Biomedical analyzer and program

Abstract

To provide a bioanalytical device that measures biological signals from a subject, and simultaneously acquires and displays information about the subject's physical condition based on those biological signals. [Solution] A bioanalytical device comprising: a biosignal detection unit for sequentially acquiring biosignals from a subject; a differential circuit unit for differentiating the biosignal output from the biosignal detection unit and acquiring the differential value of the biosignal; a physical state detection unit for detecting the physical state of the subject based on the differential value; and a display unit for displaying a graph representing the biosignal and the differential value, and information about the physical state, wherein the device performs the acquisition of the differential value of the biosignal in the differential circuit unit, the detection of the physical state in the physical state detection unit, and the display of a graph representing the biosignal and the differential value, and information about the physical state in the display unit, in parallel with the sequential acquisition of the biosignal in the biosignal detection unit.

Description

Technical Field

[0001] The present invention relates to a biological analysis apparatus and a program for analyzing the physical state of a subject based on biological signals.

Background Art

[0002] In recent years, with the increasing interest in health, there has been a growing need to selectively detect substances in biological fluids such as sweat, saliva, urine, tears, and blood in order to monitor the physical state. Among them, non-invasive measurements that do not involve procedures that harm the subject's body, such as blood collection, have attracted attention.

[0003] There is an electrochemical sensor that measures a specific analyte such as a biological substance by an electrical signal from an electrode in contact with a solution containing the analyte. Furthermore, when a film containing a substance having the ability to selectively recognize the analyte is formed on the electrode of the electrochemical sensor, more selective and sensitive detection of the analyte becomes possible.

[0004] In non-invasive measurement of biological substances, the analyte can be monitored over time while the measurement device is attached to the subject's body. Furthermore, such monitoring of the analyte over time makes it possible to analyze the state transition of the subject's body. Patent Document 1 discloses a biological analysis apparatus that acquires the change over time of the lactic acid value in the sweat of a subject during exercise and analyzes a transition point indicating the timing of the state transition of the subject based on the amount of change, and a program for operating the same.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] The present invention provides a bioanalytical device that measures biosignals from a subject and displays the acquired biosignals, their rate of change, and information about the subject's physical condition detected based on the rate of change of the biosignals. [Means for solving the problem]

[0007] In one embodiment, the present invention is a bioanalytical device, A biosignal detection unit for sequentially acquiring biosignals from a subject; A differentiation circuit unit for differentiating the biological signal output from the biological signal detection unit and obtaining the differential value of the biological signal; A body state detection unit for detecting the physical state of the subject based on the differential value; and, A graph representing the biosignal and the differential value, and a display unit for displaying information about the physical state. Equipped with, This device performs the acquisition of the differential value of a biological signal in the differential circuit section, the detection of a physical state in the physical state detection section, and the display of a graph representing the biological signal and the differential value, as well as information about the physical state, in parallel with the sequential acquisition of the biological signal in the biological signal detection section. We provide a bioanalysis device.

[0008] In another embodiment, the present invention is a program for performing the following steps (a) to (c), (a) A process of sequentially acquiring biosignals and their differential values ​​from the subject, (b) A step of detecting the physical state of the subject based on the differential value, (c) A step of displaying a graph representing the biosignal and the differential value, and information about the physical state. Steps (b) and (c) are performed in parallel with step (a). We provide the program. [Effects of the Invention]

[0009] The bioanalytical device and program of the present invention enable the sequential acquisition and display of information regarding the biosignals from a subject, their rate of change, and the subject's physical state detected based on the rate of change, while simultaneously measuring the biosignals from the subject. Therefore, according to the present invention, information regarding the subject's biosignals and their rate of change, as well as their physical state or its changes, can be provided to the subject and their observer in real time during the measurement. Furthermore, according to the present invention, the subject and their observer can visually observe the changes in the biosignals, their rate of change, and physical state from the start of the measurement. [Brief explanation of the drawing]

[0010] [Figure 1] A conceptual diagram of one embodiment of the bioanalysis device of the present invention. [Figure 2] A conceptual diagram showing one embodiment of a bioanalytical device attached to a subject. [Figure 3] A flowchart illustrating one embodiment of the operating process of a bioanalytical device. [Figure 4] The lactic acid concentration measurement system used in Example 1. [Figure 5] A graph plotting the current (μA) and its time derivative (A / s) measured in Example 1 against time (s). [Figure 6] Correlation between the time derivative of the current measured in Example 1 (A / s) and the rate of change of lactic acid concentration in the solution (mM / s). [Figure 7] An example of a metabolic mode display. The time derivative of the current is below the threshold (dotted line), and the metabolic mode displayed is "fat metabolism mode". [Figure 8] An example of a metabolic mode display. The time derivative of the current has reached the threshold (dotted line), and the metabolic mode displayed is "glucose metabolism mode". [Modes for carrying out the invention]

[0011] The present invention provides a biological analysis apparatus and a program that enable the sequential acquisition and display of the rate of change of a biological signal from a subject and information on the physical state of the subject detected based on the rate of change while measuring the biological signal from the subject.

[0012] 〔Biological analysis apparatus〕 The biological analysis apparatus of the present invention (hereinafter also referred to as the apparatus of the present invention) includes the following: A biological signal detection unit for sequentially acquiring a biological signal from a subject; A differential circuit unit for differentiating the biological signal output from the biological signal detection unit to obtain a differential value of the biological signal; A physical state detection unit for detecting the physical state of the subject based on the differential value; and, A display unit for displaying a graph representing the biological signal and the differential value and information on the physical state.

[0013] Subjects to which the apparatus of the present invention is applied include mammals including humans and non-human mammals. It is preferable that the subject is in a situation where the physical state can transition. More preferably, the biological analysis apparatus of the present invention is applied to a subject during exercise.

[0014] The biological signal acquired from the subject may be any signal that can reflect the transition of the physical state, and it is preferable that the signal can be continuously acquired from the subject. For example, signals reflecting the concentration of substances in biological fluids, heart rate, blood O2 concentration (oxygen saturation), CO2 concentration in exhaled breath, etc. can be mentioned. Examples of the substances in the biological fluid include lactic acid concentration in sweat, lactic acid concentration in blood, alcohol concentration in sweat, alcohol concentration in blood, glucose concentration in sweat, glucose concentration in blood, etc.

[0015] The detected physical state depends on biological signals. For example, if the biological signal is sweat or blood lactate concentration, or exhaled CO2 concentration, the physical state that can be detected may be whether the metabolic state is predominantly fat metabolism or glucose metabolism. Also, for example, if the biological signal is heart rate, the physical state that can be detected may be exercise load or heart health. Also, for example, if the biological signal is blood O2 concentration (oxygen saturation), the physical state that can be detected may be the effect of oxygen supply or the state of the respiratory system.

[0016] The configuration of the apparatus of the present invention will be described below.

[0017] <Biometric Signal Detection Unit> The biosignal detection unit in the apparatus of the present invention includes a sensor that is attached to the subject and sequentially acquires the aforementioned biosignals from the subject. Preferably, the sensor is configured to acquire the biosignals from a subject in a state where the physical state may change (for example, during activity or exercise). For example, when acquiring the concentration of lactic acid in sweat, the sensor is attached to the skin of the subject. The site where the sensor is attached is not particularly limited, but areas with many sweat glands (for example, the forehead, arms, back, wrists, etc.) are preferred. Preferably, the acquired biosignals are detected as electrical signals or converted into electrical signals and output to the differential circuit unit described later.

[0018] Preferably, the sensor is an electrochemical sensor for measuring the concentration of a substance in a biological fluid. The electrochemical sensor comprises a working electrode containing a substance capable of recognizing the substance to be measured in the biological fluid. In one embodiment, the electrochemical sensor is a two-electrode system consisting of a working electrode and a counter electrode (reference electrode). The working electrode and the counter electrode are arranged so that they can each come into contact with the biological fluid containing the substance to be measured, but do not come into electrical contact with each other. In another embodiment, the electrochemical sensor is a three-electrode system consisting of a working electrode, a counter electrode, and a reference electrode (reference electrode). The working electrode, the counter electrode, and the reference electrode are arranged so that they can each come into contact with the biological fluid containing the substance to be measured, but do not come into electrical contact with each other.

[0019] The electrical signal output by the electrochemical sensor may be any signal, such as voltage, current, power, or frequency and phase as an AC signal, but voltage or current is preferred.

[0020] If the electrochemical sensor is a three-electrode system, the sensor may be equipped with a potential control mechanism that controls the potential of the counter electrode so that the potential of the working electrode relative to the reference electrode is a predetermined value. If the electrical signal output by the electrochemical sensor is a current flowing between the working electrode and the counter electrode, the sensor may be equipped with a mechanism that sets the potential of the working electrode relative to the counter electrode to a predetermined value. Alternatively, if the electrical signal output by the electrochemical sensor is the impedance between the working electrode and the counter electrode, the sensor may be equipped with a mechanism that applies a predetermined DC voltage or an AC voltage with a predetermined amplitude and frequency between the working electrode and the counter electrode.

[0021] Preferably, the electrochemical sensor is an enzyme sensor and comprises a working electrode containing an enzyme that recognizes the substance to be measured. For example, when acquiring the concentration of lactate in sweat, the enzyme is preferably lactate oxidase. When the sweat of the subject comes into contact with the enzyme sensor, the electrical properties of the working electrode change due to the reaction between the lactate in the sweat and the enzyme, and as a result, the sensor outputs an electrical signal that reflects the concentration of lactate in the sweat. Preferably, the electrical signal is an electric current or an open-circuit potential (OCP).

[0022] The biological signals of the subject acquired by the biological signal detection unit are output from the biological signal detection unit to the differentiating circuit unit. If the acquired biological signals are weak, they may be amplified by an amplification circuit or the like before being sent to the differentiating circuit unit.

[0023] <Differential circuit section> The differential circuit in the apparatus of the present invention differentiates the biological signal output from the biological signal detection unit with respect to time to obtain the differential value (time derivative) of the biological signal. The time derivative represents the rate of change of the biological signal with respect to time (amount of change over a predetermined period of time).

[0024] Examples of methods for differentiating the aforementioned biological signal include differentiating an electrical signal representing the biological signal output from a biological signal detection unit using an electrical differentiating circuit, and converting the biological signal digitally and calculating the amount of change in the biological signal over a predetermined time period using a computer or the like from the digital data. Conventional known circuits can be used for the electrical differentiating circuit. The electrical differentiating circuit may be either a passive differentiating circuit or an active differentiating circuit. Examples of the passive differentiating circuit include a CR differentiating circuit using a capacitor and a resistor, and an RL differentiating circuit combining an inductor and a resistor. Examples of the active differentiating circuit include a differentiating circuit using an operational amplifier, a capacitor, and a resistor, and a differentiating circuit using an operational amplifier, an inductor, and a resistor. Of these, an active differentiating circuit is preferred from the viewpoint of the accuracy of the calculated differential value, and furthermore, a differentiating circuit using an operational amplifier, a capacitor, and a resistor is more preferred from the viewpoint of miniaturizing the circuit.

[0025] In one embodiment, the differentiation circuit is an electrical differentiation circuit and is electrically connected to the electrochemical sensor of the biosignal detection unit. In another embodiment, differentiation of the biosignal is performed by a computer.

[0026] <Body State Detection Unit> The physical state detection unit in the apparatus of the present invention detects the physical state of a subject based on the differential value of a biological signal output from the differential circuit unit. For example, the physical state detection unit detects whether the differential value is greater than or equal to a predetermined value. Alternatively, the physical state detection unit can detect the timing at which the differential value rises above a predetermined value or decreases below a predetermined value. The predetermined value is a threshold for whether or not the subject's physical state changes, and the timing at which the differential value reaches the predetermined value is determined to be the timing at which the subject's physical state changes. Therefore, the physical state detection unit can detect the physical state of the subject based on whether or not the differential value is greater than or equal to a predetermined value. The predetermined value can be set appropriately depending on the type of biological signal used and the type of physical state to be detected.

[0027] For example, when acquiring the sweat lactate concentration as a biosignal from a subject during exercise, the sweat lactate concentration increases with time from the start of acquiring the biosignal (i.e., the subject's exercise time). The timing at which the differential value (rate of change over time) of the sweat lactate concentration first rises above a predetermined value after the start of acquiring the signal can be determined to be the timing at which the subject's metabolism shifts from being predominantly fat-metabolized to predominantly glucose-metabolized. Therefore, the physical state detection unit can detect the subject's physical state as one in which metabolism is predominantly fat-metabolized before the differential value reaches a predetermined value, and after the differential value reaches a predetermined value, it can detect the subject's physical state as one in which metabolism is predominantly glucose-metabolized. On the other hand, the shift in the subject's metabolism from being predominantly glucose-metabolized to being predominantly fat-metabolized can be detected by the sweat lactate concentration itself falling below a specific value (e.g., lactate threshold).

[0028] The physical state detection unit can, if necessary, further calculate the elapsed time from the start of acquiring the biological signal until the differential value reaches a predetermined value, that is, the elapsed time until the differential value rises above the predetermined value. This time corresponds to the elapsed time from the start of acquiring the biological signal until the subject's physical state changes. For example, when acquiring the lactic acid concentration in sweat from a subject during exercise as described above, the duration of the exercise until the subject's physical state shifts to one of glucose metabolism dominance can be calculated based on the elapsed time.

[0029] In the apparatus of the present invention, a computer such as a personal computer (PC), smartphone, or smartwatch can be used as the body state detection unit.

[0030] <Display section> The display unit in the apparatus of the present invention displays information about the subject's physical condition, as well as biosignals and their derivatives acquired by the apparatus of the present invention. Preferably, the display unit displays information about the subject's physical condition along with a graph representing the biosignals and their derivatives. Preferably, the graph represents the change in the biosignals and their derivatives over time. In one embodiment, a graph is displayed that plots the data for the biosignals and their derivatives from the start of acquisition to the latest acquisition against time. In another embodiment, a graph is displayed that plots the data for the latest biosignals and their derivatives over a certain period of time against time.

[0031] In the display unit, information about the subject's physical condition can be displayed in any manner. In one embodiment, the display unit is equipped with a display, and the information about the physical condition is displayed on the display along with a graph representing the biosignal and its differential value. On the display, the information about the physical condition can be displayed in any manner, such as by text such as "fat metabolism mode" (or "aerobic exercise mode"), "glucose metabolism mode" (or "anaerobic exercise mode"), marks such as circles and triangles or their colors, the background color of the display, or the color of the graph representing the biosignal and its differential value. Alternatively, the graph representing the biosignal and its differential value may be displayed on the display, and the information about the physical condition may be represented by an alarm sound or the like.

[0032] The display unit may also display, if necessary, information such as the elapsed time from the start of acquiring the biological signal until the differential value reaches a predetermined value, or the duration of the movement until the differential value reaches a predetermined value.

[0033] In order to avoid initial noise contained in the biological signal, it is preferable that the detection of the physical state by the physical state detection unit or the display by the display unit be suspended for a certain period of time from the start of acquisition of the biological signal by the biological signal detection unit.

[0034] [Device operation] In the apparatus of the present invention, the acquisition of the differential value of the biological signal in the differential circuit unit, the detection of the physical state in the physical state detection unit, and the display of a graph representing the biological signal and the differential value, as well as information about the physical state, are performed in parallel with the sequential acquisition of the biological signal in the biological signal detection unit. The operation of such an apparatus of the present invention may be performed under the control of a control unit. For example, the control unit controls the start and stop of the acquisition of the biological signal in the biological signal detection unit; the sequential reception of data from the biological signal detection unit and the differential circuit unit; the real-time creation of a graph using the received data, the detection of the physical state, and the display of the graph and information about the physical state in the display unit. Preferably, the control unit is composed of one or more computers and may be controlled by a program. The computer can be a personal computer (PC), a smartphone, a smartwatch, etc. The control unit may also be equipped with a hard disk or storage medium that records a program for controlling the operation of the apparatus of the present invention. The computer constituting the control unit and the computer used as the differential circuit unit or physical state detection unit may be the same or different.

[0035] Therefore, the device of the present invention can analyze and display the physical state of a subject or its changes in real time. By providing real-time feedback of the subject's physical state or its changes, it becomes possible to evaluate the subject's current physical state or maintain the physical state in an appropriate or desirable state. For example, by providing real-time feedback of information on the subject's changes in physical state to the subject or their observer during exercise, it becomes possible to adjust or optimize the exercise load on the subject.

[0036] 〔program〕 Preferably, the operation of the apparatus of the present invention is controlled by a program. The program performs the following steps (a) to (c): (a) A process of sequentially acquiring biosignals and their differential values ​​from the subject, (b) A step of detecting the physical state of the subject based on the differential value, (c) A step of displaying a graph representing the biosignal and the differential value, and information about the physical state.

[0037] In step (a), the acquisition of a biological signal from the biological signal detection unit and the acquisition of a differential value from the differential circuit unit are performed sequentially. The acquired biological signal and differential value data are used for detecting the physical state in the physical state detection unit and for displaying the data in the display unit. In step (b), the physical state detection unit performs detection of the physical state based on the differential value. In step (c), the display unit displays the biological signal and differential value data acquired in steps (a) and (b), as well as information about the physical state. Steps (b) and (c) are performed in parallel with step (a). This ensures that the detection of the physical state, as well as the display of graphs representing the biosignals and their derivatives, and information about the physical state, are performed in parallel with the sequential acquisition of the biosignals and their derivatives.

[0038] Hereinafter, exemplary embodiments of the apparatus of the present invention will be described with reference to the drawings.

[0039] Figure 1 is a conceptual diagram of one embodiment of the bioanalysis device of the present invention. In the device shown in Figure 1, the biosignal detection unit is an electrical signal detection unit that detects and outputs electrical signals related to the biosignals of a subject. A differential circuit unit is connected to the output of the electrical signal detection unit. The information processing device comprises a control unit and a display unit. The control unit instructs the electrical signal detection unit to measure the biosignals of the subject. The acquired biosignals are differentiated by the differential circuit unit. The obtained biosignal data and its differential value are transmitted sequentially to the information processing device, and the control unit sequentially displays the transmitted data in a graph on the display unit. Furthermore, the control unit acts as a physical state detection unit that detects the physical state of the subject based on the differential value. The obtained information about the physical state is displayed on the display unit. The operation of the control unit is controlled by the program, and data acquisition and display are performed. In the device shown in Figure 1, the method of instruction and data transmission / reception between the electrical signal detection unit and the differential circuit unit and the information processing device is not limited, but a wireless method is preferred from the viewpoint of the subject's convenience.

[0040] Figure 2 is a conceptual diagram showing one embodiment of the bioanalysis device of the present invention when attached to a subject. The electrical signal detection unit is equipped with an electrochemical sensor and is integrally configured with the differential circuit unit. A smartwatch, smartphone, PC, etc., is used as an information processing device to instruct the measurement of biosignals and their differential values, and to detect the physical state and display the data. The electrical signal detection unit and the differential circuit unit are attached to the upper arm of the subject so that the electrochemical sensor is in contact with the skin. The obtained biosignal and differential value data is transmitted to the information processing device.

[0041] Figure 3 is a flowchart illustrating one embodiment of the operation process of the bioanalytical device of the present invention. When the device starts operating, an electric current is acquired as a biosignal and differentiated with respect to time. The acquired biosignal and its derivative are graphed. If the acquired derivative is less than a predetermined value, the process of acquiring the biosignal and its derivative, and graphing them, is repeated. On the other hand, if the acquired derivative reaches a predetermined value, in addition to graphing the biosignal and its derivative, a message regarding the physical state determined based on the derivative is displayed on the graph. After that, the operation process either ends or is repeated from the acquisition of the biosignal and its derivative.

[0042] As exemplary embodiments of the present invention, the following substances, manufacturing methods, uses, or methods are further disclosed herein. However, the present invention is not limited to these embodiments.

[0043] [1] A bioanalytical device, A biosignal detection unit for sequentially acquiring biosignals from a subject; A differentiation circuit unit for differentiating the biological signal output from the biological signal detection unit and obtaining the differential value of the biological signal; A body state detection unit for detecting the physical state of the subject based on the differential value; and, A graph representing the biosignal and the differential value, and a display unit for displaying information about the physical state. Equipped with, This device performs the acquisition of the differential value of a biological signal in the differential circuit section, the detection of a physical state in the physical state detection section, and the display of a graph representing the biological signal and the differential value, as well as information about the physical state, in parallel with the sequential acquisition of the biological signal in the biological signal detection section. A bioanalytical analyzer. [2] Preferably, the bioanalytical apparatus according to [1], wherein the graph represents the changes in the biosignal and the differential value over time. [3] Preferably, the biological analysis apparatus according to [1] or [2], wherein the physical state detection unit detects the physical state of the subject based on whether the differential value is greater than or equal to a predetermined value. [4] Preferably, the biological analysis apparatus according to [3], wherein the physical state detection unit further calculates the elapsed time from the start of acquisition of the biological signal until the differential value reaches a predetermined value. [5] Preferably, the bioanalytical device according to any one of [1] to [4], wherein the subject is a subject in motion. [6] The biosignal is Preferably, the signal reflects the concentration of substances in the subject's bodily fluids, heart rate, blood O2 concentration, or exhaled CO2 concentration. More preferably, the signal reflects the lactate concentration in the sweat, the lactate concentration in the blood, or the CO2 concentration in the exhaled breath of the subject. More preferably, the signal reflects the lactic acid concentration in the sweat of the subject. A bioanalytical device as described in any one of items [1] to [5]. [7] Preferably, the bioanalytical device according to [6], wherein the information regarding the physical condition indicates that the subject's metabolism is predominantly glucose metabolism or predominantly fat metabolism. [8] Preferably, The subject is a subject in motion, The aforementioned biological signal is the concentration of lactate in sweat. The aforementioned physical state detection unit is After the acquisition of the biosignal begins, and before the differential value of the biosignal reaches a predetermined value, the physical state of the subject is detected as a state in which metabolism is predominantly fat metabolism. After the differential value reaches the predetermined value, the physical state of the subject is detected as a state in which metabolism is predominantly glucose metabolism. [1] The bioanalytical device described in [1]. [9] Preferably, the biosignal detection unit Equipped with an electrochemical sensor, The electrical signal is output to the differential circuit section. The bioanalytical devices described in [1] to [8].

[10] Preferably, the system includes a control unit that controls the start and stop of acquiring biological signals in the biological signal detection unit, the reception of data from the biological signal detection unit and the differential circuit unit, the creation of a graph representing the biological signal and the differential value in real time using the received data, the display of the graph on the display unit, and the detection of the physical state of the subject in the physical state detection unit, and the display of information on the physical state on the display unit. Furthermore, the control unit includes the body state detection unit. The bioanalytical analyzers described in [1] to [9].

[0044]

[11] A program for performing the following steps (a) to (c), (a) A process of sequentially acquiring biosignals and their differential values ​​from the subject, (b) A step of detecting the physical state of the subject based on the differential value, (c) A step of displaying a graph representing the biosignal and the differential value, and information about the physical state. Steps (b) and (c) are performed in parallel with step (a). program.

[12] Preferably, the program according to

[11] , wherein the graph represents the changes in the biological signal and the differential value over time.

[13] Preferably, the program according to

[11] or

[12] , wherein step (b) includes a step of detecting the physical condition of the subject based on whether the differential value is greater than or equal to a predetermined value.

[14] Preferably, the program according to

[13] , wherein step (b) further includes calculating the elapsed time from the start of acquisition of the biological signal until the differential value reaches a predetermined value.

[15] Preferably, the program according to any one of

[11] to

[14] , wherein the subject is a subject in motion.

[16] The biosignal is Preferably, the signal reflects the concentration of substances in the subject's bodily fluids, heart rate, blood O2 concentration, or exhaled CO2 concentration. More preferably, the signal reflects the lactate concentration in the sweat, the lactate concentration in the blood, or the CO2 concentration in the exhaled breath of the subject. More preferably, the signal reflects the lactic acid concentration in the sweat of the subject. A program as described in any one of items

[11] to

[15] .

[17] Preferably, the program according to

[16] , wherein the information regarding the physical condition indicates that the subject's metabolism is predominantly glucose-metabolized or predominantly fat-metabolized.

[0045]

[18] A method for sequentially acquiring biological signals from a subject and displaying information about the biological signals, their differential values, and the physical state of the subject, (a) A process of sequentially acquiring biosignals and their differential values ​​from the subject, (b) A step of detecting the physical state of the subject based on the differential value, (c) A step of displaying a graph representing the biosignal and the differential value, and information about the physical state. Steps (b) and (c) are performed in parallel with step (a), method.

[19] Preferably, the method according to

[18] , wherein the graph represents the changes in the biological signal and the differential value over time.

[20] Preferably, the method according to

[18] or

[19] , wherein step (b) includes a step of detecting the physical condition of the subject based on whether the differential value is greater than or equal to a predetermined value.

[21] Preferably, the method according to

[20] , wherein step (b) further includes calculating the elapsed time from the start of acquisition of the biological signal until the differential value reaches a predetermined value.

[22] Preferably, the method according to any one of

[18] to

[21] , wherein the subject is a subject in motion.

[23] The biosignal is Preferably, the signal reflects the concentration of substances in the subject's bodily fluids, heart rate, blood O2 concentration, or exhaled CO2 concentration. More preferably, the signal reflects the lactate concentration in the sweat, the lactate concentration in the blood, or the CO2 concentration in the exhaled breath of the subject. More preferably, the signal reflects the lactic acid concentration in the sweat of the subject. The method described in any one of items

[18] to

[22] .

[24] Preferably, the information regarding the physical condition indicates that the subject's metabolism is predominantly glucose metabolism or predominantly fat metabolism, according to the method of

[23] .

[25] Preferably, The subject is a subject in motion, The aforementioned biological signal is the concentration of lactate in sweat. The above step (b) is as follows: After the start of acquiring the biosignal, and before the differential value of the biosignal reaches a predetermined value, the physical state of the subject is detected as a state in which metabolism is predominantly fat metabolism; and, After the differential value reaches the predetermined value, the physical state of the subject is detected as a state in which metabolism is predominantly glucose metabolism. including,

[18] The method described.

[0046]

[26] Information processing device, It comprises a control unit and a display unit, The control unit is Sequential reception of biosignals and their differential values ​​from the subject, Using the received data, create a graph in real time representing the biosignal and its differential value, detect the subject's physical condition based on the differential value, and display the graph and information about the physical condition on the display unit. Control, The display unit displays a graph showing the changes over time in the subject's biological signals and their differential values, and information about the subject's physical condition. Information processing device.

[27] Preferably, the apparatus according to

[26] , wherein the detection of the physical state of the subject is based on whether or not the differential value is greater than or equal to a predetermined value.

[28] Preferably, the apparatus according to

[26] or

[27] , wherein the subject is a subject in motion.

[29] The biosignal is, Preferably, the signal reflects the concentration of substances in the subject's bodily fluids, heart rate, blood O2 concentration, or exhaled CO2 concentration. More preferably, the signal reflects the lactate concentration in the sweat, the lactate concentration in the blood, or the CO2 concentration in the exhaled breath of the subject. More preferably, the signal reflects the lactic acid concentration in the sweat of the subject. The apparatus described in any one of items

[26] to

[28] .

[30] Preferably, the apparatus according to

[29] , wherein the information regarding the physical condition indicates that the subject's metabolism is predominantly glucose metabolism or predominantly fat metabolism.

[31] Preferably, The subject is a subject in motion, The aforementioned biological signal is the concentration of lactate in sweat. The detection of the subject's physical state includes detecting the subject's physical state as a state in which metabolism is predominantly fat metabolism before the differential value of the biological signal reaches a predetermined value, and detecting the subject's physical state as a state in which metabolism is predominantly glucose metabolism after the differential value reaches the predetermined value. The apparatus described in

[26] . [Examples]

[0047] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0048] (Electrode fabrication) [Working electrode] Washi paper (Shoun, a type of Japanese paper manufactured by Hanshiya) was prepared as the base material. Carbon paste (JELCON, CH-8, manufactured by Jujo Chemical Co., Ltd.) was applied to one side of the washi paper and baked at 120°C for 15 minutes. This process of applying and baking the carbon paste was repeated six times, creating a total of six carbon layers to form the lead section. Next, 0.75 g of porous carbon Knobel (manufactured by Toyo Tanso Co., Ltd.) was mixed with 2.6 mL of N-methyl-2-pyrrolidone (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) and 7.6 mL of PVDF resin (manufactured by Kureha Corporation, KF Polymer; L#9305) to prepare a paste containing porous carbon Knobel. The prepared paste was applied to the lead portion described above and baked at 60°C for 24 hours. The application and baking of the paste was repeated three times to create a total of three porous carbon layers. In this way, an electrode containing a porous carbon layer, a lead layer, and a substrate was fabricated. Thionine acetate (manufactured by Tokyo Chemical Industry Co., Ltd.) was dissolved in methanol to obtain a 50 mM thionine acetate methanol solution. L-lactate oxidase (manufactured by Toyobo Co., Ltd.; LCO301) was dissolved in 0.1 M PBS solution (pH 7.4) to obtain an L-lactate oxidase solution. 20 μL of the above thionine acetate solution was applied to the porous carbon layer of the electrode, dried under reduced pressure at room temperature for 90 minutes, and then 20 μL of the L-lactate oxidase solution (enzyme amount 40 U) was applied. In this way, a working electrode with the mediator and enzyme immobilized was prepared.

[0049] [Counter electrode (reference electrode)] Similar to the procedure for creating the working electrode described above, a lead layer consisting of six carbon layers was formed on one side of the base material (Japanese paper), and then three porous carbon layers were formed to create the electrode. Bilbyrin oxidase (manufactured by Amano Enzyme Co., Ltd.; WAK-AMA-BO3) was dissolved in a 0.1 M PBS solution (pH 7.4) to obtain a bilirubyrin oxidase solution. 20 μL (enzyme amount 2.5 U) of this solution was applied to the porous carbon layer of the electrode to prepare a counter electrode.

[0050] (Example 1) [Measurement System] A measurement system including an electrochemical sensor equipped with the electrodes fabricated as described above was constructed as shown in Figure 4. An electrochemical sensor was constructed with the counter electrode at ground potential and the working electrode providing a current output. The potential of the working electrode was amplified by a non-inverting amplifier circuit. The time derivative of the sensor output was obtained as a voltage signal using a differentiating circuit.

[0051] [Measurement and display of lactic acid concentration] The lactic acid concentration in the solution was measured using the measurement system shown in Figure 4. The working electrode and counter electrode of the electrochemical sensor were immersed in 50 mL of PBS solution (the solution to be measured). The solution to be measured was stirred at 500 rpm using a stirring bar. After confirming that the background current had stabilized at 20 μA, 1 M lactic acid solution was added sequentially. After 170 seconds, 0.5 mL of 1 M lactic acid solution was added to the stirring PBS solution in 1 second to adjust the lactic acid concentration in the solution to 9.9 mM. Subsequently, 1.0 mL, 1.5 mL, and 2.0 mL of lactic acid solution were added in 1 second at 40 seconds, 150 seconds, and 280 seconds after the initial addition of the lactic acid solution, respectively, to sequentially increase the lactic acid concentration in the solution to 29.1 mM, 56.6 mM, and 90.9 mM.

[0052] During the above procedure, the output of the electrochemical sensor and its time derivative were digitally converted by a wireless device (BLE wireless module IMBLE2; manufactured by Interplan Corporation) and wirelessly transmitted to an information processing device (PC) (transmission interval 1 second). The PC that received the data displayed the received data on its screen in real time and created a graph showing the change in the received data over time. The measurement of data by the electrochemical sensor and the reception and display of data by the PC were controlled by a program on the PC. A graph was obtained plotting the current (μA) and its time derivative (A / s) against time (s), as shown in Figure 5. Furthermore, as shown in Figure 6, the measured time derivative (A / s) showed a high linear correlation (coefficient of determination R) with the rate of change of lactic acid concentration in the solution (mM / s). 2 There was a value of 0.9963.

[0053] (Example 2) Using the data obtained in Example 1, we attempted to sequentially detect and display the metabolic mode. Specifically, the current (μA) and its time derivative (A / s) obtained in Example 1 were sequentially displayed on a graph in the order in which they were acquired. Based on this time derivative, the metabolic mode was detected and displayed on the graph. The rate of change in lactate concentration at the transition point of the metabolic mode differs among subjects, but as a model case, 17 (mM / s) was set as the threshold (predetermined value) for the rate of change in lactate concentration corresponding to the transition point of the metabolic mode. From the linear correlation equation described above based on Figure 6, in the measurement system of Example 1, the time derivative of the current corresponding to the threshold for the rate of change in lactate concentration was 0.01 (A / s). Therefore, when a time derivative of the current of 0.01 A / s or more was not acquired after the start of data measurement, the body was evaluated as being predominantly in a fatty metabolism state, and the message "fat metabolism mode" (or "aerobic exercise mode") was displayed in the upper left corner of the graph (Figure 7). Subsequently, after obtaining a time derivative value of 0.01 A / s or higher, the body was evaluated as being predominantly glucose-metabolized, and the message "glucose metabolism mode" (or "anaerobic exercise mode") was displayed in the upper left corner of the graph (Figure 8).

Claims

1. A bioanalytical device, A biosignal detection unit for sequentially acquiring biosignals from a subject; A differentiation circuit unit for differentiating the biological signal output from the biological signal detection unit and obtaining the differential value of the biological signal; A body state detection unit for detecting the physical state of the subject based on the differential value; and, A graph representing the biosignal and the differential value, and a display unit for displaying information about the physical state. Equipped with, This device performs the acquisition of the differential value of a biological signal in the differential circuit section, the detection of a physical state in the physical state detection section, and the display of a graph representing the biological signal and the differential value, as well as information about the physical state, in parallel with the sequential acquisition of the biological signal in the biological signal detection section. A bioanalytical analyzer.

2. The bioanalytical device according to claim 1, wherein the graph represents the changes in the biosignal and the differential value over time.

3. The biological analysis apparatus according to claim 1, wherein the physical condition detection unit detects the physical condition of the subject based on whether or not the differential value is greater than or equal to a predetermined value.

4. The bioanalytical device according to claim 3, wherein the physical state detection unit further calculates the elapsed time from the start of acquisition of the biological signal until the differential value reaches a predetermined value.

5. The bioanalytical device according to claim 1, wherein the subject is a subject in exercise.

6. The bioanalytical device according to claim 1, wherein the biosignal is a signal that reflects the lactic acid concentration in the sweat of the subject.

7. The bioanalytical device according to claim 6, wherein the information regarding the physical condition indicates that the subject's metabolism is predominantly glucose metabolism or predominantly fat metabolism.

8. A program for executing the following steps (a) to (c), (a) A process of sequentially acquiring biological signals and their differential values ​​from the subject, (b) A step of detecting the physical state of the subject based on the differential value, (c) A step of displaying a graph representing the biosignal and the differential value, and information about the physical state. Steps (b) and (c) are performed in parallel with step (a). program.

9. The program according to claim 8, wherein the graph represents the changes in the biological signal and the differential value over time.

10. The program according to claim 8, wherein step (b) includes a step of detecting the physical condition of the subject based on whether the differential value is greater than or equal to a predetermined value.

11. The program according to claim 10, wherein step (b) further includes calculating the elapsed time from the start of acquiring the biological signal until the differential value reaches a predetermined value.

12. The program according to claim 8, wherein the subject is a subject in motion.

13. The program according to claim 8, wherein the biosignal is a signal that reflects the lactic acid concentration in the sweat of the subject.

14. The program according to claim 13, wherein the information regarding the physical condition indicates that the subject's metabolism is predominantly glucose metabolism or predominantly fat metabolism.

15. A method for sequentially acquiring biological signals from a subject and displaying the biological signals, their differential values, and information about the subject's physical condition, (a) A process of sequentially acquiring biological signals and their differential values ​​from the subject, (b) A step of detecting the physical state of the subject based on the differential value, (c) A step of displaying a graph representing the biosignal and the differential value, and information about the physical state. Steps (b) and (c) are performed in parallel with step (a), method.

16. An information processing device, It comprises a control unit and a display unit, The control unit is Sequential reception of biosignals and their differential values ​​from the subject, Using the received data, create a graph in real time representing the biosignal and its differential value, detect the subject's physical condition based on the differential value, and display the graph and information about the physical condition on the display unit. Control, The display unit displays a graph showing the changes over time in the subject's biological signals and their differential values, and information about the subject's physical condition. Information processing device.

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