate.

[0008] Therefore, the present invention aims to provide a method for producing a fermentation product and a sensor device used therein, which has a simple structure, suppresses the effect of air bubbles mixed in the liquid on the sensor measurement results, and prevents crystals generated in the liquid from accumulating near the sensor or inside the sensor cover, measures the characteristics of the liquid and solids in a fermentation tank, and allows fermentation operations to be performed based on the results. [Means for solving the problem]

[0009] In order to solve the above-mentioned problems, the present invention provides a method for producing a fermentation product by performing a fermentation operation on a fermentation tank in which air bubbles are mixed and crystals with an average particle size of 5 μm or more are generated in the liquid, the method comprising the steps of preparing a fermentation tank and a sensor device for measuring the characteristics of the liquid in the fermentation tank, pouring the liquid to be fermented into the fermentation tank, and performing a fermentation operation on the fermentation tank while measuring the characteristics of the liquid in the fermentation tank with the sensor device and adjusting the conditions of the fermentation operation based on the measurement results. The sensor device has a sensor for measuring the characteristics of the liquid and a cover body for the sensor arranged to surround the sensor, and at least a part of the lower surface of the cover body is provided with a lower permeable part that allows at least a part of the liquid and 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 part that allows at least a part of the liquid and the crystals in the liquid to pass through, and the lower permeable part and the upper permeable part are each formed with a large number of fine holes for passing the liquid, and the fine holes provided in the upper permeable part are larger than the fine holes provided in the lower permeable part.

[0010] According to the present invention thus configured, the sensor device for measuring the characteristics of the liquid in the fermenter has a cover body arranged to surround the sensor. The cover body is provided with a lower transparent part and an upper transparent part that allow at least a part of the liquid and the crystals in the liquid to pass through, so that the liquid to be measured can constantly flow in and out of the cover body. As a result, the liquid in the cover body is constantly replaced, and the sensor arranged in the cover body can continuously measure the characteristics of the liquid in real time. In addition, since the lower transparent part and the upper transparent part of the cover body allow at least a part of the crystals in the liquid to pass through, the crystals generated in the liquid are unlikely to accumulate on the cover body, and the fermentation operation can be continued for a long time without performing maintenance such as cleaning the cover body. In addition, since the micropores provided in the upper transparent part are larger than the micropores provided in the lower transparent part, air bubbles floating up from below the cover body are unlikely to pass through the micropores in the lower transparent part, and the intrusion of air bubbles into the cover body can be effectively suppressed. On the other hand, since the micropores in the upper transmission part are formed to be larger than the micropores in the lower transmission part, air bubbles that have entered the cover body tend to rise up inside the cover body and be discharged through the upper transmission part. As a result, it is possible to prevent air bubbles that have entered the cover body from remaining inside the cover body and adversely affecting the measurement values ​​of the sensor.

[0011] In the present invention, the average diameter of the air bubbles mixed in the liquid in the fermenter is preferably 50 μm or more. According to the present invention thus configured, the average diameter of bubbles mixed in the liquid in the fermenter is 50 μm or more, so that the cover body 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, the sensor can obtain stable measurement values. In this specification, the average diameter of bubbles is the mean value of square-weighted chord length obtained by measurement using focused beam reflectance measurement method (FBRM), which corresponds to the so-called volume-based average value.

[0012] In the present invention, the fermenter preferably has an aeration pipe for feeding gas into the fermenter, and the hole diameter of the outlet of this aeration pipe is 1 μm or more. According to the present invention configured in this manner, the hole diameter of the outlet of the vent pipe that sends gas into the fermenter is 1 μm or more, so the average diameter of the air bubbles mixed into the liquid in the fermenter becomes large. Therefore, the cover body can suppress the intrusion of air bubbles while allowing crystals with an average particle diameter of 5 μm or more generated in the liquid to pass through. As a result, the sensor can obtain stable measurement values.

[0013] In the present invention, the fermenter preferably has an aeration pipe for supplying gas into the fermenter, and the volume of gas supplied into the fermenter per hour through this aeration pipe is not more than twice the volume of the medium at the start of fermentation in the fermenter. According to the present invention configured as described above, the volume of gas fed into the fermentation tank through the vent pipe per hour is equal to or less than twice the volume of the medium at the start of fermentation, so that the gas can be dissolved in the liquid without excessively breaking down the gas bubbles fed into the fermentation tank, which makes it easy to prevent the gas bubbles from entering the cover body.

[0014] In the present invention, the cover body is preferably formed into a substantially cylindrical shape, with the sensor extending in the axial direction inside the cover body. According to the present invention configured as described above, since the cover body is formed in a substantially cylindrical shape, air bubbles that rise from the underside of the cover body tend to flow upward along the lower surface of the cover body, which further prevents air bubbles from entering the cover body. Also, since the cover body is formed in a substantially cylindrical shape, air bubbles that have entered the cover body and rise up are collected at the highest part of the cover body, making it difficult for them to come into contact with the sensor. This makes it possible to minimize adverse effects on measurement even if air bubbles enter the cover body.

[0015] In the present invention, the lower transmitting portion is preferably provided over the entire surface of a lower semicircular portion of the substantially cylindrical cover body, and the upper transmitting portion is preferably provided over the entire surface of an upper semicircular portion of the cover body. According to the present invention configured in this way, since the lower semicircular portion and the upper semicircular portion are provided with the lower transparent portion and the upper transparent portion, respectively, the area of ​​the cover body through which the liquid and crystals are transmitted can be made extremely large. As a result, crystals that have entered the cover body can be easily discharged to the outside, and the retention of crystals within the cover body can be suppressed.

[0016] In the present invention, the cover body is preferably formed from a thin metal plate, and the fine holes provided in the lower and upper transparent portions are generally circular holes provided in the thin metal plate. According to the present invention configured in this manner, the fine holes in the lower and upper transmitting parts are formed by holes in a thin metal plate, so crystals are less likely to adhere to and accumulate in the lower and upper transmitting parts compared to when the lower and upper transmitting parts are formed from a mesh material formed by weaving wires, improving the maintainability of the sensor cover. Also, by forming the fine holes in the lower and upper transmitting parts by holes in a thin metal plate, it is possible to configure a cover main body that is less likely to break and has higher durability than a mesh material.

[0017] In the present invention, the diameter of the micropores provided in the upper transmission portion is preferably 1 to 5 times the diameter of the micropores provided in the lower transmission portion. In the present invention thus configured, by setting the diameter of the micropores in the upper transparent portion to 1 to 5 times the diameter of the micropores in the lower transparent portion, it is possible to achieve an appropriate balance between preventing air bubbles from entering the cover body and expelling any air bubbles that have entered the cover body, thereby effectively suppressing the effect of air bubbles on the sensor.

[0018] In the present invention, the diameter of the micropores provided in the lower transmission portion is preferably 540 μm to 750 μm. In the present invention configured in this manner, the diameter of the micropores in the lower transparent portion is set to 540 μm to 750 μm, thereby allowing the inflow of liquid and crystals into the cover body while effectively suppressing the intrusion of air bubbles of a size that could adversely affect the sensor measurement values.

[0019] In the present invention, the fermentation product produced by fermentation operation in a fermenter is preferably cysteine, and cystine accumulates in the fermenter as a result of at least a portion of this cysteine ​​being oxidized. In the present invention thus configured, cysteine ​​is produced as a fermentation product in the fermenter, and at least a portion of this cysteine ​​is oxidized to produce cystine. Therefore, when the diameter of the micropores provided in the lower transmission section is set to 540 μm to 750 μm, the intrusion of air bubbles is effectively suppressed while allowing cysteine ​​and cystine crystals in the liquid to flow in and out of the cover body, and the concentration of cystine can be accurately detected by the sensor.

[0020] In the present invention, the cover body is preferably 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 disposed near the tip of the cover body. In the present invention thus configured, the cover body protrudes obliquely downward from the side wall surface of the fermentation tank containing the liquid, so that air bubbles that rise from below and reach the cover body tend to flow upward along the lower side surface of the cover body, effectively preventing them from entering the cover body. Furthermore, air bubbles that have entered the cover body tend to gather at the base end of the cover body located at the top, so that they move away from the measuring unit of the sensor located near the tip end of the cover body, reducing adverse effects on the measurement.

[0021] The present invention also provides a sensor device for measuring the characteristics of a liquid in a fermentation tank in which air bubbles are mixed and crystals with an average particle size of 5 μm or more are generated in the liquid, the sensor device comprising: a sensor for measuring the characteristics 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 transparent portion which allows at least a part of the liquid and 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 transparent portion which allows at least a part of the liquid and the crystals in the liquid to pass through, the lower transparent portion and the upper transparent portion each having a large number of fine holes for allowing the liquid to pass through, and the fine holes provided in the upper transparent portion are larger than or equal to the fine holes provided in the lower transparent portion. Effect of the Invention

[0022] The method for producing a fermentation product of the present invention and the sensor device used therein have a simple structure and can suppress the effect of air bubbles mixed in the liquid on the sensor measurement results, while preventing crystals formed in the liquid from accumulating near the sensor or inside the sensor cover, thereby measuring the characteristics of the liquid and solids in the fermentation tank and performing fermentation operations based on the results. [Brief description of the drawings]

[0023] [Figure 1] FIG. 2 is a cross-sectional view showing an example in which a sensor device used to carry out a method for producing a fermentation product according to an embodiment of the present invention is applied to a fermenter. [Diagram 2] FIG. 2 is a perspective view showing the appearance of a cover body for a sensor provided in the sensor device according to the embodiment of the present invention. [Diagram 3] FIG. 2 is an enlarged cross-sectional view showing a state in which a sensor device according to an embodiment of the present invention is attached to a side wall surface of a fermenter. [Figure 4] 5 is an enlarged view showing an example of a micropore provided on a surface of a cover body in the sensor device according to the embodiment of the present invention. FIG. [Diagram 5] 10A to 10C are diagrams illustrating the function of a sensor cover in a sensor device according to an embodiment of the present invention. [Figure 6] 1 is a flow chart showing the steps of a method for producing a fermentation product according to an embodiment of the present invention. [Figure 7] FIG. 13 is a diagram showing an example of measurement performed without using a sensor cover. [Figure 8] FIG. 13 shows an example of a measurement using a sensor device with an appropriate sensor cover. [Figure 9] FIG. 13 is a diagram showing an example of a case where a measurement is performed using a sensor cover whose pores are too small. [Figure 10] 1A and 1B are diagrams showing the state of various sensor covers after use. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] Next, preferred embodiments of the present invention will be described with reference to the accompanying drawings. Fig. 1 is a cross-sectional view showing an example in which a sensor device used for carrying out a method for producing a fermentation product according to an embodiment of the present invention is applied to a fermenter. Fig. 2 is a perspective view showing the appearance of a cover body for a sensor provided in the sensor device according to an embodiment of the present invention. Fig. 3 is an enlarged cross-sectional view showing a state in which the sensor device according to an embodiment of the present invention is attached to a side wall surface of a fermenter.

[0025] As shown in FIG. 1, a sensor device 1 according to an embodiment of the present invention is provided on a side wall surface 2a of a fermenter 2, which is a container that contains a liquid, and is configured to measure the concentration of amino acids in a culture solution L, which is a liquid contained in the fermenter 2, in-line. Furthermore, a sensor is disposed inside the sensor device 1, and a signal acquired by this sensor is transmitted to a measurement device main body 4. In this embodiment, the fermenter 2 is generally cylindrical, and an agitator 6 for agitating the culture solution is provided along its central axis. The agitator 6 is provided with a plurality of blades 6a for agitating the culture solution L, and by rotating these blades 6a, the culture solution L in the fermenter 2 is agitated so as to become homogenous.

[0026] In this embodiment, in order to perform aeration culture in the fermenter 2, a sparger 8, which is an aeration pipe, is provided at the bottom of the fermenter 2, and oxygen or air is introduced into the fermenter 2 from a supply device 8a through the sparger 8. Therefore, fine bubbles of the supplied oxygen or air, and fine bubbles of carbon dioxide gas generated by the cultured microorganisms are mixed into the culture liquid L. In this embodiment, the hole diameter of the outlet of the sparger 8 for discharging gas is about 6 mm, and thus bubbles with an average diameter of about 250 μm are mixed into the culture liquid in the fermenter 2. Preferably, the hole diameter of the hole for discharging gas provided in the sparger 8 or the like is set to about 5 μm to about 36 μm, and bubbles with an average diameter of about 150 μm to about 350 μm are mixed into the culture liquid in the fermenter 2. Alternatively, a Fine Air Diffuser (FAD) can be used as an aeration pipe for mixing bubbles into the culture liquid. The FAD has many pores with diameters of about 1 μm to about 20 μm, which allows air bubbles with an average diameter of about 50 μm to about 250 μm to be mixed into the culture solution.

[0027] Next, the configuration of the sensor device 1 according to the embodiment of the present invention will be described with reference to FIGS. As shown in FIG. 3, the sensor device 1 includes 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 that is provided at the base end of the cover body 14 and fixed to the side wall surface 2 a of the fermenter 2 . The cover body 14 is formed of a thin plate made of stainless steel and is configured to have a substantially cylindrical shape with a closed tip, and is disposed so as to surround the sensor 12. As will be described later, the cover body 14 has a large number of fine holes on its entire surface, and the liquid and at least some of the crystals in the fermenter 2 can flow into the cover body 14 through these fine holes. The cover body can be configured to have any shape other than a cylinder, such as a rectangular parallelepiped. The cover body can also be formed of metals other than stainless steel or resins such as polytetrafluoroethylene, and is preferably formed of a material that is not easily damaged by the flow of liquid caused by stirring.

[0029] The flange portion 16 is a stainless steel disk, and the cover body 14 is fixed to the center of the flange portion 16 by welding to form an integrated unit. The cover body 14 is attached perpendicularly 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 disposed between the flange portion 16 and the side wall surface 2a, ensuring watertightness between the flange portion 16 and the side wall surface 2a. Furthermore, as shown in FIG. 3, the portion on the outside of the side wall surface 2a where 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 fermenter 2, the cover body 14 protrudes obliquely downward toward the inside from the side wall surface of the vessel. The mounting angle of the cover body 14 is preferably set at an angle that can prevent air bubbles from entering the cover body 14 and prevent liquid from pooling near the cover body 14 and causing the proliferation of bacteria, and can also be set at an angle close to horizontal depending on the nature of the liquid. In this embodiment, the central axis of the cover body 14 is inclined at about 16 degrees with respect to the horizontal axis.

[0030] In this embodiment, a transmission reflection type near infrared spectroscopic sensor (NIR sensor) is used as the sensor 12, and near infrared analysis is used to measure the concentration of amino acids in the culture solution L. However, the sensor cover 10 in this embodiment can be applied to various sensors other than the NIR sensor, such as spectroscopic sensors that use ultraviolet or visible light, other optical sensors, sensors that use focused beam reflectance measurement (FBRM) for measuring crystal particle size, and electromagnetic sensors for measuring dielectric constant and conductivity, and can be combined with these sensors to configure a sensor device.

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

[0032] Next, with new reference to Figs. 4 and 5, the configuration of the cover body 14 provided in the sensor cover 10 according to the embodiment of the present invention will be described in detail. Fig. 4 is an enlarged view showing an example of a micropore provided on the surface of the cover body 14. Fig. 5 is a schematic view showing 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 a large number of micropores formed on its entire surface, allowing at least a part of the surrounding liquid and crystals to flow into the inside of the cover body 14. Here, in the sensor device 1 of this embodiment, it is preferable to set the size of each micropore provided on the upper surface of the cover body 14 to be equal to or larger than 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 transparent portion 14a that allows liquid to pass through, and the upper surface is provided with an upper transparent portion 14b that allows liquid to pass through, and the micropores provided in the upper transparent portion 14b are formed to be the same as or larger than the micropores provided in the lower transparent portion 14a.

[0034] 2, the lower transmissive portion 14a is formed on the entire surface of a lower semicircular portion corresponding to the lower semicircle of the cover body 14 having a circular cross section, and the upper transmissive portion 14b is formed on the entire surface of an upper semicircular portion corresponding to the upper semicircle of the cover body 14. In addition, a large number of fine holes identical to those in the lower transmissive portion 14a are formed on the entire surface of the tip surface 14c of the cover body 14.

[0035] In this specification, the "lower surface" of the cover body 14 means the surface on which light hits when light is projected vertically from below onto the sensor cover 10 installed in the usage state, and the "upper surface" means the surface on which light hits when light is projected vertically from above. In this embodiment, a large number of 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, and may be formed on only a part of the surface. In this embodiment, micropores are also formed on the tip surface 14c of the cover body 14, but the tip surface 14c does not need to be provided with micropores.

[0036] Next, as shown in FIG. 4, the lower transmission part 14a and the upper transmission part 14b have approximately circular microholes arranged in a staggered pattern. That is, the microholes are arranged so that the lines connecting the centers of three adjacent microholes form an equilateral triangle. In this embodiment, the lower transmission part 14a and the upper transmission part 14b are formed by forming a large number of microholes by etching a thin plate made of stainless steel. As an example, in this embodiment, the lower transmission part 14a is formed by arranging circular holes with a diameter D of about 750 μm at a pitch P of about 1070 μm (the length of the side of an equilateral triangle connecting the centers of the circles). In this embodiment, the upper transmission part 14b is also formed by arranging circular holes with a diameter D of about 750 μm at a pitch P of about 1070 μm.

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

[0038] As an example, when circular holes with a diameter D of about 540 μm are arranged with a pitch P of about 770 μm, the opening rate is about 44.5%, which is roughly equivalent to a 30# mesh. When circular holes with a diameter D of about 350 μm are arranged with a pitch P of about 630 μm, the opening rate is about 28%, which is roughly equivalent to a 40# mesh. When circular holes with a diameter D of about 250 μm are arranged with a pitch P of about 360 μm, the opening rate is about 43.6%, which is roughly equivalent to a 60# mesh. When circular holes with a diameter D of about 180 μm are arranged with a pitch P of about 320 μm, the opening rate is about 28.7%, which is roughly equivalent to a 80# mesh. When circular holes with a diameter D of approximately 150 μm are arranged with a pitch P of approximately 250 μm, the opening rate is approximately 32.5%, which is roughly equivalent to a 100# mesh, and when circular holes with a diameter D of approximately 100 μm are arranged with a pitch P of approximately 210 μm, the opening rate is approximately 20.5%, which is roughly equivalent to a 150# mesh.

[0039] In this embodiment, the lower transmitting portion 14a and the upper transmitting portion 14b are made of a thin plate with many fine holes formed therein, but the lower transmitting portion 14a and the upper transmitting portion 14b can also be made of a net-like material formed by combining thin wires by weaving, knitting, or the like. In this case, the "fine holes" are formed as spaces between the wires that make up the net-like material, and the "size of the fine holes" means the distance between adjacent wires. Preferably, the diameter of the fine holes provided in the lower transmitting portion 14a is set to about 180 μm to about 750 μm. More preferably, the diameter of the fine holes provided in the lower transmitting portion 14a is set to about 250 μm to about 750 μm. Even more preferably, the diameter of the fine holes provided in the lower transmitting portion 14a is set to about 350 μm to about 750 μm. Even more preferably, the diameter of the fine holes provided in the lower transmitting portion 14a is set to about 540 μm to about 750 μm. That is, the diameter of the micropores provided in the lower transmission part 14a is preferably set to a size that suppresses the intrusion of air bubbles in the culture solution L and allows the passage of at least some of the crystals in the culture solution L. Furthermore, the lower transmission part 14a and the upper transmission part 14b, which have a large number of micropores formed in a thin plate, are less susceptible to crystals adhering and accumulating, and the maintainability of the sensor cover can be improved.

[0040] In addition, in order to facilitate the discharge of air bubbles trapped in the cover body, it is preferable that the micropores in the upper transmitting portion 14b are formed to be larger than or equal to the micropores in the lower transmitting portion. However, it is preferable that the diameter of the micropores in the upper transmitting portion 14b is set to a diameter that can sufficiently prevent air bubbles from flowing through the upper transmitting portion 14b due to the downward flow of liquid. Preferably, the diameter of the micropores in the upper transmitting portion 14b is set to about 1 to about 5 times the diameter of the micropores in the lower transmitting portion 14a. This allows an appropriate balance between the prevention of air bubbles from entering the cover body 14 and the discharge of air bubbles that have entered the cover body 14.

[0041] Next, the function of the sensor cover will be explained typically with reference to FIG. First, when measuring the characteristics of a liquid containing air bubbles, it has been known that the effect of the air bubbles is reduced by covering the sensor with a mesh strainer. However, as shown in FIG. 5(a), when crystals are mixed in the culture liquid L, if the size of the micropores in the cover body 14 (lower transmission part 14a, upper transmission part 14b) is set too fine to prevent the air bubbles from entering, neither the air bubbles B nor the crystals C can enter the inside of the strainer. In such a case, the components of the crystals cannot be measured by the sensor, and accurate measurement cannot be performed.

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

[0043] More preferably, as shown in FIG. 5(c), fine holes having a small diameter are formed in the lower transmission part 14a of the cover body 14, and fine holes larger than the lower transmission part 14a are formed in the upper transmission part 14b. By forming the cover body 14 in this manner, large bubbles floating up from below are prevented from entering the cover body 14. At least a part of the crystals in the culture liquid L enters the cover body 14 through the lower transmission part 14a and is detected by the sensor. In addition, as shown in FIG. 5(c), by providing the cover body 14 so as to protrude obliquely downward from the side wall surface 2a of the fermenter 2, the bubbles prevented from entering by the cover body 14 tend to move obliquely upward along the lower surface of the cover body 14, and most of the bubbles B move upward while easily bypassing the sensor cover 10.

[0044] On the other hand, even if the air bubbles approach from below, small ones will penetrate into the cover body 14 through the lower transmission part 14a. However, by forming fine holes with a large diameter in the upper transmission part 14b, small air bubbles that penetrate through the lower transmission part 14a will rise up inside the cover body 14 and be easily discharged outside the cover body 14 through the upper transmission part 14b. This makes it possible to prevent the invading air bubbles from remaining in the cover body 14 for a long time and growing into large bubbles.

[0045] Also, although not all air bubbles approach sensor cover 10 from below, because air bubbles are always buoyant due to the liquid, a large proportion of air bubbles approach sensor cover 10 from below, and the intrusion of these air bubbles is significantly suppressed by lower transmission part 14a. Furthermore, upper transmission part 14b also effectively prevents the intrusion of some air bubbles approaching sensor cover 10 from above, sides, etc. due to the flow of liquid caused by stirring in the fermentation tank, more effectively than when the top of the cover is made completely open. Also, by forming the micropores in upper transmission part 14b large, crystals C can more easily infiltrate into sensor cover 10, and the crystalline components can be detected more accurately.

[0046] Furthermore, by providing the cover body 14 so as to protrude diagonally downward, air bubbles that have entered the cover body 14 move upward toward the base end of the cover body 14. Meanwhile, since the measuring part 12b of the sensor probe 12a disposed within the cover body 14 is disposed in the vicinity of the tip end of the cover body 14, air bubbles within the cover body 14 are moved away from the measuring part 12b of the sensor 12. This makes it possible to further reduce the effect of air bubbles that have entered the cover body 14 on the measurement. Due to these actions, the sensor cover 10 of this embodiment effectively reduces the effect of air bubbles on measurement.

[0047] Next, a method for producing a fermentation product using the sensor device 1 according to an embodiment of the present invention will be described with reference to FIGS. Fig. 6 is a flow chart showing the steps of a method for producing a fermentation product according to an embodiment of the present invention. Fig. 7 is a diagram showing an example of a case where a measurement is performed without using a sensor cover 10. Fig. 8 is a diagram showing an example of a measurement by a sensor device 1 using an appropriate sensor cover 10. Fig. 9 is a diagram showing an example of a case where a measurement is performed using a sensor cover 10 whose pores are too fine. Furthermore, Fig. 10 is a diagram showing the state of various sensor covers 10 after use.

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

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

[0050] As the carbon source, sugars such as glucose, fructose, sucrose, molasses and starch hydrolysates, and organic acids such as fumaric acid, citric acid and succinic acid can be used. As the nitrogen source, inorganic ammonium salts such as ammonium sulfate, ammonium chloride, and ammonium phosphate, organic nitrogen such as that from soybean hydrolysate, ammonia gas, and aqueous ammonia can be used. Examples of sulfur sources include inorganic sulfur compounds such as sulfates, sulfites, sulfides, hyposulfites, and thiosulfates. As organic trace nutrients, it is desirable to include an appropriate amount of required substances such as vitamin B1, yeast extract, etc. In addition to these, small amounts of potassium phosphate, magnesium sulfate, iron ions, manganese ions, etc. may be added as necessary.

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

[0052] Furthermore, the conditions of the fermentation operation are adjusted based on the measurement results by the sensor device 1. In this embodiment, cystine is produced by the fermentation operation, and as the amount of cystine dissolved in the culture solution L increases, it precipitates and cystine crystals are produced. The characteristics of the culture solution L during the fermentation operation are measured at any time by the sensor device 1. In this embodiment, the characteristics of the culture solution L measured by the sensor device 1 include the cystine concentration [g / L], as well as the sugar concentration [g / L] (RS), the ammonia nitrogen concentration (AN), and each of the SO3 concentrations [g / L], and the turbidity (OD) of the culture solution L.

[0053] Furthermore, the conditions of the fermentation operation are adjusted based on the characteristics of the culture solution L measured by the sensor device 1. The conditions of the fermentation operation that are adjusted can include the temperature of the culture solution L, the pH of the culture solution L, the amount of aeration fed through the sparger 8, the amount of sugar solution added, medium components such as phosphorus added, etc. The adjustment of the fermentation operation conditions based on the measured characteristics of the culture solution L is performed as needed during the fermentation operation.

[0054] Next, the measurement of cystine concentration by the sensor device 1 will be described. As described above, the sensor device 1 is provided with the sensor 12 (FIG. 3). In this embodiment, the sensor 12 is an NIR sensor, and light received by the sensor probe 12a is guided to the measurement device main body 4 (FIG. 1) via an optical fiber. The measurement device main body 4 acquires the NIR spectrum of the guided light. By applying a calibration model created in advance to the NIR spectrum obtained for the light from the sensor probe 12a, the concentration of cystine and the like contained in the culture solution L can be estimated. FIGS. 7 to 9 are graphs showing the time-dependent change in the cystine concentration estimated in this manner.

[0055] Fig. 7 shows an example in which the cystine concentration in the culture solution L in the fermenter 2 was measured (estimated) using the sensor 12 without attaching the sensor cover 10. As shown in Fig. 7, in the measurement without using the sensor cover 10, although there is a tendency for the concentration of cystine produced in the fermenter 2 to increase over time, the estimated value varies greatly from measurement to measurement. This is thought to be because air bubbles mixed in the culture solution L affect the light received by the sensor probe 12a, causing the estimated value to vary.

[0056] Fig. 8 shows an example of an estimated value of the concentration of cystine in the culture solution L measured in the example shown in Fig. 7, when the concentration is measured using a sensor device 1 equipped with a sensor cover 10. In the example shown in Fig. 8, a sensor cover 10 having micropores equivalent to 20# formed in each of the lower transmission section 14a and the upper transmission section 14b is used. As shown in Fig. 8, when a sensor cover 10 having micropores equivalent to 20# is used, the estimated cystine concentration shows the same tendency as when a sensor cover 10 is not used.

[0057] In addition, in the example shown in FIG. 8, the fluctuation of the estimated value of the cystine concentration is smaller than that in the example shown in FIG. 7, and the cystine concentration is stably measured. This is thought to be because the sensor cover 10 is provided so as to surround the sensor 12, which suppresses the influence of bubbles mixed in the culture liquid L and stabilizes the measured value. In addition, cystine has a low solubility in the culture liquid L, and most of the cystine produced in the fermenter 2 precipitates and crystallizes. The average particle diameter of this crystallized cystine is 5 μm or more, and it is found that the crystallized cystine is detected even in a state where the sensor cover 10 is attached to the sensor 12. That is, it is found that the lower transmission part 14a and the upper transmission part 14b of the sensor cover 10 pass at least a part of the culture liquid L and the crystals in the culture liquid L.

[0058] FIG. 9 shows an example of the concentration of cystine in the culture solution L measured in the example shown in FIG. 8, using a sensor cover 10 with smaller micropores than those in FIG. 8. In the example shown in FIG. 9, a sensor cover 10 with micropores equivalent to 60# formed in the lower transmission part 14a and the upper transmission part 14b is used. In the example shown in FIG. 9, a stable estimated value of the cystine concentration is obtained immediately after the start of the fermentation operation, as in the example shown in FIG. 8, but the fluctuation of the estimated value increases with the passage of time. Then, as time passes, abnormal values ​​appear in the estimated value, and finally the concentration of cystine cannot be estimated. This is because scaling of cystine crystals occurs on the outside of the sensor cover 10 during the fermentation operation, and the crystals accumulate on the inside of the sensor cover 10.

[0059] That is, for the fermentation operation to produce cystine in the culture solution L in the fermenter 2, the sensor cover 10 having micropores equivalent to 60# is considered to have too fine micropores to allow the crystals precipitated from the liquid phase to be discharged from the cover, resulting in the accumulation and retention of the crystals. In contrast, in the example shown in Fig. 8, there is substantially no accumulation of crystals on the sensor cover 10 even after a long fermentation operation, and it can be said that the sensor cover 10 having micropores equivalent to 20# is appropriate for the fermentation operation to produce cystine.

[0060] 8 and 9, the lower and upper transmission parts 14a and 14b of the sensor cover 10 have the same size of micropores, but the size of the micropores in the upper transmission part 14b can be made larger than that of the lower transmission part 14a. In this case, air bubbles that have entered the sensor cover 10 can be easily discharged through the upper transmission part 14b, so that it is expected that the adverse effect of the air bubbles on the measurement value can be further reduced. For example, the micropores in the upper transmission part 14b of the sensor cover 10 used in the measurement shown in FIG. 8 can be changed to 10# to 15#, which is larger than the micropores in the lower transmission part 14a.

[0061] Next, with reference to FIG. 10, the state of crystal deposition when measurements are performed using various sensor covers 10 will be described. FIG. 10 is a table summarizing the results of experiments conducted on the state of crystal deposition and the stability of the measurement data obtained when various sensor covers 10 were used.

[0062] As shown in Fig. 10, the experiment was conducted under condition (1) when no sensor cover 10 was used, and under conditions (2) to (5) when sensor covers 10 equivalent to 20#, 30#, 40#, and 60# were used. Furthermore, under condition (6), an experiment was also conducted under the condition that the lower transparent portion 14a of the sensor cover 10 was equivalent to 80# and the upper transparent portion 14b was equivalent to 40#. In the experiment, the deposition state of crystals on the sensor 12 and the sensor cover 10 after fermentation operation was performed for a predetermined time under each condition was observed.

[0063] First, as shown in Fig. 10, when the sensor cover 10 of condition (1) was not used, no adhesion of crystals to the sensor 12 (crystal scaling) was observed, but the estimated value of the cystine concentration fluctuated significantly, making it impossible to measure stable data. That is, when the sensor cover 10 was not provided, crystallized cystine could also be measured by the sensor 12, but the estimated value of the cystine concentration was contaminated with large noise due to the influence of air bubbles mixed in the culture solution L, causing large fluctuations (hunting) in the estimated value.

[0064] Next, when the sensor cover 10 equivalent to 20# in condition (2) and 30# in condition (3) was used, neither adhesion of crystals to the outer surfaces of the sensor 12 and the sensor cover 10 nor retention of crystals (crystal accumulation) in the sensor cover 10 was observed. Furthermore, there was no significant fluctuation in the estimated value of the cystine concentration, and stable data could be measured. That is, when the sensor cover 10 was equivalent to 20# or 30#, the size of the micropores was sufficiently larger than the average particle size of the cystine crystals, and the cystine crystals could sufficiently penetrate into the sensor cover 10. Furthermore, the cystine crystals that penetrated into the sensor cover 10 were detected by the sensor 12, and a highly reliable estimated value of the cystine concentration was obtained, and the crystals that penetrated into the sensor cover 10 easily flowed out of the sensor cover 10. On the other hand, most of the air bubbles mixed in the culture solution L were prevented from penetrating into the sensor cover 10, and the adverse effect of the air bubbles on the sensor 12 was suppressed.

[0065] Next, when the sensor cover 10 equivalent to 40# in condition (4) was used, no crystals were found to adhere to the outer surfaces of the sensor 12 and the sensor cover 10, but a small amount of crystals were found to remain inside the sensor cover 10. In addition, during the experiment, the estimated value of the cystine concentration did not fluctuate significantly, and stable data could be measured. However, under these conditions, if the fermentation operation is performed for a longer period of time, the amount of crystals remaining inside the sensor cover 10 may increase, making it difficult to obtain appropriate measurement values. Thus, when the micropores provided in the sensor cover 10 are small, the intrusion of air bubbles into the sensor cover 10 can be more strongly suppressed, which is advantageous for eliminating the adverse effects of air bubbles. On the other hand, when the micropores are small, the cystine crystals that enter the sensor cover 10 and the crystals generated inside the cover are difficult to be discharged outside, and the crystals tend to accumulate inside the sensor cover 10.

[0066] Furthermore, when a sensor cover 10 equivalent to 60# under condition (5) was used, crystals were observed to adhere to the outer surfaces of the sensor 12 and the sensor cover 10, and a large amount of crystals were also observed to remain within the sensor cover 10. In addition, due to the influence of the crystals remaining within the sensor cover 10, it became impossible to obtain appropriate data during the experiment. In this way, when a sensor cover 10 having finer pores than those under condition (4) is used, the effect of suppressing the intrusion of air bubbles becomes stronger, but the amount of cystine crystals remaining within the sensor cover 10 increases significantly. When a large amount of cystine crystals remain within the sensor cover 10 in this way, the cystine concentration within the sensor cover 10 becomes significantly high, making it difficult to accurately measure the cystine concentration of the culture solution L in the fermenter 2.

[0067] Finally, in the condition (6) where the lower transmission part 14a of the sensor cover 10 was set to 80# and the upper transmission part 14b was set to 40#, no crystals were found to adhere to the outer surfaces of the sensor 12 and the sensor cover 10, but a small amount of crystals was found to remain inside the sensor cover 10. In addition, during the experiment, the estimated value of the cystine concentration did not fluctuate significantly, and stable data could be measured. However, under these conditions, if the fermentation operation is performed for a longer period of time, the amount of crystals remaining inside the sensor cover 10 may increase, making it difficult to obtain appropriate measurement values. In addition, under condition (6), although the micropores of the lower transmission part 14a are set to 80#, which is finer than under condition (5), better results were obtained than under condition (5). That is, under condition (6), the micropores of the upper transmission part 14b are larger than those under condition (5), so it is considered that crystals are less likely to remain inside the sensor cover 10. Therefore, by finely adjusting the size of the pores in the sensor cover 10 of 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 transparent portion 14a with fine pores.

[0068] From the results shown in Fig. 10, it was found that sensor covers 10 having micropores equivalent to 20# and 30# are suitable for the fermentation operation to produce cystine in the culture solution L in the fermenter 2. Fig. 10 shows the results when cystine was produced as the fermentation product in the fermenter 2, but when producing other fermentation products in which crystals are produced, it is only necessary to design sensor covers 10 with micropores of an appropriate size according to the average particle size of the produced crystals and the average diameter of the air bubbles mixed in the culture solution L.

[0069] According to the method for producing a fermentation product of the embodiment of the present invention, the sensor device 1 for measuring the characteristics of the culture solution L, which is a liquid in a fermenter 2, has a cover body 14 arranged to surround a sensor 12 (FIG. 3). This cover body 14 is provided with a lower transparent portion 14a and an upper transparent portion 14b that allow the culture solution L and at least a part of the crystals in the culture solution L to pass through, so that the culture solution L to be measured can constantly flow in and out of the cover body 14. As a result, the culture solution L in the cover body 14 is constantly replaced, and the sensor 12 arranged in the cover body 14 can continuously measure the characteristics of the culture solution L containing the crystals in real time.

[0070] In addition, since the lower transmission part 14a and the upper transmission part 14b of the cover body 14 allow at least a part of the crystals in the culture liquid L to pass through, the crystals generated in the culture liquid L are unlikely to accumulate on the cover body 14, and the fermentation operation can be continued for a long time without performing maintenance such as cleaning the cover body 14. In addition, since the micropores provided in the upper transmission part 14b are larger than the micropores provided in the lower transmission part 14a, air bubbles floating up from below the cover body 14 are unlikely to pass through the micropores of the lower transmission part 14a, and the intrusion of air bubbles into the cover body 14 can be effectively suppressed. On the other hand, since the micropores of the upper transmission part 14b are formed to be larger than the micropores of the lower transmission part 14a, air bubbles that have invaded the cover body 14 rise up within the cover body 14 and are easily discharged through the upper transmission part 14b. As a result, it is possible to suppress the air bubbles that have invaded the cover body 14 from remaining in the cover body 14 and adversely affecting the measured value of the sensor 12.

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

[0072] Furthermore, according to the method for producing a fermentation product of this embodiment, the hole diameter of the outlet of the vent pipe that sends gas into the fermenter 2 is 6 mm, so that the average diameter of the air bubbles mixed into the culture liquid L in the fermenter 2 becomes large. Therefore, the cover body 14 can suppress the intrusion of air bubbles while allowing crystals with an average particle diameter of 5 μm or more generated in the culture liquid L to pass through. As a result, a stable measurement value can be obtained by the sensor 12.

[0073] Furthermore, according to the method for producing a fermentation product of this embodiment, the volume of air, which is a gas, fed into the fermenter 2 per hour through the sparger 8, which is an aeration pipe, is 0.1 to 1.2 times the volume of the medium at the start of fermentation, so that the air can be dissolved in the culture solution L without excessively breaking down the air bubbles fed into the fermenter 2. As a result, the intrusion of air bubbles into the cover body 14 can be easily suppressed.

[0074] Furthermore, according to the method for producing a fermentation product of this embodiment, the cover body 14 is formed in a substantially cylindrical shape (FIG. 2), so that air bubbles that rise from the underside of the cover body 14 tend to flow upward along the lower surface of the cover body 14, further preventing air bubbles from entering the cover body 14. Also, because the cover body 14 is formed in a substantially cylindrical shape, air bubbles that have entered the cover body 14 and rise to the surface are collected at the highest part within the cover body 14, making it difficult for them to come into contact with the sensor 12. As a result, even if air bubbles enter the cover body 14, adverse effects on the measurement can be minimized.

[0075] Furthermore, according to the method for producing a fermentation product of this embodiment, the lower permeable portion 14a and the upper permeable portion 14b are provided on the entire surfaces of the lower semicircular portion and the upper semicircular portion, respectively, so that it is possible to greatly increase the portion of the cover body 14 through which the culture solution L and the crystals permeate. As a result, the crystals that have entered the cover body 14 are easily discharged to the outside, and the retention of the crystals within the cover body 14 can be suppressed.

[0076] Furthermore, according to the method for producing a fermentation product of this embodiment, the micropores of the lower transparent portion 14a and the upper transparent portion 14b are formed by holes provided in a thin metal plate (FIG. 4), so compared to when the lower transparent portion 14a and the upper transparent portion 14b are formed from a net-like material formed by weaving wires, crystals are less likely to adhere to and accumulate on the lower transparent portion 14a and the upper transparent portion 14b, improving the maintainability of the sensor cover 10. Also, by forming the micropores of the lower transparent portion 14a and the upper transparent portion 14b by holes provided in a thin metal plate, it is possible to configure a cover body 14 that is more resistant to breakage and has higher durability than a net-like material.

[0077] Furthermore, in the method for producing a fermentation product of this embodiment, when the diameter of the micropores in the upper transparent section 14b is set larger than the diameter of the micropores in the lower transparent section 14a, the intrusion of air bubbles into the cover body 14 can be effectively suppressed while promoting the discharge of crystals and air bubbles from within the cover body, and the effect of the retained crystals and air bubbles on the sensor 12 can be effectively suppressed.

[0078] Furthermore, according to the method for producing a fermentation product of this embodiment, the diameter of the micropores provided in the lower transparent portion 14a is formed to be 180 μm to 750 μm, so that the intrusion of air bubbles of a size that is likely to adversely affect the measurement value of the sensor 12 can be effectively suppressed while allowing the inflow of liquid and crystals into the cover body 14.

[0079] Furthermore, according to the method for producing a fermentation product of this embodiment, the cover body 14 protrudes obliquely downward from the side wall surface 2a of the fermenter 2 containing the culture liquid L (FIG. 3), so that air bubbles that rise from below and reach the cover body 14 tend to flow upward along the lower side surface of the cover body 14, effectively preventing the air bubbles from entering the cover body 14. Furthermore, air bubbles that enter the cover body 14 gather at the base end of the cover body 14 located above, and therefore move away from the measuring unit 12b of the sensor 12 arranged near the tip end of the cover body 14, reducing adverse effects on the measurement.

[0080] Although the preferred embodiment of the present invention has been described above, various modifications can be made to the above-mentioned embodiment. In particular, in the above-mentioned embodiment of the present invention, cystine is produced as a fermentation product in the culture solution L containing air bubbles, but the present invention can be applied to the production of any other fermentation product in which air bubbles are mixed and crystals are produced in the liquid. For example, the present invention can be applied to a fermenter in which an amino acid, nucleic acid, or peptide with a relatively low solubility and prone to crystallization is produced in the culture solution L containing dissolved fermentation products, fermentation carbon sources, nitrogen sources, phosphorus sources, oxygen sources, and / or sulfur sources.

[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 are relatively likely to crystallize 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, adenine, and the like.

[0082] Furthermore, in the above-described embodiment, the concentration of components that precipitate in the liquid is measured, but it is also possible to measure the characteristics of the liquid itself, such as the dielectric constant or conductivity of the liquid, or to measure the bacterial cells in the liquid.

[0083] Furthermore, in the above-described embodiment of the present invention, one sensor device 1 is provided in the fermenter 2 to measure various properties of the liquid, but multiple sensor devices 1 can also be provided in one fermenter 2. In this case, different sensor covers can be applied to each sensor device depending on the property that each sensor device measures. For example, one sensor device 1 can measure the property of precipitated crystals, and another sensor device 1 can measure the property of a component dissolved in the liquid phase. [Explanation of symbols]

[0084] 1 Sensor device 2 Fermentation tank 2a Side wall 4 Measuring instrument body 6 Stirrer 6a Feather 8 Sparger (vent pipe) 8a Feeding device 10 Sensor cover 12 Sensors 12a Sensor probe 12b Measurement section 14 Cover body 14a Lower transparent part 14b Upper transparent section 14c Tip surface 16 Flange section 18a Fixing bolt 18b Gasket

Claims

1. A method for producing a fermentation product, comprising: performing fermentation operation on a fermenter in which air bubbles are mixed and crystals having an average particle size of 5 μm or more are produced in the liquid; and producing a fermentation product, Providing a fermenter and a sensor device for measuring a property of a liquid in the fermenter; introducing the liquid to be fermented into the fermenter; and a step of measuring the characteristics of the liquid in the fermenter by the sensor device while performing a fermentation operation in the fermenter, and adjusting the conditions of the fermentation operation based on the measurement results. The sensor device includes a sensor for measuring a property of a liquid, and a cover body for the sensor arranged to surround the sensor, A lower transparent portion that allows at least a portion of the liquid and the crystals in the liquid to pass through is provided on at least a portion of the lower surface of the cover body, and an upper transparent portion that allows at least a portion of the liquid and the crystals in the liquid to pass through is provided on at least a portion of the upper surface of the cover body, A method for producing a fermentation product, characterized in that a large number of micropores for passing a liquid are formed in the lower transmission section and the upper transmission section, and the micropores provided in the upper transmission section are larger than or equal to the micropores provided in the lower transmission section.

2. 2. The method for producing a fermentation product according to claim 1, wherein the average diameter of bubbles mixed in the liquid in the fermenter is 50 μm or more.

3. 3. The method for producing a fermentation product according to claim 1, wherein the fermenter has an aeration pipe for feeding gas into the fermenter, and the hole diameter of the outlet of the aeration pipe is 1 μm or more.

4. 4. The method for producing a fermentation product according to claim 1, wherein the fermentation tank has an aeration pipe for supplying gas into the fermentation tank, and the volume of gas supplied into the fermentation tank per hour through the aeration pipe is not more than twice the volume of the medium at the start of fermentation in the fermentation tank.

5. 5. The method for producing a fermentation product according to claim 1, wherein the cover body is formed in a substantially cylindrical shape, and the sensor extends in the axial direction inside the cover body.

6. 6. The method for producing a fermentation product according to claim 5, wherein the lower transmission portion is provided over the entire surface of the lower semicircular portion of the substantially cylindrical cover body, and the upper transmission portion is provided over the entire surface of the upper semicircular portion of the cover body.

7. The method for producing a fermentation product according to any one of claims 1 to 6, wherein the cover body is formed from a thin metal plate, and the micropores provided in the lower transmission section and the upper transmission section are approximately circular holes provided in the thin metal plate.

8. 8. The method for producing a fermentation product according to claim 1, wherein the diameter of the micropores provided in the upper transmission section is 1 to 5 times the diameter of the micropores provided in the lower transmission section.

9. The method for producing a fermentation product according to any one of claims 1 to 8, wherein the diameter of the micropores provided in the lower transmission section is 540 µm to 750 µm.

10. 10. A method for producing a fermentation product according to claim 1, wherein the fermentation product produced by fermenting the fermenter is cysteine, and cystine is accumulated in the fermenter by oxidizing at least a portion of the cysteine.

11. A method for producing a fermentation product according to any one of claims 1 to 10, wherein the cover body is arranged to protrude diagonally downward from the side wall surface of a fermentation tank containing a liquid, and the measuring portion of the sensor is positioned near the tip of the cover body.

12. A sensor device for measuring the characteristics of a liquid in a fermentation tank in which air bubbles are mixed and crystals with an average particle size of 5 μm or more are generated in the liquid, A sensor for measuring a property of the liquid; a sensor cover body arranged to surround the sensor; having A lower transparent portion that allows at least a portion of the liquid and the crystals in the liquid to pass through is provided on at least a portion of the lower surface of the cover body, and an upper transparent portion that allows at least a portion of the liquid and the crystals in the liquid to pass through is provided on at least a portion of the upper surface of the cover body, A sensor device characterized in that a large number of micropores for allowing liquid to pass therethrough are formed in the lower transmission portion and the upper transmission portion, and the micropores provided in the upper transmission portion are larger than or equal to the micropores provided in the lower transmission portion.

Images