Biological component measurement device and biological component measurement method

Abstract

The excitation light source (1) emits excitation light that advances in the optical medium (3) toward the sample (5) placed on the sample placement surface. The probe light source (2) emits probe light advancing in the optical medium (3). The light position detector (4) detects the position of the emitted probe light emitted from the optical medium (3). The arithmetic unit (11) calculates the position of the probe light emitted by the light position detector (4) when the sample (5) is a reference substance that absorbs the excitation light and does not have a specific absorption peak within the excitation wavelength of the excitation light, and the position of the probe light emitted by the light position detector (4) when the sample (5) is a biological substance. The amount or concentration of the biological component in the biological substance is calculated.

Description

Technical Field

[0001] This disclosure relates to an apparatus for measuring the composition of organisms and a method for measuring the composition of organisms. Background Technology

[0002] Previously, apparatus and methods for measuring biological components were known. For example, the method described in Japanese Patent Application Publication No. 2017-519214 (Patent Document 1) includes: a step of placing an optical medium on the surface of a substance, such that at least one region of the surface of the optical medium is in contact with the surface of the substance; a step of irradiating the surface of the substance with an excitation beam having an excitation wavelength through a region of the surface of the optical medium in contact with the surface of the substance; a step of emitting a probe beam through the optical medium onto the surface region of the optical medium in direct contact with the surface of the substance, wherein the probe beam is emitted in such a way that the probe beam and the excitation beam are repeated at the boundary between the optical medium and the surface of the substance, and the probe beam is reflected at the boundary; a step of directly or indirectly detecting the deflection of the reflected probe beam corresponding to the wavelength of the excitation beam; and a step of analyzing the substance based on the deflection of the reflected probe beam depending on the wavelength of the emitted beam.

[0003] Existing technical documents

[0004] Patent documents

[0005] Patent Document 1: Japanese Patent Publication No. 2017-519214 Summary of the Invention

[0006] In the device disclosed in Patent Document 1, an infrared light source is used to emit an excitation beam. The infrared light source is affected by external factors such as heat accumulation inside the source or changes in external temperature, resulting in unstable infrared light output. Consequently, the heating of biological substances caused by infrared light irradiation also varies, leading to unstable accuracy in measuring the quantity or concentration of biological components.

[0007] Therefore, the purpose of this disclosure is to provide a biological component measuring device and a biological component measuring method that are not affected by the instability of infrared light and can accurately measure the amount or concentration of biological components.

[0008] This disclosure provides a biological component determination device, comprising: an optical medium including a sample mounting surface; an excitation light source emitting excitation light that propagates through the optical medium and has the excitation wavelength of the sample toward a sample mounted on the sample mounting surface; a probe light source emitting probe light that propagates through the optical medium; a photodetector detecting the position of the emitted probe light emitted from the optical medium; and a calculator calculating the amount or concentration of biological components in the biological substance based on the position of the emitted probe light detected by the photodetector when the sample is a reference material and the position of the emitted probe light detected by the photodetector when the sample is a biological substance. The reference material absorbs the excitation light and has no specific absorption peak within the excitation wavelength of the excitation light.

[0009] This disclosure provides a method for determining the composition of a biological substance, comprising: emitting excitation light, having the excitation wavelength of the sample, into the optical medium via an excitation light source that propagates through the optical medium; emitting probe light, having the excitation wavelength of the sample, via a probe light source; detecting the position of the emitted probe light incident on the optical medium when the sample is a reference substance using a photodetector; detecting the position of the emitted probe light incident on the optical medium when the sample is a biological substance using a photodetector; and calculating the amount or concentration of the biological component in the biological substance based on the positions of the emitted probe light detected by the photodetector when the sample is a reference substance and when the sample is a biological substance using a photodetector. The reference substance absorbs the excitation light and does not exhibit a specific absorption peak within the excitation wavelength of the excitation light.

[0010] According to this disclosure, the amount or concentration of biological components in biological substances is calculated based on the position of the emitted probe light detected by the light position detector when the sample is a reference material and the position of the emitted probe light detected by the light position detector when the sample is a biological substance. Therefore, it is not affected by the instability of infrared light and can accurately determine the amount or concentration of biological components. Attached Figure Description

[0011] Figure 1 This is a diagram showing the structure of the biological composition measuring device according to Embodiment 1.

[0012] Figure 2 (a) and (b) are diagrams showing the optical path of the probe light 7.

[0013] Figure 3 This is a flowchart illustrating the process of measuring the biological components using the biological component measuring device in Embodiment 1.

[0014] Figure 4This is a diagram showing the structure of a biological composition analysis device according to a variation of Embodiment 1.

[0015] Figure 5 This is a flowchart illustrating the process of measuring the biological components using the biological component measuring device of Embodiment 2.

[0016] Figure 6 This is a diagram showing the structure of the arithmetic unit 11.

[0017] Figure 7 This is a diagram showing the structure of the learning device 91 according to Embodiment 3.

[0018] Figure 8 This is a diagram showing the structure of the inference device 95 according to Embodiment 3.

[0019] Figure 9 This is a diagram showing the structure of the learning device 91A according to Embodiment 4.

[0020] Figure 10 This is a diagram showing the structure of the inference device 95A according to Embodiment 4.

[0021] Figure 11 This is a diagram showing the structure of the learning device 91B according to Embodiment 5.

[0022] Figure 12 This is a diagram showing the structure of the inference device 95B according to Embodiment 5.

[0023] Figure 13 This is a diagram showing the structure of the learning device 91C according to Embodiment 6.

[0024] Figure 14 This is a diagram showing the structure of the inference device 95C according to Embodiment 6.

[0025] Figure 15 This is a diagram showing the structure when the functions of the arithmetic unit 11 are implemented using software. Detailed Implementation

[0026] Implementation method 1.

[0027] Figure 1 This is a diagram showing the structure of the biological composition measuring device according to Embodiment 1. The biological composition measuring device includes an excitation light source 1, a detection light source 2, an optical medium 3, a light position detector 4, and a processing unit 11.

[0028] Excitation source 1 has at least one infrared light source. Excitation source 1 includes a broadband quantum cascade laser that emits infrared light in all wavelength domains, or a portion thereof, including the excitation wavelength (wavelength of the fingerprint spectrum) of the component to be measured in sample 5. If the component to be measured is sugar in the human body, the wavelengths used in the measurement will be, for example, λ1, λ2, and λ3. Wavelengths λ1 and λ2 are the excitation wavelengths of sugar in the human body and are absorbed by sugar in the human body. The light at wavelength λ3 is used as a reference wavelength that is not absorbed by sugar in the human body but is absorbed by the reference substance. Four or more wavelengths can also be used in the measurement.

[0029] Infrared light emitted from the excitation source 1 is used as excitation light 6 and is transmitted through the optical medium 3 to the sample 5. When measuring the components contained in a living organism, the excitation light 6 is incident on the skin of the organism's fingers, arms, ears, etc., and the absorption of light by substances contained inside the organism, such as substances contained in interstitial fluid, is measured.

[0030] The probe light source 2 emits probe light 7. Probe light 7 is incident on the optical medium 3 from the third surface 33. Probe light 7 is refracted at the third surface 33 and propagates in the optical medium 3 toward the interface between the optical medium 3 (second surface 32) and the sample 5.

[0031] Figure 2 (a) and (b) are diagrams showing the optical path of the probe light 7.

[0032] When viewed from above the sample mounting surface (second surface 32), the optical path of the probe light 7 in the optical medium 3 is part of the portion of the sample mounting surface (second surface 32) irradiated by the excited light 6. Figure 2 (a) or all ( Figure 2 (b) overlap.

[0033] The probe light 7 is internally totally internally reflected at the interface between the optical medium 3 (second surface 32) and the sample 5. During its propagation within the optical medium 3, the probe light 7 travels through a refractive index gradient region 8 generated within the optical medium 3 due to the heat absorbed by the sample 5. The probe light 7 is refracted in the refractive index gradient region 8, causing a change in its direction of travel. The probe light 7 exits from the fourth surface 34 of the optical medium 3.

[0034] The wavelength of the light output from the probe light source 2 can be any wavelength band as long as it is within the wavelength band of the transmission optical medium 3. For example, the visible light region of 400-900nm, which is mass-produced and inexpensive for many applications, or the invisible region of 1300-1700nm used in optical fiber communication, can be used.

[0035] The optical medium 3 is composed of a material through which the excitation light 6 emitted from the excitation source 1 and the incident probe light 7 emitted from the probe source 2 are transmitted. For example, the optical medium 3 is generally composed of substances such as zinc sulfide (ZnS) or zinc selenide (ZnSe), which have high transmittance in the wavelength region of visible light to infrared light. When the measurement object is a biological sample, zinc sulfide (ZnS) can be used as the optical medium 3 considering biological stability. Alternatively, a chalcogenide glass with a lower thermal conductivity than zinc sulfide (ZnS) or zinc selenide (ZnSe) can be used in a way that makes the change in the refractive index of the optical medium 3 caused by heat occurring in the sample 5 localized.

[0036] This describes the case where the light output of excitation source 1 is zero (reference state). In the reference state, the internal state of optical medium 3 is uniform, so the light output from probe source 2 is refracted only during incident and emission within optical medium 3. In the reference state, the position where the emitted probe light 7a is incident on the light position detector 4 is set as the reference position RP. In this embodiment, the path of probe light 7a is shown as a path that undergoes total internal reflection once at the interface between optical medium 3 and sample 5. However, any path that passes through the refractive index gradient region 8 occurring in optical medium 3 is acceptable, or it could be a path that undergoes total internal reflection twice or more within the optical medium, or a path that passes parallel to the contact surface near the contact surface with sample 5.

[0037] Next, the output from excitation source 1 will be described. Excitation source 1 outputs infrared light of the fingerprint spectrum wavelength of the component in sample 5 to be measured as excitation light 6. Excitation light 6 is incident on sample 5 via optical medium 3. Excitation light 6 is absorbed by sample 5. Absorption heat occurs in sample 5 due to absorption. The absorbed heat is transferred to optical medium 3, generating a temperature gradient inside optical medium 3. The refractive index of optical medium is generally temperature-dependent, so a refractive index gradient region 8 is formed according to the temperature gradient. This state is defined as the changing state.

[0038] In the changing state, the incident probe light 7 output from the probe light source 2 passes through the refractive index gradient region 8. The incident probe light 7 is refracted according to the tilt of the refractive index at the position where it passes through the refractive index gradient region 8. The refracted incident probe light 7 is emitted from the optical medium 3 as the emitted probe light 7b and incident on the light position detector 4. In the changing state, the position where the emitted probe light 7b incident on the light position detector 4 is set as CP. Figure 1 The image shows the incident position only in the height direction, but the incident position is also displaced in the horizontal direction. The incident positions of the excitation light 6 and the incident probe light 7 are adjusted so that the difference between the reference position RP and the position CP is the maximum, that is, the position where the refractive index gradient is the maximum.

[0039] When the amount of the desired component to be measured in sample 5 (i.e., the component with a high absorption coefficient at a certain wavelength of light emitted from excitation source 1) is high, the amount of light absorbed in sample 5 increases, resulting in greater heat generation. Consequently, the refractive index gradient increases. The difference between the reference position RP of the emitted probe light 7a incident on the optical position detector 4 under the reference state and the position CP of the emitted probe light 7b incident on the optical position detector 4 under the changing state, and the amount of the desired component to be measured in sample 5, becomes approximately proportional.

[0040] Excitation source 1 originally had an output determined for each wavelength.

[0041] However, the excitation source 1 is affected by external factors such as heat accumulation inside the excitation source 1 and changes in external temperature. In the determination of biological substances, the position CP of the emitted probe light 7b is influenced by external factors. In this embodiment, an absorption spectrophotometry based on a reference substance is used to determine the output reflecting the influence of these external factors. The absorption spectrophotometry uses the light absorption capacity (absorption coefficient) of a substance for light of a certain wavelength, so a substance with a certain absorption coefficient (without a specific absorption peak) in the wavelength band of the excitation source 1 is suitable as a reference substance. The determination of sample 5 using such a reference substance is equivalent to the determination of the output of the excitation light corresponding to the absorption coefficient of the substance.

[0042] In this embodiment, not only is the position CP(B) of the emitted probe light 7b(B) when the biological substance is used as sample 5, but also the position CP(A) of the emitted probe light 7b(A) when the reference substance is used as sample 5 is used to remove the influence of external factors. The position CP(A) becomes an evaluation index for the stability of the light output of the excitation light 6 during measurement. By detecting the position CP(A) when sample 5 is used as reference substance before measuring the amount or concentration of biological components in the biological substance, it is possible to perform a measurement that removes the influence of external factors of the excitation light source 1. As the reference substance, a substance that absorbs the wavelength band of the excitation light source 1 and has no specific absorption peak in that wavelength band, and is in close contact with the optical medium 3, is selected. For example, in the case of the infrared region, water can be cited. The refractive index gradient formed when the reference substance is sample 5 is substantially different from the refractive index gradient formed when the biological substance is sample 5.

[0043] The arithmetic unit 11 calculates the output from the light position detector 4. Based on the position CP(A) of the emitted probe light 7b detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b detected by the light position detector 4 when sample 5 is a biological material, the arithmetic unit 11 determines the amount or concentration of biological components (such as sugars) within the biological material. For example, the arithmetic unit 11 calculates CP(B) - CP(A), or CP(B) / CP(A), as the amount or concentration of components of the biological material (e.g., sugars in the skin).

[0044] Figure 3 This is a flowchart illustrating the process of measuring the biological components using the biological component measuring device in Embodiment 1.

[0045] In step S101, sample 5 is set as a reference substance (e.g., water).

[0046] In step S102, under the changing state of the excitation light 6 illuminating the sample 5 from the excitation light source 1, the light position detector 4 detects the position CP (A) of the emitted probe light 7b (A).

[0047] In step S103, sample 5 is set as a biological substance (e.g., skin).

[0048] In step S104, under the changing state of the excitation light 6 illuminating the sample 5 from the excitation light source 1, the light position detector 4 detects the position CP (B) of the emitted probe light 7b (B).

[0049] In step S105, the arithmetic unit 11 calculates the amount or concentration of a biological substance (e.g., sugar in the skin) based on position CP(A) and position CP(B). For example, the arithmetic unit 11 calculates CP(B)-CP(A) or CP(B) / CP(A) as the amount or concentration of a biological substance (e.g., sugar in the skin).

[0050] According to this embodiment, by using the measurement results when the reference substance is used as sample 5, the output of excitation light affected by external factors can be monitored without adding new constituent elements. By performing group measurements of the reference substance and biological substances, the instability of the excitation light can be eliminated, thus enabling high-precision measurement of the amount or concentration of biological components.

[0051] Alternatively, the difference between position CP(A) and reference position RP can be used instead of position CP(A), and the difference between position CP(B) and reference position RP can be used instead of position CP(B).

[0052] A variation of implementation method 1.

[0053] Figure 4 This is a diagram showing the structure of a biological composition analysis device according to a modified embodiment 1. The biological composition analysis device according to the modified embodiment 1 differs from the non-invasive composition analysis device according to embodiment 1 in that the biological composition analysis device according to the modified embodiment 1 has an optical chopper 20 between the excitation light source 1 and the optical medium 3, and a lock-in amplifier 21 between the optical position detector 4 and the arithmetic unit 11.

[0054] An optical chopper 20 is disposed in the optical path of the excitation light 6. The optical chopper 20 chops the excitation light 6 (continuous light) emitted from the excitation source 1 at an arbitrary frequency. The excitation light 6 becomes intermittent light (pulsed light) that is periodically switched on and off according to the chopping frequency (frequency that turns the light on / off) of the optical chopper 20, and is incident on the optical medium 3. As the optical chopper 20, a known structure can be used. The optical chopper 20, for example, has a rotating disc with an opening that allows the excitation light 6 to pass through and a light-shielding part that blocks the excitation light 6 arranged in the circumferential direction, and a motor that rotates the rotating disc. By using the motor to rotate the rotating disc periodically, it is possible to switch whether the sample 5 is irradiated with the excitation light 6. That is, the excitation light 6 is intensity modulated at the chopping frequency of the optical chopper 20. The chopping frequency of the excitation light 6 is determined by the rotation speed of the rotating disc.

[0055] Optical chopper 20 and lock-in amplifier 21 are connected to an oscillator (not shown). The oscillator sets the chopping frequency (modulation frequency) of optical chopper 20. The oscillator generates a control signal for chopping control of excitation light 6, and provides the generated control signal to optical chopper 20 and lock-in amplifier 21. This control signal contains the chopping frequency of optical chopper 20.

[0056] Lock-in amplifier 21 selectively amplifies the signal from the optical position detector 4 that relates to the position of the probe light 7 and is synchronized with the chopping frequency (modulation frequency) of the optical chopper 20. The on-time of the chopping cycle corresponds to the time during which the excitation light 6 is irradiated. The off-time of the chopping cycle corresponds to the time during which the excitation light 6 is not irradiated.

[0057] Implementation method 2.

[0058] Consider situations where the biological substance being measured is composed of multiple biological components, and the goal is to determine the amount or concentration of one of these components. For example, in the case of human skin, the excitation light is absorbed by multiple components within the skin, such as sugars, oils, and sweat, making it difficult to determine the amount or concentration of a single biological component by measuring only the skin.

[0059] A reference material is selected that is in close contact with the optical medium 3, and has an absorption peak of one or more biological components within that wavelength band, absorbing the wavelength band of the excitation light source 1. For example, sebum deposits or sweat itself on the surface of a biological organism can be used as the reference material. By using the measurement results with the reference material as sample 5, the contribution of biological components other than the desired biological component can be removed. The refractive index gradient formed when the reference material is sample 5 is substantially different from the refractive index gradient formed when the biological material is sample 5.

[0060] Figure 5 This is a flowchart illustrating the process of measuring the biological components using the biological component measuring device of Embodiment 2.

[0061] In step S201, sample 5 is set as a reference substance (e.g., water).

[0062] In step S202, under the changing state of the excitation light 6 illuminating the sample 5 from the excitation light source 1, the light position detector 4 detects the position CP (A) of the emitted probe light 7b (A).

[0063] In step S203, sample 5 is set as a reference material (e.g., sebum deposits or sweat on the surface of an organism).

[0064] In step S204, under the changing state of the excitation light 6 illuminating the sample 5 from the excitation light source 1, the light position detector 4 detects the position CP (C) of the emitted probe light 7b (C).

[0065] In step S205, sample 5 is set as a biological substance (e.g., skin).

[0066] In step S206, under the changing state of the excitation light 6 illuminating the sample 5 from the excitation light source 1, the light position detector 4 detects the position CP (B) of the emitted probe light 7b (B).

[0067] In step S207, the arithmetic unit 11 calculates the amount or concentration of a biological substance (e.g., sugar in the skin) based on position CP(A), position CP(B), and position CP(C). For example, the arithmetic unit 11 calculates CP(B) - CP(A) - CP(C) as the amount or concentration of a biological substance (e.g., sugar in the skin).

[0068] Alternatively, the difference between position CP(A) and reference position RP can be used instead of position CP(A), the difference between position CP(B) and reference position RP can be used instead of position CP(B), and the difference between position CP(C) and reference position RP can be used instead of position CP(C).

[0069] Implementation method 3.

[0070] In Embodiment 1, it is shown that by performing measurements in groups when a reference substance is used as sample 5 and when biological material is used as sample 5, the amount or concentration of biological components within the biological material can be determined based on removing the influence of external factors of the excitation light source 1. In this embodiment, by using the detected CP(A) and CP(B), the amount or concentration of components of the biological material (e.g., sugars in the skin) can be calculated with higher precision.

[0071] Figure 6 This is a diagram showing the structure of the arithmetic unit 11.

[0072] The arithmetic unit 11 includes a learning device 91, an inference device 95, and a learned model storage device 94.

[0073] Figure 7 This is a diagram showing the structure of the learning device 91 according to Embodiment 3.

[0074] The learning device 91 includes a data acquisition unit 92 and a model generation unit 93.

[0075] The data acquisition unit 92 acquires learning data including the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference substance, the position CP(B) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a biological substance, and the amount or concentration BA of the biological component. The learning data is data that correlates the position CP(A) and the position CP(B) of the emitted probe light 7b(A) with the amount or concentration (correct answer) BA of the biological component.

[0076] The model generation unit 93 uses the learning data to generate a learned model for inferring the amount or concentration BA of biological components based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material.

[0077] The learning device 91 and the inference device 95 are not limited to the example of being built into the arithmetic unit 11. For example, the learning device 91 and the inference device 95 may also be an example of being connected to a biological composition measuring device via a network. The learning device 91 and the inference device 95 may also exist on a cloud server.

[0078] The learning algorithm used by the model generation unit 93 can employ well-known algorithms such as supervised learning, unsupervised learning, or reinforcement learning. As an example, the application of a neural network will be illustrated.

[0079] The model generation unit 93 performs so-called supervised learning, for example, based on a neural network model. Here, supervised learning refers to a method of learning features present in the learning data by providing a set of input and result (label) data to a learning device, and inferring the result based on the input. The neural network consists of an input layer composed of multiple neurons, an intermediate layer (hidden layer) composed of multiple neurons, and an output layer composed of multiple neurons. The intermediate layer can be one layer or two or more layers. For example, in a three-layer neural network, when multiple inputs are input to the input layer, their values ​​are multiplied by weight W1 before being input to the intermediate layer, and the result is further multiplied by weight W2 before being output from the output layer. The output result varies depending on the values ​​of weights W1 and W2. The neural network performs so-called supervised learning based on the learning data acquired by the data acquisition unit 92. That is, the neural network learns by inputting the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference substance and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological substance, and by adjusting the weights W1 and W2 in a way that makes the result output from the output layer close to the amount or concentration BA of the biological component (positive solution).

[0080] The model generation unit 93 generates and outputs the learned model by performing the learning process described above.

[0081] The learned model storage device 94 stores the learned model output from the model generation unit 93.

[0082] Figure 8 This is a diagram showing the structure of the inference device 95 according to Embodiment 3. The inference device 95 includes a data acquisition unit 96 and an inference unit 97.

[0083] The data acquisition unit 96 acquires the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when the sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when the sample 5 is a biological material.

[0084] The inference unit 97 uses a learned model stored in the learned model storage device 94, which is used to infer the amount or concentration BA of the biological component based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when the sample 5 is a reference material and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when the sample 5 is a biological material. The inference unit 97 infers the amount or concentration BA of the biological component based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when the sample 5 is a reference material and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when the sample 5 is a biological material, obtained by the data acquisition unit 96.

[0085] In this embodiment, the inference unit 97 uses a learned model learned by the model generation unit 93, but a learned model generated outside the biological composition measuring device may also be used.

[0086] In this embodiment, supervised learning is described as being applied in the learning algorithm used by the model generation unit 93, but it is not limited to this. Regarding the learning algorithm, reinforcement learning, unsupervised learning, or semi-supervised learning can also be applied, in addition to supervised learning.

[0087] The learning algorithm used in the model generation unit 93 can be either deep learning, which extracts the learning features themselves, or machine learning, which can be performed according to other known methods, such as genetic programming, functional logic programming, support vector machines, etc.

[0088] According to this embodiment, it is possible to measure the amount or concentration of a biological component that is to be measured with high precision.

[0089] Implementation method 4.

[0090] In this embodiment, the arithmetic unit 11 includes a learning device 91A, an inference device 95A, and a learned model storage device 94A.

[0091] Figure 9 This is a diagram showing the structure of the learning device 91A according to Embodiment 4. The learning device 91A includes a data acquisition unit 92A and a model generation unit 93A.

[0092] The data acquisition unit 92A acquires learning data including the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material, and the amount or concentration BA of the biological component.

[0093] The model generation unit 93A uses the learning data to generate a learned model for inferring the amount or concentration BA of biological components based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material.

[0094] The learned model storage device 94A stores the learned model output from the model generation unit 93A.

[0095] Figure 10 This is a diagram showing the structure of the inference device 95A according to Embodiment 4. The inference device 95A includes a data acquisition unit 96A and an inference unit 97A.

[0096] The data acquisition unit 96A acquires the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material.

[0097] The inference unit 97A uses a learned model stored in the learned model storage device 94A, which infers the amount or concentration BA of the biological component based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material. The inference unit 97A infers the amount or concentration BA of the biological component based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material, acquired by the data acquisition unit 96A.

[0098] According to this embodiment, it is possible to measure the amount or concentration of a biological component that is to be measured with high precision.

[0099] Implementation method 5.

[0100] The arithmetic unit 11 in embodiment 5 includes a learning device 91B, an inference device 95B, and a learned model storage device 94B.

[0101] Figure 11 This diagram illustrates the structure of the learning device 91B according to Embodiment 5. The learning device 91B includes a data acquisition unit 92B, a preprocessing unit 98B, and a model generation unit 93B.

[0102] The data acquisition unit 92B acquires data including the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference substance, the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological substance, and the amount or concentration BA of the biological component.

[0103] The preprocessing unit 98B calculates an index α based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material. Index α is data that makes the biological components significant. Index α can be set, for example, as CP(B)-CP(A) or CP(B) / CP(A). The preprocessing unit 98B can reduce the amount of data and time related to learning, and can avoid overlearning.

[0104] The model generation unit 93B uses learning data, including index α and the amount or concentration BA of biological components, to generate a learned model for inferring the amount or concentration BA of biological components based on index α.

[0105] The learned model storage device 94B stores the learned model output from the model generation unit 93B.

[0106] Figure 12 This is a diagram showing the structure of the inference device 95B according to Embodiment 5. The inference device 95B includes a data acquisition unit 96B, a preprocessing unit 99B, and an inference unit 97B.

[0107] The data acquisition unit 96B acquires the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material.

[0108] The preprocessing unit 99B calculates an index α based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material.

[0109] The inference unit 97B uses the learned model stored in the learned model storage device 94B, which is used to infer the amount or concentration BA of the organism component based on the index α, to infer the amount or concentration BA of the organism component based on the index α calculated by the preprocessing unit 99B.

[0110] According to this embodiment, the amount of data and time related to learning can be reduced, and the amount or concentration of the desired biological component can be measured with high accuracy and ease.

[0111] Implementation method 6.

[0112] The arithmetic unit 11 in embodiment 6 includes a learning device 91C, an inference device 95C, and a learned model storage device 94C.

[0113] Figure 13 This is a diagram showing the structure of the learning device 91C according to Embodiment 6. The learning device 91C includes a data acquisition unit 92C, a preprocessing unit 98C, and a model generation unit 93C.

[0114] The data acquisition unit 92C acquires data including the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material, and the amount or concentration of biological components.

[0115] The preprocessing unit 98C calculates an index β based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material.

[0116] The model generation unit 93C uses learning data, including index β and the amount or concentration BA of biological components, to generate a learned model for inferring the amount or concentration BA of biological components based on index β.

[0117] The learned model storage device 94C stores the learned model output from the model generation unit 93C.

[0118] Figure 14 This is a diagram showing the structure of the inference device 95C according to Embodiment 6. The inference device 95C includes a data acquisition unit 96C, a preprocessing unit 99C, and an inference unit 97C.

[0119] The data acquisition unit 96C acquires the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material.

[0120] The preprocessing unit 99C calculates an index β based on the position CP(A) of the emitted probe light 7b(A) detected by the light position detector 4 when sample 5 is a reference material, the position CP(C) of the emitted probe light 7b(C) detected by the light position detector 4 when sample 5 is a reference material, and the position CP(B) of the emitted probe light 7b(B) detected by the light position detector 4 when sample 5 is a biological material. The index β can be set, for example, as CP(B) - CP(A) - CP(C).

[0121] The inference unit 97C uses a learned model stored in the learned model storage device 94C for inferring the amount or concentration BA of the biological component based on the index β, and infers the amount or concentration BA of the biological component based on the index β calculated by the preprocessing unit 99C.

[0122] According to this embodiment, the amount of data and time related to learning can be reduced, and the amount or concentration of the desired biological component can be measured with high accuracy and ease.

[0123] In the above embodiments 1 to 6, the arithmetic unit 11 may also be configured to perform the corresponding actions using hardware or software of digital circuits.

[0124] Figure 15 This diagram illustrates the structure when the functions of the arithmetic logic unit 11 are implemented using software. The arithmetic logic unit 11 includes a processor 1001 connected to a bus 1002 and a memory 1000. The processor 1001 executes a program stored in the memory 1000.

[0125] The embodiments disclosed herein should be considered illustrative rather than restrictive at all points. The scope of this disclosure is not limited to the foregoing description but is shown by the claims, and is intended to include all modifications within the meaning and scope equivalent to the claims.

[0126] (Symbol Explanation)

[0127] 1: Excitation light source; 2: Probe light source; 3: Optical medium; 4: Optical position detector; 5: Sample; 6: Excitation light; 7, 7a, 7b: Probe light; 8: Refractive index gradient region; 11: Arithmetic unit; 20: Optical chopper; 21: Lock-in amplifier; 91, 91A, 91B, 91C: Learning device; 92, 92A, 92B, 92C, 96, 96A, 96B, 96C: Data acquisition unit; 93, 93A, 93B, 93C: Model generation unit; 94, 94A, 94B, 94C: Learned model storage device; 95, 95A, 95B, 95C: Inference device; 97A, 97B, 97C: Inference unit; 98B, 98C, 99B, 99C: Preprocessing unit; 1000: Memory; 1001: Processor; 1002: Bus.

Claims

1. A biological component measuring apparatus comprising: an optical medium including a sample placement surface; an excitation light source that radiates excitation light that advances in the optical medium and has an excitation wavelength of a sample placed on the sample placement surface; a probe light source that radiates probe light that advances in the optical medium; a light position detector that detects a position of emitted probe light emitted from the optical medium; and an arithmetic unit that calculates an amount or a concentration of a biological component in a biological substance based on the position of the emitted probe light detected by the light position detector when the sample is a reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance, the reference substance absorbing the excitation light and having no specific absorption peak within the excitation wavelength of the excitation light.

2. The biological component measuring apparatus according to claim 1, wherein the arithmetic unit includes a learning apparatus, the learning apparatus including: a data acquisition unit that acquires learning data including the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the biological substance, and the amount or the concentration of the biological component; and a model generation unit that generates a learned model for inferring the amount or the concentration of the biological component based on the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance, using the learning data.

3. The biological component measuring apparatus according to claim 1, wherein the arithmetic unit includes a learning apparatus, the learning apparatus including: a data acquisition unit that acquires data including the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the biological substance, and the amount or the concentration of the biological component; a preprocessing unit that calculates one index based on the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance; and a model generation unit that generates a learned model for inferring the amount or the concentration of the biological component based on the index, using learning data including the index and the amount or the concentration of the biological component.

4. The biological component measuring apparatus according to claim 1, wherein the arithmetic unit includes an inference apparatus, the inference apparatus including: a data acquisition unit that acquires the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance; and an inference unit that infers the amount or the concentration of the biological component based on the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The inference unit infers the amount or concentration of the biological component using a learned model for inferring the amount or concentration of the biological component from the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance, based on the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance acquired by the data acquisition unit.

5. The biological component measuring apparatus according to claim 1, wherein the operation device includes an inference device, the inference device includes: a data acquisition unit that acquires the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance; a preprocessing unit that calculates one index from the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance; and an inference unit that infers the amount or concentration of the biological component from the index using a learned model for inferring the amount or concentration of the biological component from the index.

6. The biological component measuring apparatus according to claim 1, wherein the operation device further calculates the amount or concentration of the biological component from the position of the emitted probe light detected by the light position detector when the sample is a reference substance that absorbs the excitation light and has one or more absorption peaks of the biological component within the excitation wavelength of the excitation light.

7. The biological component measuring apparatus according to claim 6, wherein the operation device includes a learning device, the learning device includes: a data acquisition unit that acquires learning data including the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the biological substance, and the amount or concentration of the biological component; and a model generation unit that generates a learned model for inferring the amount or concentration of the biological component from the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, and the position of the emitted probe light detected by the light position detector when the sample is the biological substance using the learning data.

8. The biological component measuring apparatus according to claim 6, wherein the operation means is provided with a learning device, the learning device includes: a data acquisition section that acquires data including the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, and the amount or concentration of the biological component; a preprocessing section that calculates one index from the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, and the position of the emitted probe light detected by the light position detector when the sample is the reference substance; and a model generation section that generates a learned model for inferring the amount or concentration of the biological component from the index using the learning data including the index and the amount or concentration of the biological component.

9. The biological component measuring apparatus according to claim 6, wherein the operation means is provided with an inference device, the inference device includes: a data acquisition section that acquires the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, and the position of the emitted probe light detected by the light position detector when the sample is the reference substance; and an inference section that infers the amount or concentration of the biological component from the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, and the position of the emitted probe light detected by the light position detector when the sample is the reference substance using a learned model for inferring the amount or concentration of the biological component from the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, and the position of the emitted probe light detected by the light position detector when the sample is the reference substance.

10. The biological component measuring apparatus according to claim 6, wherein the operation means is provided with an inference device, the inference device includes: a data acquisition unit that acquires a position of the emitted probe light detected by the light position detector when the sample is the reference substance, a position of the emitted probe light detected by the light position detector when the sample is the reference substance, and a position of the emitted probe light detected by the light position detector when the sample is the biological substance; a preprocessing unit that calculates one index from the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, and the position of the emitted probe light detected by the light position detector when the sample is the biological substance; and an inference unit that infers the amount or concentration of the biological component from the index calculated by the preprocessing unit using a learned model for inferring the amount or concentration of the biological component from the index.

11. The biological component measuring apparatus according to any one of claims 1 to 10, wherein the optical path of the probe light in the optical medium overlaps with the portion of the sample placement surface irradiated with the excitation light when the sample placement surface is viewed from above.

12. A biological component measuring method comprising: a step of radiating, by an excitation light source, excitation light that advances in an optical medium and has an excitation wavelength of a sample placed on a sample placement surface of the optical medium toward the sample; a step of radiating, by a probe light source, probe light that advances in the optical medium; a step of detecting, by a light position detector, a position of emitted probe light of the probe light incident to the optical medium when the sample is a reference substance; a step of detecting, by the light position detector, a position of emitted probe light of the probe light incident to the optical medium when the sample is a biological substance; and a step of calculating, by an arithmetic unit, an amount or concentration of a biological component in the biological substance from the position of the emitted probe light detected by the light position detector when the sample is the reference substance and the position of the emitted probe light detected by the light position detector when the sample is the biological substance, the reference substance absorbs the excitation light and has no specific absorption peak within the excitation wavelength of the excitation light.

13. The biological component measuring method according to claim 12, wherein the method further comprises a step of detecting, by the light position detector, a position of emitted probe light of the probe light incident to the optical medium when the sample is a reference substance, the step of calculating the amount or concentration of the biological component includes: the arithmetic unit calculates the amount or concentration of the biological component from the position of the emitted probe light detected by the light position detector when the sample is the reference substance, the position of the emitted probe light detected by the light position detector when the sample is the reference substance, and the position of the emitted probe light detected by the light position detector when the sample is the biological substance, The reference substance absorbs the excitation light and has an absorption peak of one or more biological components within an excitation wavelength of the excitation light.

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