Culture system, culture device, and control method for culture system

Abstract

To identify changes in the culture conditions of cultured cells during culturing.SOLUTION: A culture system (100) includes: a culture tank (11) capable of housing cultured cells; an odor measurement device (30) that measures an odor inside the culture tank (11) housing the cultured cells; and an information processing device (50) that estimates a culture condition of the cultured cells on the basis of a measurement signal output from the odor measurement device (30).SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a culture system, a culture apparatus, and a method for controlling a culture system.

Background Art

[0002] In recent years, devices for estimating the state of a target based on the odor in a specific target have been developed. For example, Patent Document 1 describes a specific device for identifying the source and cause of an unknown odor in a steel mill or the like, using coke odor and tar odor, which are odors collected from assumed odor sources in a steel mill, as reference odors.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] When culturing cells that produce a product, the culture is stopped at an optimal timing that can obtain as much product as possible. Conventionally, the timing to stop the culture can be determined in advance by collecting cells during the previously performed culture over time and measuring the change in the number of cells and the change in the amount of the produced product. Also, whether the timing at which the culture was stopped was appropriate can be verified by the analysis performed for each culture after the culture is completed. However, since the growth rate of the cells during the culture and the amount of the produced product can vary even under the same culture conditions, the timing determined in advance is not always the optimal timing. In order to stop the culture at the optimal timing, it was necessary for the user to recognize the change in the culture state of the currently cultured cells.

[0005] One aspect of the present invention aims to recognize the change in the culture state of cultured cells during the culture.

Means for Solving the Problem

[0006] In order to solve the above problems, the culture system according to the present invention includes a culture tank capable of accommodating cultured cells, an odor measurement unit that measures the odor inside the culture tank accommodating the cultured cells, and an information processing device that outputs an estimation result obtained by estimating the culture state of the cultured cells based on a measurement signal output from the odor measurement unit.

[0007] In order to solve the above problems, the culture device according to the present invention includes a culture tank capable of accommodating cultured cells and an odor measurement device that measures the odor inside the culture tank.

[0008] In order to solve the above problems, the control method of the culture system according to the present invention includes a measurement signal acquisition step of acquiring a measurement signal output from an odor measurement unit that measures the odor inside a culture tank accommodating cultured cells, and an estimation step of outputting an estimation result obtained by estimating the culture state of the cultured cells based on the measurement signal.

Advantages of the Invention

[0009] According to one aspect of the present invention, it is possible to recognize changes in the culture state of cultured cells during culture.

Brief Description of the Drawings

[0010]

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Mode for Carrying Out the Invention

[0011] 〔Embodiment 1〕 An embodiment of the present invention will be described below, but the present invention is not limited thereto. Also, unless otherwise specified in this specification, "A to B" representing a numerical range is intended to mean "A or more and B or less".

[0012] (Culture System 100) First, the outline of a culture system 100 according to an embodiment of the present invention will be described with reference to FIG. 1. FIG. 1 is a schematic diagram showing an example of the configuration of a culture system 100 according to an embodiment of the present invention. As shown in FIG. 1, the culture system 100 includes a culture device 10, an odor measurement device (odor measurement unit) 30, and an information processing device 50.

[0013] The culture device 10 includes a culture tank 11, a discharge unit 12, and a stirring unit 13. The culture tank 11 can accommodate cultured cells. The cultured cells are, for example, Escherichia coli. The culture tank 11 is not particularly limited and any-shaped container can be used. Also, the culture tank 11 may be able to accommodate at least one of a liquid medium and a solid medium for culturing the cultured cells. The culture tank 11 does not have airtightness so that aerobic culture can be carried out. Inside the culture tank 11, a gas such as air or oxygen is supplied from a gas supply device (not shown).

[0014] The culture tank 11 is provided with a stirring unit 13 for stirring the fluid in the culture tank 11. The stirring unit 13 is not particularly limited, and the stirring unit 13 includes, for example, a propeller type with a propeller formed at the tip, an anchor type with the tip portion having an anchor shape, or a stirring rod such as a straight rod type with the tip portion extending straight. Note that the stirring unit 13 may not be provided in the culture tank 11. The culture tank 11 is provided with a discharge unit 12 for discharging the gas inside the culture tank 11 containing the cultured cells to the outside of the culture tank 11. The discharge unit 12 is, for example, a pipe.

[0015] In the culture system 100, the measurement of the odor inside the culture tank 11 is performed by offline measurement. The user collects the gas inside the culture tank 11 by the gas collection unit 20. The gas collection unit 20 has a sampling port 21 and can collect gas from the sampling port 21. The user can collect the gas discharged from the discharge unit 12 or the gas inside the discharge unit 12 by the gas collection unit 20, for example, by connecting the sampling port 21 of the gas collection unit 20 to the discharge unit 12 via a hose, a tube, or a pipe. The gas collection unit 20 includes, for example, a sampling bag or a container made of SUS (stainless steel). Note that the material of the sampling bag is not particularly limited, and it may be a sampling bag made of, for example, polyvinylidene fluoride, polyvinyl fluoride, aluminum, fluororesin, or polyester.

[0016] The user connects the gas sampling unit 20 that has sampled the gas inside the culture tank 11 and the atmosphere storage unit 25 that stores the refresh gas to the odor measurement device 30. The refresh gas stored in the atmosphere storage unit 25 is the background atmosphere under odor measurement. The refresh gas stored in the atmosphere storage unit 25 contains, for example, nitrogen or air. The atmosphere storage unit 25 includes, for example, a sampling bag or a SUS container. Note that the material of the sampling bag is not particularly limited, and it may be a sampling bag made of, for example, polyvinylidene fluoride, polyvinyl fluoride, aluminum, fluororesin, or polyester.

[0017] The odor measurement device 30 measures the odor inside the culture tank 11 that contains the cultured cells. The odor measurement device 30 can output a measurement signal based on the odor inside the culture tank 11 during the culturing of the cultured cells. The detailed configuration of the odor measurement device 30 will be described later.

[0018] The gas supply unit 40 supplies the gas inside the gas sampling unit 20 and the refresh gas inside the atmosphere storage unit 25 connected to the odor measurement device 30 to the odor measurement device 30 at a constant flow rate. The gas supply unit 40 includes, for example, a pump, a fan, or a compressor. By driving the gas supply unit 40, the gas inside the gas sampling unit 20 and the atmosphere storage unit 25 is supplied to the odor measurement device 30. Thereby, the odor measurement device 30 can measure the odor inside the culture tank 11.

[0019] The information processing device 50 is a terminal device such as a personal computer used by a user who uses the culture system 100. Based on the measurement signal from the odor measurement device 30, it estimates the culture state of the cultured cells being cultured in the culture tank 11 and outputs the estimation result. Further, the information processing device 50 can output an estimation result obtained by estimating the culture state of the currently cultured cells by using, as learning data, information on the culture state collected in the past based on the feature amount based on the measurement signal, the information on the culture conditions, and the elapsed time since the start of the culture. The information on the culture conditions may be information based on a sensor signal obtained from a device other than the odor measurement device 30 described later (for example, a temperature sensor or a dissolved oxygen (DO) sensor). The information on the culture state collected in the past includes, for example, the culture state of the cultured cells collected in the past, the feature amount based on the measurement signal from the odor measurement device 30, the information on the culture conditions, and the elapsed time since the start of the culture. The information processing device 50 estimates, for example, a culture state correlated with the expression level of a protein produced by Escherichia coli. Further, the information processing device 50 may further estimate the end time of the culture, the change time of the culture conditions, etc. based on the estimated culture state.

[0020] The information processing device 50 may perform the estimation based on the feature amount, the elapsed time, and the information on the culture conditions of the currently cultured cells. Here, "currently" means the timing when the odor measurement device 30 measures the odor in the culture tank 11 being cultured, which is the estimation target of the information processing device 50. Further, the information processing device 50 may be provided with a display on which the output estimation result is displayed.

[0021] In the culture system 100, as shown in FIG. 1, the odor measurement device 30 and the information processing device 50 may be connected via a wide - area communication network 70. Further, the odor measurement device 30 and the information processing device 50 may be connected by a local area network connection without passing through a provider or the like, LTE communication, or the like. The wide - area communication network 70 is not particularly limited and may be the Internet, a telephone line network, a mobile communication network, a CATV communication network, a satellite communication network, or the like.

[0022] Note that the information processing apparatus 50 may be realized as a cloud server connected to the wide - area communication network 70. In this case, the information processing apparatus 50 may acquire the measurement signal of the odor measuring apparatus 30 from the terminal device used by the user who uses the culture system 100 via the wide - area communication network 70, and transmit the output estimation result to the terminal device used by the user. Also, in this case, the terminal device used by the user and the odor measuring apparatus 30 may be connected by a local area network connection, LTE communication, etc. without going through a provider or the like.

[0023] Note that the "cultured cells" are not limited to Escherichia coli. The "cultured cells" may be selected from at least any one of microbial cells, animal cells, and plant cells. The microbial cells may include bacteria, fungi (e.g., Bacillus subtilis, lactic acid bacteria, etc.), archaea, and protists, etc. Examples of the microbial cells for aerobic culture include lactic acid bacteria, Bifidobacterium, etc. Examples of the microbial cells for anaerobic culture include acetic acid bacteria, Bacillus subtilis, etc. In the case of specific microbial cells such as yeast, Escherichia coli, etc., anaerobic culture or aerobic culture can be selected according to the purpose of culture. The animal cells may include cells of vertebrates such as mammals including humans, fish, reptiles, amphibians, and birds, as well as cells of invertebrates such as insects. Also, the "cultured cells" may be any cells such as cells established as cultured cells (e.g., cultured meat), induced pluripotent stem cells (iPS cells), non - established normal cells obtained from biological tissues, transformed cells obtained by genetic engineering techniques, and pluripotent stem cells.

[0024] Also, the "culture state" is not limited to indicating the expression level of the protein produced by the cultured cells. The "culture state" may be anything that indicates the expression level of a product that is an arbitrary substance that can be produced by the cultured cells. Such products include, for example, amino acids, alcohols, biodegradable plastics, etc., but are not limited thereto. Also, the product may include, for example, the cultured cells themselves that have proliferated by cell division. That is, the "culture state" may be information indicating the number of cultured cells.

[0025] The number of the odor measurement devices 30 included in the culture system 100 according to an embodiment of the present invention is not particularly limited, and may be one or more, three or more, five or more, or ten or more. Further, the odor measurement devices 30 may be installed in different culture tanks, or some or all of them may be installed in the same culture tank.

[0026] In the culture system 100, the connection between the odor measurement device 30 and the information processing device 50 may be a wired connection or a wireless connection. The information processing device 50 and the odor measurement device 30 may be connected via a wide area communication network 70. The information processing device 50 may be configured on a server capable of communicating with the odor measurement device 30. In this case, the culture system 100 may include a device such as a terminal device that enables the user to grasp the estimation result output by the information processing device 50.

[0027] In the culture system 100, the odor measurement device 30 includes a plurality of sensor elements 31. The plurality of sensor elements 31 may detect different odor substances from each other or may be the same. The measurement signal is output from each of the plurality of odor sensor elements 31. Hereinafter, details of the odor sensor element 31, the odor measurement device 30 to which the odor sensor element 31 is applied, and the culture system 100 including the odor measurement device 30 and the information processing device 50 will be described.

[0028] (Odor measurement device 30) Hereinafter, the outline and effects of the odor measurement device 30 to which the odor sensor element 31 is applied will be described with reference to FIG. 2. FIG. 2 is a functional block diagram showing an example of the odor measurement device 30 to which the odor sensor element 31 is applied. The odor measurement device 30 includes an odor sensor element 31 that detects an odor substance, a power supply 32 (power source), a clock 33 (timer), and a control unit 34 and a communication unit 35. As described above, the odor measurement device 30 may be connected to the information processing device 50.

[0029] The odor measuring device 30 is arranged, for example, at a position where the gas in the culture tank can reach. Also, a filter may be provided in the path until the gas in the culture tank reaches the position where the odor measuring device 30 is arranged. The filter includes, for example, a filter of activated carbon, a membrane filter, and a mechanical filter such as a HEPA filter (High Efficiency Particulate Air Filter). The position where the odor measuring device 30 is arranged may be, for example, the wall surface inside the culture tank where the gas in the culture tank can reach. Also, if necessary, a fan or the like capable of supplying air containing odor substances toward the odor sensor element 31 of the odor measuring device 30 may be installed.

[0030] The power supply 32 is a power supply for supplying power to the odor sensor element 31. The constant voltage power supply 32 supplies a constant current (for example, a direct current of 1 mA) to the odor sensor element 31 via a lead wire. The voltage value supplied by the constant voltage power supply 32 is 0.5 V to 10 V, for example, 2.5 V or 5.0 V.

[0031] The clock 33 measures time. The clock 33 transmits the measured time to the control unit 34. The clock 33 may be a clock whose time is set by the user, or may be a radio clock.

[0032] The control unit 34 comprehensively controls each part of the odor measuring device. Also, the control unit 34 outputs the odor detected by the odor sensor element 31 as a measurement signal. The control unit 34 may output a measurement signal of the odor according to the time measured by the clock 33. Also, the control unit 34 may output information indicating the time when the odor was detected together with the measurement signal.

[0033] The communication unit 35 transmits the measurement signal output by the control unit 34. The communication unit 35 transmits the measurement signal to the wide area communication network 70, and the transmitted measurement signal is acquired by the information processing device 50.

[0034] The odor measuring device 30 may further include a housing, although this is not an essential component. The housing is a container capable of enclosing air containing an odor substance. When the housing is provided, the odor sensor element 31 is installed inside the housing.

[0035] The odor measuring device 30 outputs a measurement signal indicating a change over time in the electrical conductivity of the odor sensor element 31 before and after an odor substance is adsorbed to the odor sensor element 31. Thereby, it is possible to detect and identify various odor substances.

[0036] <Odor sensor element 31> FIG. 3 is a top view showing an example of the configuration of the odor sensor element 31. The odor sensor element 31 includes an odor substance receiving layer 315 containing the above-described resin composition, a first metal wiring 313A, and a second metal wiring 313B. In the following, when the first metal wiring 313A and the second metal wiring 313B are not distinguished, they may be referred to as the metal wiring 313.

[0037] The first metal wiring 313A and the second metal wiring 313B are each metal wirings that function as electrodes for measuring a change in the electrical conductivity of the odor substance receiving layer 315 (i.e., the resin composition). That is, the first metal wiring 313A and the second metal wiring 313B are spaced apart from each other, and the odor substance receiving layer 315 is in contact with at least a part of the first metal wiring and at least a part of the second metal wiring. In one example, the first metal wiring 313A and the second metal wiring 313B are metal wirings that are not in direct contact with each other, and as shown in FIG. 3, they may be metal wirings that are substantially parallel to each other. In the following description, when the metal wiring 313 functions as an electrode, it may also be referred to as the "electrode 313".

[0038] As shown in FIG. 3, the metal wiring 313 including the first metal wiring 313A and the second metal wiring 313B may be disposed on the substrate 311. The substrate 311 can be a substrate such as glass epoxy commonly used in electronic circuits. The substrate 311 is not limited to glass epoxy, and may be a paper phenol, glass composite, polyimide, PET, glass ceramic, alumina, or aluminum substrate. The metal wiring 313 can be a metal wiring such as copper or gold. The thickness of each of the first metal wiring 313A and the second metal wiring 313B as viewed from a direction perpendicular to the surface of the substrate is preferably, for example, 10 μm to 2 mm, and more preferably 10 μm to 1 mm. The height, i.e., the thickness, of each of the first metal wiring 313A and the second metal wiring 313B as viewed from a direction parallel to the surface of the substrate is preferably 1 μm to 100 μm, and more preferably 10 μm to 50 μm. The interval between the first metal wiring 313A and the second metal wiring 313B is preferably 1 μm to 3 mm, and more preferably 1 μm to 1.5 mm. The length of the metal wiring 313 is preferably 100 μm to 50 mm, and more preferably 500 μm to 30 mm.

[0039] The odorant receiving layer 315 may be in contact with at least a part of the first metal wiring 313A and at least a part of the second metal wiring 313B. The odorant receiving layer 315 may be arranged, for example, as shown in FIG. 3, so as to fill the region sandwiched between the first metal wiring 313A and the second metal wiring 313B.

[0040] When the electrical conductivity of the odorant receiving layer 315 (i.e., the electrical conductivity of the odor sensor element 31) is low, it is desirable that the interval between the first metal wiring 313A and the second metal wiring 313B is a predetermined distance (for example, 500 μm) or less.

[0041] The odorant receptor layer may contain a resin composition. The resin composition contains a resin and may further contain one or more selected from a surfactant and a filler (for example, a conductive carbon material). In the present specification, the "odorant receptor layer" means a layer that adsorbs an odorant to be identified. The odorant receptor layer 315 is formed from the above-described resin composition. The odorant receptor layer 315 may be provided as a part of the odor sensor element 31. The electrical resistance value of this odorant receptor layer 315 changes according to the adsorption of the odorant or the like. That is, the odor sensor element 31 is an odor detection device including such an odorant receptor layer 315, and the odor measurement method of the odor sensor element 31 may be a chemiresistor type. Further, the odor sensor element 31 is not limited to the above-described chemiresistor type odor sensor element, and may include one or more odor sensor elements used for known odor sensors or the like.

[0042] When the odor sensor element 31 is of the chemiresistor type containing a resin composition, the temporal change in electrical conductivity is different when odorant A is adsorbed and when an odorant B different from odorant A is adsorbed. Therefore, it is possible to detect and identify various odorants. In the odor measurement device 30 described later, a plurality of odor sensor elements 31 including a substrate 311 provided with a configuration (metal wiring 313 and odorant receptor layer 315) for detecting an odorant are arranged. A plurality of sets each including a plurality of odorant receptor layers 315 are arranged on each substrate 311. Each of the plurality of odor sensor elements 31 may include a constant voltage power supply and a voltmeter. In the odor measurement device 30, a configuration (metal wiring 313 and odorant receptor layer 315) for detecting an odorant may be arranged on each substrate 311. Alternatively, in the odor measurement device 30, a plurality of sets of a configuration (metal wiring 313 and odorant receptor layer 315) for detecting an odorant may be arranged on one substrate 311. In the latter case, a constant voltage power supply and a voltmeter are connected to each of the sets provided on the substrate 311.

[0043] The resin compositions contained in the odorant-receiving layers 315 of the plurality of odor sensors 31 included in the odor measuring device 30 may be the same or different from each other. When the odorant-receiving layers 315 included in the plurality of odor sensors 31 have the same composition, the plurality of odorant-receiving layers 315 can each detect the same odorant. Also, when the plurality of odor sensors 31 each include an odorant-receiving layer 315 with a different composition, each of the plurality of odorant-receiving layers 315 responds differently to the odorant. Thus, by providing a plurality of sets of configurations for detecting odorants, the identification accuracy of odorants in the odor measuring device 30 can be improved.

[0044] When various odorants are adsorbed on the odor sensor 31 in the above-described odor measuring device 30, the temporal change in the electrical conductivity of the odor sensor 31 can be output for each odorant. By applying this odor measuring device 30, it is possible to compare the temporal change in the electrical conductivity of the odor sensor 31 when the odorant A is adsorbed on the odor sensor 31 with the temporal change in the electrical conductivity of the odor sensor 31 when the odorant B is adsorbed on the odor sensor 31. Based on such a comparison result, it is possible to realize an information processing device 50 that can estimate the yield of the product in the current culture described later from the odorant adsorbed on the odor sensor 31.

[0045] (Information processing device 50) Hereinafter, the outline and effects of the information processing apparatus 50 will be described. The information processing apparatus 50 is an apparatus that estimates the culture state of cultured cells in the culture tank 11 based on the measurement signal output from the above-described odor measurement apparatus 30. Since the information processing apparatus 50 uses a learned model obtained by machine learning, it can perform highly accurate determination of odor substances. Note that the information processing apparatus 50 may perform estimation based on sensor signals obtained from apparatuses other than the odor measurement apparatus 30. An apparatus other than the odor measurement apparatus 30 is an apparatus such as a sensor capable of detecting information related to the culture conditions of cultured cells. For example, it may be a carbon dioxide sensor (e.g., a CO2 concentration meter), a temperature sensor, a pH sensor (e.g., a pH meter), a dissolved oxygen (DO) sensor (e.g., a Bio-Engineer dissolved oxygen sensor (DO electrode) OX_Series, manufactured by Marubishi Corporation), a turbidity sensor (UV-1700, manufactured by Shimadzu Corporation), a humidity sensor, or a VOC (Volatile Organic Compounds) sensor. The information processing apparatus 50 may use the signal acquired from the odor measurement apparatus 30 and the signal from an apparatus other than the above-described odor measurement apparatus 30.

[0046] FIG. 4 is a functional block diagram showing an example of the configuration of the information processing apparatus 50. The information processing apparatus 50 includes a control unit 5 that comprehensively controls each part of the information processing apparatus 50, a storage unit 6 that stores various data used by the information processing apparatus 50, and an input unit 54 that inputs information related to the culture conditions of cultured cells, but is not limited to this configuration. For example, the storage unit 6 may be an apparatus externally attached to the information processing apparatus 50. Also, as described above, the information processing apparatus 50 may be connected to the wide-area communication network 70.

[0047] The input unit 54 is for receiving various input operations from the user and may be, for example, a keyboard, a mouse, a touch panel, or the like.

[0048] <Control Unit 5> First, the control unit 5 will be described. The control unit 5 includes an acquisition unit 51, an extraction unit 52, and an estimation unit 53. Also, for a part of the blocks included in the control unit 5, the function thereof may be provided to another device capable of communicating with the information processing device 50, and the block may be omitted from the control unit 5.

[0049] The acquisition unit 51 acquires the measurement signal output from the odor measurement device 30. Specifically, the acquisition unit 51 acquires the detection signals from each of the plurality of odor sensor elements 31. The acquisition unit 51 may acquire the measurement signal in real time, or may acquire the measurement signal at a predetermined time interval (for example, at an interval of 0.1 seconds). Preferably, the acquisition unit 51 acquires the measurement signal every first time. The acquisition unit 51 may store the acquired measurement signal data in the storage unit 6. In addition to the measurement signal, the acquisition unit 51 may further acquire information indicating the elapsed time from the odor measurement device 30.

[0050] The first time may be, for example, 1 minute, 5 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, or more, but is not particularly limited.

[0051] The extraction unit 52 extracts a feature amount indicating the characteristics of the target odor from the measurement signal acquired by the acquisition unit 51. The feature amount extracted by the extraction unit 52 may be, for example, a value related to at least either the signal intensity and the change over time of the measurement signals output from each of the plurality of odor sensor elements 31 provided in the odor measurement device 30.

[0052] More specifically, the feature amount may be the signal intensity ratio of the measurement signals output by the plurality of odor sensor elements 31, or may be the difference in the signal intensity of the measurement signals output by other odor sensor elements 31 based on the signal intensity of the measurement signal output by a specific odor sensor element 31. Also, the feature amount may be a waveform indicating the change over time of the measurement signal or a change pattern over time of the measurement signal.

[0053] The feature amount may be, for example, the difference or ratio between the signal intensity of the measurement signal output by the odor measuring device 30 based on a reference gas such as compressed air or dried nitrogen and the signal intensity of the measurement signal obtained by measuring the odor of the cultured cells during culture. Alternatively, the feature amount may be the difference or ratio between the signal intensity of the measurement signal obtained by measuring the odor of the cultured cells during culture and a preset threshold value. Alternatively, the feature amount may be the difference or ratio between the signal intensity of the measurement signal obtained by measuring the odor of the cultured cells during culture and the signal intensity of the measurement signal at a time point before the timing to be estimated.

[0054] The estimation unit 53 inputs data indicating the feature amount based on the measurement signal, information on the culture conditions, and the elapsed time from the start of culturing of the cultured cells to the learned model 61, and estimates the culture state of the cultured cells currently being cultured. The estimation unit 53 estimates, for example, the yield of the product in the current culture. The measurement signal may be the measurement signal data stored in the storage unit 6. The estimation unit 53 may perform the estimation of the yield of the product, for example, by classification. The information processing device 50 may store information indicating the time (date and time) when the culturing of the cultured cells was started. In this case, the estimation unit 53 may specify the elapsed time from the start of culturing of the cultured cells to the present based on the information and the current time. Alternatively, the estimation unit 53 may acquire information indicating the elapsed time from the odor measuring device 30.

[0055] As the estimation of the yield of the product, the estimation unit 53 may estimate, for example, the yield of the product obtained by culturing, such as the weight of the current product with respect to the weight of the cultured cells at the start of culture, the weight of the current product with respect to the weight of the product during past culture, etc. Further, the estimation unit 53 may estimate a value indicating the number of cultured cells in the culture medium, for example, a numerical value indicating the amount of cells in the current culture medium when the amount of cells at the start of culture is set to 1. The estimation unit 53 may further estimate the progress of the culturing of the cultured cells based on the estimation results at a plurality of timings and the elapsed time. The estimation unit 53 may store the estimation result data in the storage unit 6.

[0056] Further, the information processing apparatus 50 may further include a determination unit that determines whether the culture state is good or bad based on the estimation result by the estimation unit 53. The determination unit acquires the estimation result indicating the culture state of the cultured cells by the estimation unit 53, and determines whether the culture state of the cultured cells is good or bad based on a preset threshold value. For example, when the value indicating the culture state of the cultured cells estimated by the estimation unit 53 is within the range of the threshold value, the determination unit determines that the culture state of the cultured cells is good, and when the value is outside the range of the threshold value, the determination unit determines that the culture state of the cultured cells is bad. When the information processing apparatus 50 includes a determination unit, the determination result by the determination unit may be output together with the estimation result by the estimation unit 53.

[0057] <Storage unit 6> Next, the storage unit 6 will be described. The storage unit 6 may store a learned model 61. Further, measurement signal data and estimation result data may be stored as necessary. The storage unit 6 may store culture condition data of the cultured cells and data indicating the time when the cultured cells were started to be cultured.

[0058] The measurement signal data is data of a measurement signal that is output from the odor measurement device 30 and acquired by the acquisition unit 51. Information such as the measured time, the measured location, the identification number of the odor measurement device 30, and the type of the measurement signal pattern may be labeled in the measurement signal data.

[0059] The learned model 61 is learned by machine learning using teacher data. The teacher data includes the following explanatory variables and target variables. · The explanatory variables include a combination of information on culture conditions, the elapsed time since the start of culture, and feature amounts based on the measurement signals output from the odor measurement device 30 that measured the odor in the culture tank when culturing the cultured cells using the culture tank in the past. · The target variables include yield information indicating the yield of the product produced from the cultured cells at each of the elapsed times since the start of culture of the cultured cells.

[0060] Examples of the information regarding the culture conditions include information such as the culture conditions of the cultured cells, for example, the type of the cultured cells, the culture amount, and the environment of the culture tank in which the cultured cells are cultured. The environment of the culture tank may include the temperature and humidity inside the culture tank, and the purity of the air, etc. By including such information as explanatory variables in the learned model 61, it becomes possible to more accurately estimate the yield of the current product based on the information input from the input unit 54.

[0061] The learned model 61 may be generated using a known machine learning algorithm. Examples of the machine learning algorithms that can be used as the generation method of the learned model 61 include, for example, the k-nearest neighbor method, logistic regression, support vector machine, random forest, and neural network, etc.

[0062] The estimation result data is the result of estimating the yield of the product in the current culture output from the estimation unit 53. The estimation result data may be labeled with the same information as the measurement signal data that is the basis of the estimation.

[0063] (Processing performed by the culture system 100) The outline of the information processing method according to an embodiment of the present invention will be described with reference to FIG. 5. FIG. 5 is a flowchart showing an example of a control method by the culture system 100.

[0064] In step S1, the odor measuring device 30 measures the odor in the culture tank 11 in which the cultured cells are being cultured and outputs it as a measurement signal. At this time, the odor measuring device 30 may output the result of measuring the odor to the information processing device 50 in real time, or may output it every first hour described above.

[0065] In step S2, acquisition unit 51 acquires the measurement signal output from the odor measuring device 30 (measurement signal acquisition step). Acquisition unit 51 may acquire the measurement signal in real time, or may acquire the measurement signal at a predetermined time interval (for example, at an interval of 0.1 seconds). Acquisition unit 51 may store the acquired measurement signal in storage unit 6.

[0066] In step S3, extraction unit 52 extracts a feature quantity from the measurement signal. Extraction unit 52 may extract, for example, as the feature quantity, the ratio or difference of the measurement signals, or a waveform indicating the change over time of the measurement signal, or a change pattern over time of the measurement signal.

[0067] In step S4, estimation unit 53 inputs the feature quantity extracted in step S3 into the learned model 61, and estimates the culture state of the cultured cells currently being cultured (estimation step). At this time, the learned model 61 is obtained by machine learning using teacher data. The explanatory variables and objective variables included in the teacher data are as described above. Estimation unit 53 may store the output estimation result in storage unit 6.

[0068] In step S5, estimation unit 53 outputs the estimation result estimated in step S4. The estimation result output by estimation unit 53 is displayed on, for example, a display.

[0069] When culturing cultured cells in a culture medium, it is difficult to directly and time-dependently measure the yield of the product produced by the cultured cells. Therefore, the yield of the product can be quantified for the first time only after the culture is completed by electrophoresis, assay, or the like. As another method, there is a method of measuring the amount of cells in the culture medium by measuring the turbidity of the culture tank during the culture of the cultured cells, and estimating the yield of the product based on this. However, since the culture medium during the culture of the cultured cells is stirred, it has been difficult to accurately measure the turbidity due to bubbles generated on the liquid surface or the like.

[0070] There is also a method of detecting the gas generated during culturing by gas chromatography or the like. However, since the target gas differs depending on the type of cultured cells to be cultured, and since precise analysis by gas chromatography is required, it has been difficult to grasp the yield of the product over time.

[0071] According to the configuration of the culture system 100, the culture state of the cultured cells during culturing is estimated based on the smell inside the culture tank 11. Thereby, the user can recognize the change in the culture state of the cultured cells during culturing.

[0072] Further, when using the culture system 100, the estimation unit 53 inputs, into the learned model, information regarding the culture conditions of the current cell culture, the elapsed time since the start of culturing, and a feature amount based on the measurement signal obtained by measuring the smell inside the culture vessel during culturing, and estimates the culture state of the cultured cells during the current culturing. Here, the learned model is machine-learned using teacher data including an explanatory variable including a combination of the culture conditions, the elapsed time since the start of culturing, and the feature amount based on the measurement signal when culturing cells in the past, and an objective variable including yield information indicating the yield of the product produced from the cells at the elapsed time. The objective variable may include information indicating the number of cultured cells.

[0073] According to the culture system 100, the culture state of the cells can be accurately estimated, and the user can grasp the culture state of the cultured cells in real time. Thereby, it is possible to immediately notify the user of the timing at which the optimal amount of many products can be obtained from the culture state of the cultured cells during the current culturing. In the present specification, the "optimal amount" means the amount that is optimal in the production of an arbitrary product when using the product. That is, the optimal amount of the product may vary depending on the type of the product and the product to be produced using the product. That is, the "timing at which the optimal amount of the product can be obtained" may be the timing at which the yield of the product becomes the highest, or may be the timing at which the previously determined yield of the product can be obtained.

[0074] 〔Embodiment 2〕 Another embodiment of the present invention will be described below with reference to FIG. 6. FIG. 6 is a schematic diagram showing an example of the configuration of a culture system 100A according to an embodiment of the present invention. For convenience of explanation, members having the same functions as those described in the above embodiment are denoted by the same reference numerals, and the description thereof will not be repeated. The culture system 100A of Embodiment 2 is different from the culture system 100 of Embodiment 1 in that the odor measuring device 30 is provided at the discharge part 12A of the culture device 10A.

[0075] As shown in FIG. 6, the culture device 10A of the culture system 100A includes a culture tank 11, a discharge part 12A, a stirring part 13, an odor measuring device 30, a gas supply part 40, a rectifying device 41, and a discharge device 42. The discharge part 12A discharges the gas inside the culture tank 11 containing the cultured cells to the outside of the culture tank 11. The discharge part 12A has a first discharge part 121, a gas storage part 122, and a second discharge part 123.

[0076] The first discharge part 121 is a flow path for supplying the gas inside the culture tank 11 to the gas storage part 122. The first discharge part 121 is composed of, for example, a pipe for discharging the gas inside the culture tank 11 to the outside of the culture tank 11 and a flexible tube. The tube is extended from the pipe and connected to the gas storage part 122.

[0077] The gas storage part 122 can store the gas inside the culture tank 11 supplied to the odor measuring device 30 via the first discharge part 121. The gas storage part 122 includes, for example, a laminar bag, a sampling bag, or a SUS container. The material of the sampling bag is not particularly limited, and may be, for example, a sampling bag made of polyvinylidene fluoride, polyvinyl fluoride, aluminum, fluororesin, or polyester. According to the configuration provided with the gas storage part 122, the gas in the culture tank 11 can be stored in the gas storage part 122. Thereby, the gas inside the culture tank 11 can be stably supplied to the odor measuring device 30.

[0078] A rectifying device 41 may be provided in the first discharge section 121. The rectifying device 41 is a device capable of supplying the gas inside the culture tank 11 to the gas storage section 122 at a constant flow rate. As an example of the rectifying device 41, a gas flow controller can be mentioned. By the rectifying device 41, the gas inside the culture tank 11 can be supplied to the gas storage section 122 at an arbitrary flow rate via the first discharge section 121.

[0079] Note that the culture device 10A may not be provided with the rectifying device 41. For example, instead of the rectifying device 41, a pump may be provided in the culture device 10A, and the gas inside the culture tank 11 may be supplied to the gas storage section 122 by the pump.

[0080] A discharge device 42 may be provided in the gas storage section 122. The discharge device 42 is a device capable of discharging the gas from the inside of the gas storage section 122 to the outside of the gas storage section 122 at a constant flow rate. The discharge device 42 includes a gas flow controller, an air pump, and the like. The gas inside the gas storage section 122 can be discharged to the outside of the gas storage section 122 by the discharge device 42 through the discharge port 122A formed in the gas storage section 122.

[0081] The discharge device 42 may discharge the gas inside the gas storage section 122 from the discharge port 122A at a flow rate lower (for example, 9.9 L / min) than the flow rate of the gas supplied to the gas storage section 122 by the rectifying device 41 (for example, 10 L / min). In this case, the gas storage section 122 may be provided with an opening 122B for pressure adjustment. The opening 122B is an opening provided to avoid an increase in the internal pressure of the gas storage section 122 caused by the difference between the flow rate of the gas supplied to the gas storage section 122 and the flow rate of the gas discharged from the gas storage section 122. With such a configuration, the gas supplied from the inside of the culture tank 11 can be stably stored inside the gas storage section 122.

[0082] The second discharge unit 123 is a flow path for supplying the gas in the gas storage unit 122 to the odor measuring device 30. The second discharge unit 123 is, for example, a flexible tube. The second discharge unit 123 includes, for example, Teflon tube (registered trademark), nylon tube, and the like. One end of the second discharge unit 123 is connected to the gas storage unit 122, and the other end of the second discharge unit 123 is connected to the odor measuring device 30. A gas supply unit 40 is provided in the second discharge unit 123.

[0083] The odor measuring device 30 of the culture system 100A is provided in the discharge unit 12A. More specifically, the odor measuring device 30 is connected to the second discharge unit 123. The gas inside the culture tank 11 is supplied to the odor measuring device 30 at a constant flow rate by the gas supply unit 40. According to the configuration in which the odor measuring device 30 is provided in the discharge unit 12A, the odor measuring device 30 can constantly measure the odor contained in the gas inside the culture tank 11 discharged from the discharge unit 12A. Thereby, the user can constantly monitor the change in the culture state of the cultured cells during culture.

[0084] Note that the gas storage unit 122 may be detachable from the discharge unit 12A. When the gas storage unit 122 is removed from the discharge unit 12A, the connection between the first discharge unit 121 and the second discharge unit 123 is released.

[0085] According to the configuration in which the gas storage unit 122 is detachable from the discharge unit 12A, it is also possible to connect the gas storage unit 122 removed from the discharge unit 12A to a separately prepared odor measuring device 30. Thereby, it is also possible to perform off-line measurement.

[0086] 〔Embodiment 3〕 Other embodiments of the present invention will be described below with reference to FIG. 7. FIG. 7 is a schematic diagram showing an example of the configuration of a culture system 100B according to an embodiment of the present invention. For convenience of explanation, members having the same functions as those described in the above embodiment are denoted by the same reference numerals, and the description thereof will not be repeated. The culture system 100B of Embodiment 3 is different from the culture system 100 of Embodiment 1 in that the odor measuring device 30 is provided inside the culture tank 11B of the culture device 10B.

[0087] As shown in FIG. 7, the culture device 10B of the culture system 100B includes a culture tank 11C, a stirring unit 13, and an odor measuring device 30. The odor measuring device 30 is provided inside the culture tank 11B of the culture device B. The culture tank 11B may have airtightness so that anaerobic culture can be carried out, or may not have airtightness so that aerobic culture can be carried out. In particular, in the case of the culture device 10B capable of performing anaerobic culture, it is preferable to provide the odor measuring device 30 inside the culture tank 11B as in the present embodiment. In the case of the culture device 10B capable of performing anaerobic culture, nitrogen or the like may be supplied into the culture tank 11B from a gas supply unit (not shown). Further, in the case of the culture device 10B capable of performing aerobic culture, the discharge unit 12 may be provided.

[0088] According to the culture device 10B, there is no need to provide a structure for providing the odor measuring device 30 and a device for supplying the gas inside the culture tank 11B to the odor measuring device 30 in the culture tank 11B. Thereby, the culture device 10B can have a simple configuration. It is also possible to constantly monitor the gas inside the culture tank 11B.

[0089] [Embodiment 4] Another embodiment of the present invention will be described below with reference to FIG. 8. FIG. 8 is a schematic diagram showing an example of the configuration of a culture system 100C according to an embodiment of the present invention. For the sake of convenience of explanation, members having the same functions as those described in the above embodiment are denoted by the same reference numerals, and their descriptions will not be repeated. The culture system 100C of Embodiment 4 is different from the culture system 100 of Embodiment 1 in that the odor measuring device 30 is provided in the circulation unit 15 of the culture device 10C.

[0090] As shown in FIG. 8, the culture device 10C of the culture system 100C includes a culture tank 11C, a stirring unit 13, a circulation unit 15, an odor measuring device 30, and a gas supply unit 40. The culture tank 11C has airtightness so that anaerobic culture can be carried out. Note that nitrogen or the like may be supplied from a gas supply unit (not shown) into the culture tank 11C.

[0091] The culture tank 11C is provided with a circulation unit 15 through which the gas inside the culture tank 11C can circulate. The circulation unit 15 is, for example, a pipe. When the gas supply unit 40 provided in the circulation unit 15 is driven, the gas inside the culture tank 11C is supplied to the circulation unit 15 at a constant flow rate as shown by the arrow in FIG. 8. An odor measuring device 30 is provided in the circulation unit 15. The gas in the culture tank 11C supplied to the circulation unit 15 has its odor measured by the odor measuring device 30. After the odor is measured by the odor measuring device 30, the gas in the circulation unit 15 is supplied again into the culture tank 11C.

[0092] According to the configuration in which the culture device 10C includes the circulation unit 15, the odor measuring device 30 can measure the odor of the gas inside the culture tank 11C that circulates through the circulation unit 15. Thereby, even if there is a limitation in providing the odor measuring device 30 inside the culture tank 11C, the odor of the gas inside the culture tank 11C can be measured. Also, it is possible to constantly monitor the gas inside the culture tank 11C.

[0093] [Embodiment 5] Other embodiments of the present invention will be described below with reference to FIGS. 9 to 11. For convenience of explanation, members having the same functions as those described in the above embodiments are denoted by the same reference numerals, and their descriptions will not be repeated. The odor measuring device 30 according to Embodiment 5 is different in that it includes an odor sensor element 31c or an odor sensor element 31d as compared with the odor measuring device 30 according to Embodiment 1.

[0094] The odor measuring device 30 may include an odor sensor element 31c. With reference to FIG. 9, the configuration of the odor sensor element 31c will be described. FIG. 9 is a top view showing an example of the configuration of the odor sensor element 31c.

[0095] As shown in FIG. 9, the odor sensor element 31c includes an electrode 313 which is a metal wiring disposed on a substrate 311, and a circular odor substance receiving layer 315c formed on the electrode 313. The electrode 313 of the odor sensor element 31c includes a first metal wiring 313C and a second metal wiring 313D. That is, the odor sensor element 31c has a first metal wiring 313C and a second metal wiring 313D. The first metal wiring 313C and the second metal wiring 313D are each a metal wiring that functions as an electrode for measuring a change in the electrical conductivity of the odor substance receiving layer 315c. Further, as an example, the first metal wiring 313C is a first electrode composed of a metal wiring 313a and a metal wiring 313b, and the two metal wirings are arranged in a T shape so as to be perpendicular to each other. The second metal wiring 313D is a second electrode composed of two metal wirings 313c and 313d in the same manner as the first metal wiring 313C, and is configured such that the two metal wirings are arranged in a T shape so as to be perpendicular to each other. Further, the first metal wiring 313C and the second metal wiring 313D are arranged in parallel lines such that the metal wiring 313a and the metal wiring 313c face each other.

[0096] The first metal wiring 313C and the second metal wiring 313D are arranged in a T-shape with respect to each other, so that the first metal wiring 313C and the second metal wiring 313D can be disposed at a suitable distance from each other, and the resistance value of the electrode can be stabilized. For example, when the electrodes are arranged in a comb shape, the distance between the electrodes becomes short, and there is a risk that the resistance value of the electrodes becomes too small. Further, since the first metal wiring 313C and the second metal wiring 313D are arranged in a T-shape with respect to each other, in the coating step of the manufacturing method of the sensor element 31 described later, there are no uneven portions of the electrode that can prevent the spread of the slurry in the region where the slurry spreads, so that the slurry easily spreads. Further, since the slurry easily spreads, there is an effect that the thickness of the odor substance receiving layer 315 after drying becomes constant.

[0097] In FIG. 9, the metal wiring 313a and the metal wiring 313d are arranged on the front side of the substrate 311 (that is, the front side of the paper surface) and are in contact with the odor substance receiving layer 315c. On the other hand, the metal wiring 313b and the metal wiring 313c are each connected to the metal wiring 313a and the metal wiring 313d on the front side of the substrate 311 and penetrate the substrate 311 toward the back side. Therefore, the metal wiring 313b and the metal wiring 313c are not in contact with the odor substance receiving layer 315c. The diameter R of the odor substance receiving layer 315c is 0.2 mm or more and 5 mm or less. In FIG. 9, the shape of the odor substance receiving layer 315c included in the odor sensor element 31c is elliptical as an example, but is not limited thereto. When the shape of the odor substance receiving layer 315c is elliptical, the average of the minor axis and the major axis may be 0.2 mm or more and 5 mm or less. Further, the shape of the odor substance receiving layer 315c may be a perfect circle. The metal wiring 313a and the metal wiring 313d are in contact with the odor substance receiving layer 315c, but are not in contact with the odor substance permeable layer 317.

[0098] The odor measuring device 30 may include an odor sensor element 31d. With reference to FIG. 10, the configuration of the odor sensor element 31d will be described. FIG. 10 is a top view showing an example of the configuration of the odor sensor element 31d.

[0099] As shown in Fig. 10, the odor sensor element 31d includes electrodes 313 (first metal wiring 313C and second metal wiring 313D) disposed on a substrate 311, and a strip-shaped odorant receiving layer 315d formed on the electrodes 313. The length W of the width in the short direction of the odorant receiving layer 315d is 0.2 mm or more and 5 mm or less.

[0100] The electrodes of the odor sensor element 31 each have a first electrode and a second electrode, and the first electrode and the second electrode may be arranged in parallel linear, parallel curved, comb-shaped, or concentric circular shapes. The first electrode and the second electrode are preferably arranged symmetrically with respect to a line or point symmetry with each other regardless of which shape is adopted. By arranging the first electrode and the second electrode in this way, the odor measuring device 30 can measure the odorant contained in the gas with high accuracy.

[0101] Fig. 11 is a top view showing an example of the configuration of the odor sensor element 31c. As shown in Fig. 11, in the odor sensor element 31c, the first metal wiring 313C and the second metal wiring 313D are each connected to a pin 316 at an end where the first metal wiring 313C and the second metal wiring 313D do not face each other. The pin 316 is a conductive member for electrically connecting the first metal wiring 313C and the second metal wiring 313D to other members of the odor measuring device 30. Although not shown, the odor sensor element 31c and the odor sensor element 31d shown in Figs. 9 and 10 also include the pin 316 shown in Fig. 11.

[0102] 〔Other Embodiments〕 In the above-described Embodiment 1, the odor measuring device 30 is configured to measure the odor inside the culture tank 11 by connecting the gas sampling unit 20 to the odor measuring device 30. However, the configuration is not limited to this. For example, the odor measuring device 30 may be provided inside the gas sampling unit 20. In this case, the odor measuring device 30 measures the odor of the gas inside the gas sampling unit 20. As a result, by collecting the gas discharged from the discharge unit 12 or the gas inside the discharge unit 12 using the gas sampling unit 20 provided with the odor measuring device 30, it becomes possible to measure the odor of the gas inside the culture tank 11 with the odor measuring device 30. That is, it is not necessary to connect the gas sampling unit 20 to the odor measuring device 30.

[0103] 〔Example of Realization by Software〕 In the culture systems 100, 100A, 100B, and 100C, the control block (particularly the control unit 5) may be realized by a logic circuit (hardware) formed in an integrated circuit (IC chip) or the like, or may be realized by software.

[0104] In the latter case, the culture systems 100, 100A, 100B, and 100C include a computer that executes instructions of a program, which is software for realizing each function. This computer includes, for example, one or more processors and a computer-readable recording medium storing the above program. Then, in the above computer, when the above processor reads and executes the above program from the above recording medium, the object of the present invention is achieved. As the above processor, for example, a CPU (Central Processing Unit) can be used. As the above recording medium, in addition to "non-transitory tangible media" such as ROM (Read Only Memory), a tape, a disk, a card, a semiconductor memory, a programmable logic circuit, etc. can be used. Further, it may further include a RAM (Random Access Memory) etc. for expanding the above program. Further, the above program may be supplied to the above computer via any transmission medium (communication network, broadcast wave, etc.) capable of transmitting the program. Note that one aspect of the present invention can also be realized in the form of a data signal embedded in a carrier wave, in which the above program is embodied by electronic transmission.

[0105] 〔Summary〕 The culture system according to Aspect 1 of the present invention includes a culture tank capable of accommodating cultured cells, an odor measurement unit that measures the odor inside the culture tank accommodating the cultured cells, and an information processing device that outputs an estimation result of estimating the culture state of the cultured cells based on a measurement signal output from the odor measurement unit.

[0106] In the culture system according to Aspect 2 of the present invention, in the above Aspect 1, the culture state may be correlated with the expression level of a protein produced from the cultured cells.

[0107] In the culture system according to Aspect 3 of the present invention, in the above Aspect 2, the information processing device may input the expression level of the protein based on the measurement signal output from the odor measurement unit into a learned model learned by machine learning using teacher data, and output an estimation result of the culture state.

[0108] In the culture system according to Aspect 4 of the present invention, in any one of the above Aspects 1 to 3, the odor measurement unit may be provided in a discharge unit that discharges the gas inside the culture tank to the outside of the culture tank.

[0109] In the culture system according to Aspect 5 of the present invention, in the above Aspect 4, the discharge unit may be provided with a gas storage unit that can store the gas inside the culture tank and supply the stored gas to the odor measurement unit.

[0110] In the culture system according to Aspect 6 of the present invention, in the above Aspect 5, the gas storage unit may be detachably provided in the discharge unit.

[0111] In the culture system according to Aspect 7 of the present invention, in any one of the above Aspects 1 to 3, the odor measurement unit may be provided inside the culture tank.

[0112] In the culture system according to Aspect 8 of the present invention, in any one of the above Aspects 1 to 3, the culture tank has airtightness, and the odor measurement unit may be provided in a circulation unit through which the gas inside the culture tank can circulate.

[0113] In the culture system according to Aspect 9 of the present invention, in any one of the above Aspects 1 to 8, the cultured cells may be Escherichia coli.

[0114] The culture apparatus according to Aspect 10 of the present invention includes a culture tank that can accommodate cultured cells, and an odor measurement device that measures the odor inside the culture tank.

[0115] The control method of the culture system according to Embodiment 11 of the present invention includes a measurement signal acquisition step of acquiring a measurement signal output from an odor measurement unit that measures the odor inside a culture tank containing cultured cells, and an estimation step of outputting an estimation result obtained by estimating the culture state of the cultured cells based on the measurement signal.

[0116] The present invention is not limited to the above-described embodiments, and various modifications are possible within the scope shown in the claims. Embodiments obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention.

Description of Reference Numerals

[0117] 10 Culture apparatus 11 Culture tank 12 Discharge part 15 Circulation part 30 Odor measurement device 31 Sensor element 50 Information processing device 61 Trained model 100 Culture system 122 Gas storage part

Claims

1. A culture tank capable of accommodating cultured cells; an odor measuring unit for measuring the odor inside the culture tank containing the cultured cells; an information processing device that outputs an estimation result of estimating a culture state of the cultured cells based on the measurement signal output from the odor measuring unit; A culture system comprising:

2. The culture condition correlates with the expression level of a protein produced from the cultured cells. The culture system according to claim 1 .

3. The information processing device inputs the expression level of the protein based on the measurement signal output from the odor measuring unit into a trained model trained by machine learning using teacher data, and outputs the estimation result of the culture state. The culture system according to claim 2 .

4. The odor measuring unit is The exhaust section is provided for exhausting the gas inside the culture tank to the outside of the culture tank. The culture system according to claim 1 .

5. The exhaust unit is provided with a gas storage unit capable of storing gas inside the culture tank and supplying the stored gas to the odor measuring unit. The culture system according to claim 4.

6. The culture system according to claim 5 , wherein the gas storage section is removably provided in the exhaust section.

7. The odor measuring unit is provided inside the culture tank. The culture system according to claim 1 .

8. The culture tank is airtight, The odor measuring unit is provided in a circulation unit that can circulate the gas inside the culture tank. The culture system according to claim 1 .

9. The culture system according to claim 1 , wherein the cultured cells are Escherichia coli.

10. A culture tank capable of accommodating cultured cells; An odor measuring device for measuring the odor inside the culture tank; A culture apparatus comprising:

11. a measurement signal acquiring step of acquiring a measurement signal output from an odor measuring unit that measures the odor inside a culture tank containing cultured cells; an estimation step of outputting an estimation result of estimating a culture state of the cultured cells based on the measurement signal; A method for controlling a culture system comprising:

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