A system for estimating the dynamics of a measurement target system using oxidation-reduction potential

Abstract

The subject of the present invention is to provide a system for inferring the dynamics of a measurement object system, which not only provides information on whether the culture solution is aerobic or anaerobic, but also provides data for determining the culture operation and optimizing various conditions of the culture solution. The solution of the present invention is a system for inferring the dynamics of a measurement object system, comprising: a reference electrode; a first working electrode; a second working electrode, which is different from the first working electrode in at least the material or surface processing; a third working electrode, which is different from the first working electrode and the second working electrode in at least the material or surface processing; and an information storage unit, which receives first potential information, second potential information, and third potential information and stores information including the first potential information, the second potential information, and the third potential information, wherein the first potential information is about the redox potential in the reference electrode and the first working electrode, the second potential information is about the redox potential in the reference electrode and the second working electrode, and the third potential information is about the redox potential in the reference electrode and the third working electrode.

Description

Technical Field

[0001] An invention described in this specification relates to a system for estimating the dynamics of a measurement target system using oxidation-reduction potential. Background Art

[0002] Japanese Patent Application Publication No. 2007-33344 (Patent Document 1) describes a redox potential measuring device. In the redox potential measuring device described in this document, for example, a platinum electrode is used as a measuring electrode, and a silver / silver chloride electrode is used as a reference electrode. In addition, this document describes that any of various types of reference electrodes can be used as the reference electrode (paragraph

[0030] ).

[0003] For example, when the culture conditions of microorganisms are estimated using an oxidation-reduction potential measuring device, the degree to which the culture solution is aerobic or anaerobic can be obtained as an indicator.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Publication No. 2007-33344 Summary of the invention

[0007] Problems to be solved by the invention

[0008] An object of an invention described in this specification is to provide a system for estimating the dynamics of a measurement target system, which not only provides information on whether a culture medium is aerobic or anaerobic, but also provides data for determining culture operations and optimizing various conditions of the culture medium.

[0009] Technical solutions to problems

[0010] An invention described in this specification is basically based on the knowledge that the dynamics of a measurement target system can be estimated by using a plurality of types of working electrodes (measuring electrodes) and measuring the redox potential between the electrodes and a reference electrode.

[0011] The first invention described in this specification relates to a system for estimating the dynamics of a measurement target system. The system 1 for estimating the dynamics of a measurement target system comprises: a reference electrode 3, a first working electrode 5, a second working electrode 7 having at least a material or surface processing different from that of the first working electrode 5, a third working electrode 9 having at least a material or surface processing different from that of the first working electrode 5 and the second working electrode 7, and an information storage unit 11.

[0012] The information storage unit 11 is an element for receiving first potential information, second potential information and third potential information and storing information including the first potential information, the second potential information and the third potential information, wherein the first potential information is about the redox potential in the reference electrode 3 and the first working electrode 5, the second potential information is about the redox potential in the reference electrode 3 and the second working electrode 7, and the third potential information is about the redox potential in the reference electrode 3 and the third working electrode 9.

[0013] The system is a system that can be used to infer the dynamics of the measurement target system. That is, for an object (e.g., culture medium) for which various conditions have been adjusted, by obtaining information including first potential information, second potential information, and third potential information, information for analyzing the dynamics of the measurement target system can be collected. This data is, for example, multivariate data that can be used for machine learning, etc.

[0014] The dynamics estimation unit 13 is an element for estimating the dynamics of the target system using the first potential information, the second potential information, and the third potential information stored in the information storage unit 11 .

[0015] A preferred example of use of this system is a system for estimating the dynamics of a system containing organisms and suggesting an optimization method or automatically performing optimization.

[0016] Effects of the Invention

[0017] One invention described in this specification not only provides information on whether a culture medium is aerobic or anaerobic, but also provides data for determining a culture operation and optimizing various conditions of the culture medium. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a block diagram showing an example of the configuration of a system for estimating the dynamics of a measurement target system.

[0019] Figure 2 A block diagram showing the basic structure of a computer.

[0020] Figure 3 This is a schematic diagram of the culture and measurement system of the embodiment.

[0021] Figure 4 It is a graph replacing the drawing showing representative culture results and time series data in the culture performed in the Examples.

[0022] Figure 5 This is a graph replacing a drawing showing a comparison of the coefficient of determination of lactic acid production efficiency performed in Examples. DETAILED DESCRIPTION

[0023] The specific embodiments of the present invention are described below using the drawings. The present invention is not limited to the embodiments described below, and includes modifications appropriately made by those skilled in the art from the following embodiments within the known range.

[0024] Figure 1 The present invention is a block diagram showing an example of a system for estimating the dynamics of a measurement target system. The dynamics of the measurement target system include the optimal conditions or various changes of the measurement target system. Examples of the dynamics of the measurement target system include the living conditions, activity conditions, dispersal conditions, proliferation conditions, fermentation conditions, the amount of predetermined metabolites, the amount of decomposed products, the preferred conditions for a predetermined purpose, and the unpreferable conditions for a predetermined purpose of organisms living in the measurement target system.

[0025] like Figure 1 As shown, the system 1 for estimating the dynamics of the measurement object system comprises: a reference electrode 3, a first working electrode 5, a second working electrode 7, a third working electrode 9 and an information storage unit 11. In this state, data for obtaining the optimal conditions can be stored in the information storage unit 11. The system 1 may also further include an optimal condition estimation unit 13. The optimal condition estimation unit 13 can read the data recorded in the information storage unit 11 and estimate the optimal conditions by performing various analyses. The second working electrode 7 refers to an electrode that is different from the first working electrode 5 at least in material or surface processing. The third working electrode 9 refers to an electrode that is different from the first working electrode 5 and the second working electrode 7 at least in material or surface processing.

[0026] Working electrodes 5, 7, 9 are electrodes for causing the measured object to act and measuring the redox potential between the reference electrode 3. There are at least three working electrodes. System 1 may also include more than three (e.g., four, five, six, and seven) working electrodes. The plurality of working electrodes are preferably insulated from each other. Then, preferably, the potential difference is measured independently by a voltmeter disposed between each working electrode and the reference electrode 3.

[0027] The working electrode can be any electrode that can be in contact with an object (usually containing a liquid) and has conductivity. Each working electrode is different in at least material or surface processing. Examples of materials for working electrodes are platinum, gold, carbon, carbon allotropes (glassy carbon, diamond, graphene, carbon nanotubes, fullerenes) and alloys. Differences in materials also include differences in composition ratios. Differences in surface processing include differences in surface roughness of the electrode, differences in atomic configuration on the electrode surface, and differences in shape. The shape of each working electrode can be appropriately adjusted according to its intended use.

[0028] The system 1 for estimating the dynamics of the measurement target system is preferably a computer-aided system. This system is basically implemented by a computer (and software). This system is preferably a system that automatically processes by a computer. In addition, when there is input from a user, this system can also process the input as a kind of information. Each element or element represented by a part in this specification functions as a unit that performs various processes in a computer.

[0029] Figure 2 This is a block diagram showing the basic structure of a computer. As shown in this figure, the computer has an input unit 21, an output unit 23, a control unit 25, a computing unit 27 and a storage unit 29. Each element is connected through a bus 31, etc., and information can be transmitted and received. For example, a control program can be stored in the storage unit, and various information can also be stored. When predetermined information has been input from the input unit, the control unit reads the control program stored in the storage unit. Then, the control unit appropriately reads the information stored in the storage unit and transmits it to the computing unit. In addition, the control unit appropriately transmits the input information to the computing unit. The computing unit uses the various information received to perform computing processing and stores it in the storage unit. The control unit reads the computing results stored in the storage unit and outputs them to the output unit. In this way, various processing is performed. The various processing units are each unit.

[0030] The information storage unit 11 is an element for receiving first potential information, second potential information and third potential information and storing information including the first potential information, the second potential information and the third potential information, wherein the first potential information is about the redox potential in the reference electrode 3 and the first working electrode 5, the second potential information is about the redox potential in the reference electrode 3 and the second working electrode 7, and the third potential information is about the redox potential in the reference electrode 3 and the third working electrode 9.

[0031] The storage unit 29 of the computer functions as the information storage unit 11. The voltmeter corresponding to each working electrode inputs information about the measured voltage (and oxidation-reduction potential) to the input unit 21 of the computer. Then, the computer stores the input potential information in the information storage unit 11.

[0032] The system is a system that can be used to infer the dynamics of the system. That is, by obtaining information including first potential information, second potential information, and third potential information for an object (e.g., a culture solution containing an organism) for which various conditions have been adjusted, information for analyzing the dynamics of the system can be collected. This data is, for example, multivariate data that can be used for machine learning.

[0033] The dynamics estimation unit 13 is an element for estimating the dynamics of the target system using the first potential information, the second potential information, and the third potential information stored in the information storage unit 11 .

[0034] The system may further receive information about the measurement object system, i.e., measurement object system information, and use the received measurement object system information and the first to third potential information to infer the dynamics of the system being the object. The measurement object system information may be obtained, for example, by using various sensors. Examples of measurement object system information are temperature, humidity, air pressure, turbidity of the culture solution, acidity, concentration of the target substance, and the presence or absence of the target substance. Furthermore, the system may also store information related to information about changes in the system (e.g., the amount or concentration of the dripped substance), i.e., system change information. By using the stored system change information, measurement object system information, and the first to third potential information, the correlation between the measurement object system information and the first to third potential information when the system is changed can be obtained. By repeatedly analyzing the correlation, the dynamics of the measurement object system can be inferred.

[0035] For example, consider a case where the system infers the dynamics of the turbidity (e.g., OD660) of the target culture fluid. In this case, the system receives information about light absorption from a spectrometer that irradiates light together with information such as temperature or pH value for the target culture fluid. At this time, as described above, the system stores information including first potential information, second potential information, and third potential information together with the information. Then, using the stored multiple data as multivariate data, the dynamics of OD660 are analyzed and inferred. And in the case where the inferred dynamics are not preferred, the dynamics of the case where the pH value or temperature is changed can be similarly inferred. In this way, the system can infer the dynamics of the measured object system and support the most suitable culture.

[0036] For example, consider a case where the system infers the dynamics of the concentration of a product to be targeted (e.g., lactic acid production via fermentation). In this case, the system receives data on the quantitative lactic acid concentration of the culture solution to be targeted together with information such as temperature or pH value. At this time, as described above, the system stores information including the first potential information, the second potential information, and the third potential information together with these information. Then, using the stored multiple data as multivariate data, machine learning is performed and the relationship between the time series changes of the lactic acid concentration and the time series changes of other data is derived. By using this learner, the dynamics of the lactic acid concentration can be inferred from the data that can be obtained in the culture. And in the case where the inferred dynamics are not preferred, the dynamics of the situation where the pH value or temperature is changed can be similarly inferred. In this way, the system can infer the dynamics of the measured object system and support the most suitable culture.

[0037] A preferred use of this system is to estimate optimal conditions in a system containing organisms.

[0038] Hereinafter, an example of utilizing the system of the present invention will be described.

[0039] Water system monitoring

[0040] The multi-dimensional redox potential changes of water systems accompanying life activities can be monitored in multiple dimensions. The potential information from multiple electrodes in various phenomena is stored as multivariate data. Various analyses such as patterning can be performed by machine learning of the multivariate data.

[0041] Description of biological phenomena

[0042] In addition to oxygen, nitrogen, sulfur, etc., which are called active molecular species, various trace elements adopt various redox states. By measuring the multi-dimensional redox states with multiple types of conductor electrode potentials, biological phenomena can be described in more detail.

[0043] Microbial Manufacturing

[0044] In the process of producing substances by microorganisms, various components in the culture solution that become raw materials and are required for the life activities of microorganisms are consumed. In the process of decomposition / generation, the redox state in the culture solution changes multivariately. Potential information from multiple electrodes is stored as multivariate data. Various analyses such as patterning can be performed by machine learning of the multivariate data. For example, potential information of a situation where microorganisms have become extinct is used and patterned by machine learning. Then, when the potential information of the new system is correlated with the patterned potential information and a correlation is shown, the extinction of microorganisms can be prevented by changing the state of the system.

[0045] beer

[0046] Depending on the state of the raw materials such as barley, hops, brewing water, and brewer's yeast, the redox state of the fermentation process will be different. The redox state will also change by changing the temperature during fermentation, and as a result, the degree of completion of the beer will also change. By monitoring the potential information, the fermentation status can be grasped. For example, the potential information during normal fermentation is stored as data and machine learning is performed. Then, when the potential information of the new system is different from the pattern of the potential information that has been machine-learned, it is inferred that the fermentation conditions are abnormal and the quality of the beer may change. In this way, by using multiple potential information as data, the quality of beverages such as beer can be kept constant. Examples of beverages are alcoholic beverages including wine, sake, whiskey, etc., and beverages accompanied by fermentation (drinkable yogurt, etc.).

[0047] Fermented seasonings

[0048] Fermented seasonings such as soy sauce, miso, koji, mirin, vinegar, etc.

[0049] The raw materials such as soybeans, wheat, rice, koji, yeast, as well as the temperature, redox state and degree of completion of the product can be managed.

[0050] Organic wastewater treatment

[0051] Since wastewater treatment involves a complex microbial system, the treatment status of organic wastewater can be understood by using potential information.

[0052] Antibody Medicine

[0053] For example, in antibody (protein) production using CHO cells (animal cells), antibodies of constant quality can be produced by using potential information.

[0054] Regenerative Medicine

[0055] The proliferation efficiency and differentiation induction efficiency of stem cells can be guaranteed to be constant in quality by using the potential information of the differentiation state.

[0056] Algae

[0057] In the cultivation of algae, constant quality can be ensured by using potential information.

[0058] Hydroponics

[0059] Relationship between the redox state of the nutrient solution in direct contact with the rhizosphere and vegetable growth in hydroponic cultivation.

[0060] paddy fields

[0061] In rice cultivation, constant quality can be ensured by using potential information.

[0062] Corrosion of circulating water system pipes

[0063] In terms of circulating water system piping, the status can also be understood by using potential information.

[0064] Farming

[0065] The deterioration of water quality in aquaculture farms, the growth of fish, the occurrence of diseases, etc. can also be managed or optimized by using potential information.

[0066] Pollution / purification of harbors, waterways, lakes and swamps

[0067] In terms of pollution / purification of ports, waterways, and lakes, the status can be understood by using potential information.

[0068] aquarium

[0069] In aquariums, the situation can also be understood by using potential information.

[0070] Wearable Terminal

[0071] By using it in a wearable terminal, data on the redox state of the body surface (sweat, etc.) can be obtained, thereby understanding the wearer's health status or psychological condition.

[0072] Intraoral Sensor

[0073] It can analyze the relationship between the redox potential in the mouth and tooth decay, periodontal disease, bad breath, oral ulcers, and health status.

[0074] Urine sensor

[0075] By analyzing urine using this system, cancer can be detected early and the health status of the subject can be understood. In this case, for example, multiple potential information when measuring urine of a certain cancer patient is stored, machine learning is performed to model it, and the results are stored. Then, by analyzing the potential information of the measured urine of the subject, the possibility of the subject suffering from a certain cancer can be analyzed.

[0076] Composting

[0077] In the case of composting, the status can also be understood by using potential information.

[0078] Example showing the use of the system of the present invention for lactic acid production by microorganisms

[0079] Figure 3 Schematic diagram of the culture and measurement system of the embodiment. Figure 3 As shown, this culture control device 41 has: a fermentation tank 42, a stirring blade 43, an air blowing device 44, an exhaust gas measuring device 45, a sampler 46, a heating belt 47, a sodium hydroxide addition control pump 48, a thermometer 49, a pH meter 50, a dissolved oxygen meter 51, a platinum electrode 52, a gold electrode 53, a glassy carbon electrode 54, a reference electrode 55, a voltage recorder 56 and a computer 57.

[0080] The strain used produces lactic acid using glucose as a substrate. A culture medium consisting of glucose and yeast extract is placed in a fermenter, and the previously cultured bacteria are added, and the culture is carried out while air is ventilated from a dispersion tube.

[0081] The redox potential sensor used was connected to a commercially available voltage recorder in a manner that platinum, gold, and glassy carbon were used as working electrodes and a silver chloride electrode was used as a common reference electrode.

[0082] Other measurement items are temperature, pH value, dissolved oxygen concentration, exhaust oxygen concentration, and exhaust carbon dioxide concentration. Thermometer, pH meter, and dissolved oxygen meter are installed in the fermenter. The pH value is monitored by the culture control device. When the pH value is lower than the set pH value, the pump is controlled to drip sodium hydroxide solution to keep the pH value constant. In addition, the exhaust oxygen concentration and exhaust carbon dioxide concentration are also measured by the culture control device. These data are finally recorded in the computer.

[0083] Using this system, a total of 40 experiments were conducted with an initial glucose concentration of 120 g / L, a temperature of 34.5 to 37.0 degrees Celsius, and a pH range of 7.34 to 8.13. The culture fluid was extracted 20, 220, 420, 620, 820, 1020, 1220, and 1420 minutes after inoculation, and the OD660, glucose concentration, and lactic acid concentration were quantified. Spline interpolation was performed on the data to obtain the OD660, glucose concentration, and lactic acid concentration during the culture period.

[0084] Figure 4 It is a graph replacing the drawing showing representative culture results and time series data in the culture performed in the Examples.

[0085] Based on these data, the data of temperature, pH value, dissolved oxygen concentration, exhaust oxygen concentration, exhaust carbon dioxide concentration, OD660 and redox potential were used as inputs according to the time after 60, 120, 180, 240, 300, 360, 420, 480 and 540 minutes of inoculation, and a learning model with lactic acid production efficiency (lactic acid concentration when the glucose concentration is as low as 20g / L) as output was constructed using random forest. When only platinum electrode was used as redox potential data, the coefficient of determination of production efficiency was 0.987, 0.979, 0.991, 0.986, 0.984, 0.989, 0.985, 0.988, 0.977 (average 0.985) in the order of time after inoculation. In addition, the coefficients of determination when the data of the redox potential were not taken into account were 0.982, 0.912, 0.986, 0.985, 0.978, 0.99, 0.963, 0.979, and 0.964 (average 0.971), respectively.

[0086] Next, the gold electrode and glassy carbon electrode were added as data of redox potential and the learning model was constructed. As a result, the coefficient of determination of production efficiency was 0.987, 0.986, 0.994, 0.990, 0.991, 0.991, 0.992, 0.992, and 0.989 (average 0.990), which was significantly improved (P value = 0.0009: paired t test).

[0087] Figure 5This is a graph replacing the figure showing the comparison of the coefficient of determination for lactic acid production efficiency in the examples. This shows the following result: compared with the conventional redox potential data of a single electrode, the redox potential data of multiple electrodes provided by the present invention is more useful as an indicator for estimating the dynamics of the culture system.

[0088] Industrial Applicability

[0089] The present invention relates to a system for estimating the dynamics of a measurement target system, and thus can be used in various technical fields such as the experimental equipment industry, the pharmaceutical industry, and biotechnology.

[0090] Description of Reference Numerals

[0091] 1System for inferring dynamics

[0092] 3. Reference electrode

[0093] 5. First working electrode

[0094] 7. Second working electrode

[0095] 9Third working electrode

[0096] 11Information storage unit

[0097] 13Optimization condition estimation unit

Claims

1. A system for estimating the dynamics of a measurement target system, characterized in that: Include: Reference electrode; a first working electrode; A second working electrode, which is different from the first working electrode in at least material or surface processing; A third working electrode, which is different from the first working electrode and the second working electrode in at least material or surface processing; as well as an information storage unit, which receives first potential information, second potential information, and third potential information and stores information including the first potential information, the second potential information, and the third potential information, wherein the first potential information is about the redox potential between the reference electrode and the first working electrode, the second potential information is about the redox potential between the reference electrode and the second working electrode, and the third potential information is about the redox potential between the reference electrode and the third working electrode; The system further receives information about the measurement target system, namely, measurement target system information. The system stores information related to information causing changes to the system, namely, system change information, By using the measurement target system information, the system change information, and the first potential information, the second potential information, and the third potential information stored in the information storage unit, a correlation between the measurement target system information and the first to third potential information when the system is changed is obtained; By continuously repeating the analysis of the correlation while the electrodes are installed in the measurement object, the dynamics of the measurement object system can be estimated.

2. The system for estimating the dynamics of a measurement target system according to claim 1, characterized in that: Further including: The optimization condition estimation unit estimates the optimization condition of the target system using the first potential information, the second potential information, and the third potential information stored in the information storage unit.

3. The system for estimating the dynamics of a measurement target system according to claim 1, characterized in that: Used for support of operations in systems containing biological organisms.

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