Non-invasive substance analysis device and non-invasive substance analysis method

Abstract

The non-invasive substance analysis device (1) includes an optical medium (10), an excitation light source (20) that emits a first excitation light (21a), a light position detector (45), and a light path switcher (30). The optical medium (10) includes a first placement area (15) on which a sample (18) is placed, and a second placement area (16) on which a reference material (19) is placed. The light position detector (45) detects the position of a probe light (41) emitted from the optical medium (10). The light path switcher (30) switches the light path of the first excitation light (21a) between a first light path (24) and a second light path (25). The first placement area (15) is irradiated with the first excitation light (21a) traveling through the first light path (24). The second placement area (16) is irradiated with the first excitation light (21a) traveling along the second optical path (25).

Description

[Technical field]

[0001] The present disclosure relates to a non-invasive substance analysis device and a non-invasive substance analysis method. [Background technology]

[0002] JP2017-519214A (Patent Document 1) discloses a non-invasive analysis system including an optical medium, an excitation light source, a probe light source, and a photodiode. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2017-519214 Summary of the Invention [Problem to be solved by the invention]

[0004] However, in the noninvasive analysis system disclosed in Patent Document 1, when the noninvasive analysis system is used to continuously analyze a substance to be measured for a long period of time, the analysis conditions change, such as drift in the intensity of the excitation light and temperature drift in the surrounding environment, and the analysis accuracy of the noninvasive analysis system may decrease. The present disclosure has been made in view of the above problems, and its purpose is to provide a noninvasive substance analysis device and a noninvasive substance analysis method that have improved analysis accuracy over a long period of time. [Means for solving the problem]

[0005] The non-invasive substance analysis device of the present disclosure includes an optical medium, an excitation light source, a light position detector, and a light path switcher. The optical medium includes a first mounting area on which a sample is placed and a second mounting area on which a reference substance is placed. The excitation light source emits a first excitation light. The probe light source emits a probe light traveling through the optical medium. The light position detector detects the position of the probe light emitted from the optical medium. The light path switcher switches the light path of the first excitation light between the first light path and the second light path. The first mounting area is irradiated with the first excitation light traveling through the first light path. The second mounting area is irradiated with the first excitation light traveling through the second light path. The light position detector detects a first position of the probe light when the sample and reference substance are not irradiated with the first excitation light, a second position of the probe light when the first excitation light travels along the first optical path, and a third position of the probe light when the first excitation light travels along the second optical path.

[0006] The non-invasive substance analysis method of the present disclosure comprises placing a sample and a reference substance on a first placement region and a second placement region of an optical medium, respectively, and detecting a first position of a probe light emitted from the optical medium without irradiating the sample and the reference substance with a first excitation light. The non-invasive substance analysis method of the present embodiment comprises irradiating the sample with the first excitation light and detecting a second position of the probe light emitted from the optical medium, and irradiating the reference substance with the first excitation light by switching the optical path of the first excitation light and detecting a third position of the probe light emitted from the optical medium. The non-invasive substance analysis method of the present embodiment comprises analyzing a measurement target substance of the sample based on the first position, the second position, and the third position. Effect of the Invention

[0007] The non-invasive substance analysis device and non-invasive substance analysis method disclosed herein have improved analytical accuracy over a long period of time. [Brief description of the drawings]

[0008] [Figure 1] 1 is a schematic diagram of a noninvasive substance analysis device according to a first embodiment. [Diagram 2]1 is a schematic partially enlarged plan view of a noninvasive substance analyzing device according to a first embodiment. [Diagram 3] 1 is a schematic partial enlarged view of a noninvasive substance analysis device according to a first embodiment. [Figure 4] FIG. 2 is a circuit diagram of a lock-in amplifier. [Diagram 5] FIG. 2 is a block diagram illustrating a functional configuration of an analyzer. [Figure 6] FIG. 2 is a flowchart showing a noninvasive substance analysis method according to the first to third embodiments. [Figure 7] FIG. 2 is a flowchart showing steps for analyzing a substance to be measured in the noninvasive substance analysis methods according to the first to third embodiments. [Figure 8] FIG. 13 is a flowchart showing an example of steps for calculating the absorbance of a measurement target substance from a displacement distance. [Figure 9] FIG. 2 is a schematic diagram of a noninvasive substance analyzing device according to a first modified example of the first embodiment. [Figure 10] FIG. 13 is a schematic diagram of a noninvasive substance analyzing device according to a second modified example of the first embodiment. [Figure 11] FIG. 11 is a schematic diagram of a noninvasive substance analysis device according to a second embodiment. [Figure 12] FIG. 11 is a schematic diagram of a noninvasive substance analysis device according to a third embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Hereinafter, an embodiment will be described, in which the same reference numerals are used to refer to the same components, and the description thereof will not be repeated.

[0010] Embodiment 1 A noninvasive substance analyzing device 1 according to a first embodiment will be described with reference to FIGS.

[0011] The noninvasive substance analysis apparatus 1 mainly includes an optical medium 10, an excitation light source 20, an optical path switcher 30, a probe light source 40, an optical position detector 45, and an analyzer 50. The noninvasive substance analysis apparatus 1 may further include an optical intensity modulator 22, a controller 22c, and a lock-in amplifier 46. The noninvasive substance analysis apparatus 1 may further include a reflecting member 23.

[0012] 1 and 2, the optical medium 10 includes a first main surface 11, a second main surface 12 opposite to the first main surface 11, a first end surface 13, and a second end surface 14 opposite to the first end surface 13. The first end surface 13 and the second end surface 14 are connected to the first main surface 11 and the second main surface 12, respectively. The first main surface 11 is, for example, an incident surface of the excitation light 21. The second main surface 12 includes a first mounting area 15 on which the sample 18 is placed, and a second mounting area 16 on which the reference substance 19 is placed. The first end surface 13 is, for example, an incident surface of the probe light 41. The second end surface 14 is, for example, an exit surface of the probe light 41.

[0013] The optical medium 10 is made of a material whose refractive index is temperature dependent. The optical medium 10 is transparent to the excitation light 21 and the probe light 41. In this specification, the optical medium 10 being transparent to the excitation light 21 and the probe light 41 means that the optical transmittance of the optical medium 10 to the excitation light 21 and the probe light 41 is 25% or more. The optical transmittance of the optical medium 10 to the excitation light 21 and the probe light 41 may be 50% or more. The optical medium 10 is made of, for example, zinc sulfide (ZnS), zinc selenide (ZnSe), germanium (Ge), silicon (Si), chalcogenide glass, or the like.

[0014] 1 and 2, the sample 18 is a part of the subject's body, such as the subject's skin, finger, or wrist. The sample 18 includes a substance to be measured. The substance to be measured is, for example, a biological component. The biological component is, for example, sugar, protein, amino acid, sugar, fatty acid, hormone, or neurotransmitter in blood. The substance to be measured is on the surface of the sample 18 or in the sample 18. The sample 18 may be a solution including the substance to be measured. The sample 18 may further include a non-measurement substance. For example, when the sample 18 is an aqueous solution of the substance to be measured, the non-measurement substance is water.

[0015] The reference material 19 has an absorbance that is almost independent of changes in the surrounding environment (such as the surrounding temperature). The absorbance of the reference material 19 (more specifically, the absorbance of the reference material 19 at a first wavelength and a second wavelength described later) is known. The reference material 19 is, for example, a resin material or glass.

[0016] Referring to FIG. 1, the excitation light source 20 emits excitation light 21. The wavelength of the excitation light 21 may be longer than the wavelength of the probe light 41. The excitation light 21 is, for example, infrared light. The wavelength of the excitation light 21 is, for example, 6.0 μm or more. The wavelength of the excitation light 21 may be 8.0 μm or more. The wavelength of the excitation light 21 is, for example, 13.0 μm or less. The wavelength of the excitation light 21 may be 11.0 μm or less. For example, when the blood glucose level of a patient is measured using the non-invasive substance analyzer 1, the wavelength range of the excitation light 21 is a wavelength range including the wavelength of the fingerprint spectrum of sugar (for example, a wavelength range of 8.5 μm or more and 10 μm or less). The excitation light source 20 is, for example, a quantum cascade laser that can emit wideband infrared light.

[0017] The excitation light source 20 may be a tunable light source such as a tunable laser. The excitation light 21 may be light having a plurality of wavelengths. The excitation light source 20 may emit a first excitation light 21a having a first wavelength and a second excitation light 21b having a second wavelength different from the first wavelength. The first excitation light 21a is a measurement light, and the first wavelength is a measurement wavelength. The first wavelength is, for example, a peak wavelength of an absorption spectrum of a substance to be measured in the sample 18. The second excitation light 21b is a reference light, and the second wavelength is a reference wavelength. The second wavelength is, for example, a wavelength that is hardly absorbed by the substance to be measured.

[0018] The excitation light 21 is incident on the light intensity modulator 22. The controller 22c controls the light intensity modulator 22. For example, the controller 22c transmits a drive signal having a modulation frequency f to the light intensity modulator 22, and the light intensity modulator 22 modulates the light intensity of the excitation light 21 at the modulation frequency f. The controller 22c is, for example, a microcomputer or an electronic circuit. The light intensity modulator 22 is, for example, an optical chopper or an optical shutter. The optical chopper includes a blade (not shown) and a rotating mechanism (not shown) that rotates the blade. The optical shutter is, for example, an electro-optical modulator such as a liquid crystal optical shutter.

[0019] For example, if the substance to be measured is sugar in blood, the excitation light is absorbed by the sugar in the interstitial fluid near the surface of the sample 18. The components in the interstitial fluid change in conjunction with the components in the blood, so there is a correlation between the proportion of sugar in the interstitial fluid and the proportion of sugar in the blood (i.e., blood glucose level). The thermal diffusion length L of the sample 18 is (α / π·f) 1 / 2 where α is the thermal diffusion coefficient of the sample 18. f is the modulation frequency of the excitation light 21. Therefore, in order to measure the interstitial fluid at a depth of several tens of μm from the surface of the sample 18, the modulation frequency f is set to 5 Hz or more and 100 Hz or less.

[0020] The modulated excitation light 21 is reflected by the reflecting member 23 and enters the optical path switcher 30. The reflecting member 23 is, for example, a prism or a mirror.

[0021] Referring to FIG. 1, the light path switcher 30 switches the light path of the excitation light 21 between the first light path 24 and the second light path 25. The first mounting area 15 is irradiated with the excitation light 21 traveling through the first light path 24. The second mounting area 16 is irradiated with the excitation light 21 traveling through the second light path 25. The light path switcher 30 includes, for example, a movable reflecting member 31 and a moving mechanism 32 that moves the movable reflecting member 31. The movable reflecting member 31 is, for example, a prism or a mirror. The moving mechanism 32 moves the movable reflecting member 31 between a first position and a second position. When the movable reflecting member 31 is in the first position, the excitation light 21 travels through the first light path 24 toward the sample 18. When the movable reflecting member 31 is in the second position, the excitation light 21 travels through the first light path 24 toward the reference material 19. The moving mechanism 32 is, for example, a linear actuator including a ball screw (not shown) and a motor (not shown).

[0022] 1 and 2, the excitation light 21 emitted from the light path switcher 30 enters the optical medium 10 from the first main surface 11. The excitation light 21 travels through the optical medium 10. The first irradiation area 24a is irradiated with the excitation light 21 traveling through the first optical path 24. The first irradiation area 24a is an area of ​​the second main surface 12 irradiated with the excitation light 21 traveling through the first optical path 24. The first irradiation area 24a is inside the first placement area 15. The sample 18 is irradiated with the excitation light 21 traveling through the first optical path 24. The second irradiation area 25a is irradiated with the excitation light 21 traveling through the second optical path 25. The second irradiation area 25a is an area of ​​the second main surface 12 irradiated with the excitation light 21 traveling through the second optical path 25. The second irradiation area 25a is an area of ​​the second main surface 12 irradiated with the excitation light 21 traveling through the second optical path 25. The second irradiation area 25a is inside the second placement area 16. The reference material 19 is illuminated with excitation light 21 traveling along a second optical path 25 .

[0023] The excitation light 21 traveling along the first optical path 24 is absorbed by the analyte substance in the sample 18. Absorption of the excitation light 21 by the analyte substance generates absorbed heat in the sample 18. The absorbed heat in the sample 18 is conducted to the optical medium 10. A first temperature gradient region is created within the optical medium 10, and a first refractive index gradient region 27 is created within the optical medium 10.

[0024] The excitation light 21 traveling along the second optical path 25 is absorbed by the reference material 19. Absorption of the excitation light 21 by the reference material 19 generates absorbed heat in the reference material 19. The absorbed heat of the reference material 19 is conducted to the optical medium 10. A second temperature gradient region is created within the optical medium 10, and a second refractive index gradient region 28 is created within the optical medium 10.

[0025] 1, the probe light source 40 emits a probe light 41. The probe light 41 is, for example, visible light or near-infrared light. The probe light source 40 is, for example, a semiconductor laser.

[0026] The probe light 41 enters the optical medium 10 from the first end face 13 and travels through the optical medium 10. In this embodiment, the probe light 41 is not reflected at the first main surface 11 and the second main surface 12, passes through a portion of the optical medium 10 close to the second main surface 12, and is emitted from the second end face 14. As shown in FIG. 2, in a plan view of the first mounting area 15 or the second main surface 12, the optical path of the probe light 41 overlaps the first mounting area 15 and the second mounting area 16, and overlaps the first irradiation area 24a and the second irradiation area 25a. While the probe light 41 travels through the optical medium 10, the probe light 41 travels through the first refractive index gradient area 27 generated in the optical medium 10 by the heat absorbed by the sample 18, or travels through the second refractive index gradient area 28 generated in the optical medium 10 by the heat absorbed by the reference material 19. The probe light 41 is refracted in the first refractive index gradient region 27 or the second refractive index gradient region 28, and the traveling direction of the probe light 41 is changed.

[0027] The beam diameter of the excitation light 21 may be larger than the beam diameter of the probe light 41. Therefore, the entire probe light 41 passes through the first refractive index gradient region 27 and the second refractive index gradient region 28, and the change in the traveling direction of the probe light 41 due to the first refractive index gradient region 27 and the second refractive index gradient region 28 becomes large. This improves the analytical accuracy of the measurement target substance of the sample 18. For example, the beam diameter of the excitation light 21 is about 100 μm, and the beam diameter of the probe light 41 is about 50 μm.

[0028] 1 and 3, the optical position detector 45 is a semiconductor position detection element such as a segmented photodiode, etc. The optical position detector 45 detects the position of the probe light 41 emitted from the optical medium 10.

[0029] Specifically, the light position detector 45 detects positions 42a, 42b, 42c, 42d, and 42e of the probe light 41. The position 42a is the position of the probe light 41 detected by the light position detector 45 when the sample 18 and the reference substance 19 are not irradiated with the excitation light 21 (the first excitation light 21a and the second excitation light 21b). The position 42b is the position of the probe light 41 detected by the light position detector 45 when the sample 18 is irradiated with the first excitation light 21a. The position 42c is the position of the probe light 41 detected by the light position detector 45 when the sample 18 is irradiated with the second excitation light 21b. The position 42d is the position of the probe light 41 detected by the light position detector 45 when the reference substance 19 is irradiated with the first excitation light 21a. The position 42e is the position of the probe light 41 detected by the light position detector 45 when the reference substance 19 is irradiated with the second excitation light 21b.

[0030] When the sample 18 and the reference material 19 are not irradiated with the excitation light 21, the first refractive index gradient region 27 and the second refractive index gradient region 28 are not formed in the optical medium 10. In contrast, when the sample 18 is irradiated with the excitation light 21 (the first excitation light 21a and the second excitation light 21b), the first refractive index gradient region 27 is formed in the optical medium 10. When the reference material 19 is irradiated with the excitation light 21 (the first excitation light 21a and the second excitation light 21b), the second refractive index gradient region 28 is formed in the optical medium 10. The probe light 41 is refracted in the first refractive index gradient region 27 or the second refractive index gradient region 28. Therefore, when the sample 18 or the reference material 19 is irradiated with the excitation light 21, the incident position (positions 42b, 42c, 42d, 42e) of the probe light 41 on the light position detector 45 changes from position 42a.

[0031] The light position detector 45 outputs light position signals representing the incident position of the probe light 41 on the light position detector 45 to the analyzer 50 through the lock-in amplifier 46. The light position signals include a first light position signal representing position 42a, a second light position signal representing position 42b, a third light position signal representing position 42c, a fourth light position signal representing position 42d, and a fifth light position signal representing position 42e. When the light intensity modulator 22 modulates the light intensity of the excitation light 21 at the modulation frequency f, the light position signals have the modulation frequency f.

[0032] 1, the lock-in amplifier 46 is connected to the controller 22c of the optical intensity modulator 22 and the optical position detector 45. The lock-in amplifier 46 selectively amplifies a signal that is synchronized with the modulation frequency f of the excitation light 21, among the optical position signals output from the optical position detector 45. Therefore, noise contained in the optical position signal output from the optical position detector 45 is removed.

[0033] For example, as shown in FIG. 4, the lock-in amplifier 46 includes a multiplier 47 and a low-pass filter 48. The lock-in amplifier 46 receives the light position signal from the light position detector 45, and also receives from the controller 22c a drive signal output from the controller 22c to the light intensity modulator 22 and having a modulation frequency f. The multiplier 47 multiplies the light position signal by the drive signal of the controller 22c. The light position signal and the drive signal of the controller 22c are equal in frequency. Therefore, when the light position signal is multiplied by the drive signal of the controller 22c, a frequency component of 2f and a DC component are obtained. The low-pass filter 48 removes the frequency component of 2f and passes only the DC component. In this way, the noise contained in the light position signal is removed.

[0034] With reference to FIG. 1, the analyzer 50 analyzes the measurement target substance of the sample 18 based on the positions 42a-42e. The analyzer 50 is, for example, a microcomputer including a processor, a storage device such as a RAM (Random Access Memory), and a ROM (Read Only Memory). For example, a CPU (Central Processing Unit) may be adopted as the processor. The RAM functions as a working memory that temporarily stores data processed by the processor. For example, the storage device stores a program executed by the processor. In this embodiment, the analyzer 50 analyzes the measurement target substance of the sample 18 by the processor executing the program stored in the storage device. Various processes in the analyzer 50 are not limited to being executed by software, and may be realized by dedicated hardware (electronic circuitry).

[0035] With reference to FIG. 5, the analyzer 50 includes, for example, a displacement distance calculation unit 51 and an analysis unit 52.

[0036] The displacement distance calculation unit 51 calculates a displacement distance ΔD1 (see FIG. 3) of the probe light 41, which is the difference between the positions 42b and 42a, from the first light position signal representing the position 42a and the second light position signal representing the position 42b. The displacement distance calculation unit 51 calculates a displacement distance ΔD2 (see FIG. 3) of the probe light 41, which is the difference between the positions 42c and 42a, from the first light position signal representing the position 42a and the third light position signal representing the position 42c. The displacement distance calculation unit 51 calculates a displacement distance ΔD3 (see FIG. 3) of the probe light 41, which is the difference between the positions 42d and 42a, from the first light position signal representing the position 42a and the fourth light position signal representing the position 42d. The displacement distance calculation unit 51 calculates a displacement distance ΔD4 (see FIG. 3) of the probe light 41, which is the difference between the position 42e and the position 42a, from the first light position signal representing the position 42a and the fifth light position signal representing the position 42e.

[0037] The analysis unit 52 analyzes the target substance of the sample 18 based on the displacement distances ΔD1, ΔD2, ΔD3, and ΔD4. For example, the analysis unit 52 calculates the absorbance of the target substance at the measurement wavelength based on the displacement distances ΔD1, ΔD2, ΔD3, and ΔD4. The absorbance of the target substance is proportional to the amount or concentration of the target substance. The analysis unit 52 may calculate the amount or concentration of the target substance from the absorbance of the target substance.

[0038] The non-invasive substance analysis method of this embodiment will be described with reference to FIGS. 6, the sample 18 and the reference substance 19 are placed on the optical medium 10 (step S1). Specifically, the sample 18 is placed on the first placement area 15, and the reference substance 19 is placed on the second placement area 16.

[0039] 6, the position 42a of the probe light 41 is detected without irradiating the sample 18 and the reference substance 19 with the excitation light 21 (the first excitation light 21a and the second excitation light 21b) (step S2). Specifically, the excitation light source 20 does not emit the excitation light 21. Therefore, the first refractive index gradient region 27 and the second refractive index gradient region 28 are not formed in the optical medium 10. The probe light source 40 emits the probe light 41. The probe light 41 enters from the first end face 13, passes through the optical medium 10, and exits from the second end face 14. The light position detector 45 detects the position 42a of the probe light 41.

[0040] Referring to FIG. 6, the sample 18 is irradiated with the first excitation light 21a, and the position 42b of the probe light 41 is detected (step S3).

[0041] Specifically, the excitation light source 20 emits a first excitation light 21a. The first excitation light 21a has a first wavelength. The first excitation light 21a is a measurement light, and the first wavelength is a measurement wavelength. The first wavelength is, for example, a peak wavelength of the absorption spectrum of the substance to be measured. The light intensity modulator 22 intensity-modulates the first excitation light 21a at a modulation frequency f. The modulated first excitation light 21a is reflected by the reflecting member 23 and enters the optical path switcher 30. The moving mechanism 32 moves the movable reflecting member 31 to a first position to switch the optical path of the first excitation light 21a to the first optical path 24. The first excitation light 21a travels through the first optical path 24. The first excitation light 21a enters the optical medium 10 from the first main surface 11. The first excitation light 21a passes through the optical medium 10 and enters the sample 18. The sample 18 is illuminated with the first excitation light 21a. The reference material 19 is not illuminated with the first excitation light 21a.

[0042] The first excitation light 21a traveling through the first optical path 24 is absorbed by the analyte and non-analyte substances in the sample 18. Absorption of the first excitation light 21a by the analyte and non-analyte substances generates absorbed heat in the sample 18. The absorbed heat in the sample 18 is conducted to the optical medium 10. A first temperature gradient region is generated inside the optical medium 10, and a first refractive index gradient region 27 is generated inside the optical medium 10. The probe light 41 enters from the first end face 13. The probe light 41 is refracted in the first refractive index gradient region 27 and exits from the second end face 14. The optical position detector 45 detects a position 42b of the probe light 41. The position 42b is different from the position 42a.

[0043] 6, the sample 18 is irradiated with the second excitation light 21b to detect the position 42c of the probe light 41 (step S4). Step S4 is similar to step S3, but in step S4, the excitation light source 20 emits the second excitation light 21b, and the sample 18 is irradiated with the second excitation light 21b. The second excitation light 21b is a reference light, and the second wavelength is a reference wavelength. The second wavelength is, for example, a wavelength that is not absorbed by the substance to be measured.

[0044] Specifically, the excitation light source 20 emits the second excitation light 21b. The second excitation light 21b modulated by the optical intensity modulator 22 travels through the first optical path 24. The sample 18 is irradiated with the second excitation light 21b. The second excitation light 21b is absorbed by the non-measurement target substance of the sample 18. The measurement target substance of the sample 18 does not absorb the second excitation light 21b. Absorption of the second excitation light 21b by the non-measurement target substance generates absorption heat in the sample 18. The absorption heat of the sample 18 is conducted to the optical medium 10. A first temperature gradient region is generated inside the optical medium 10, and a first refractive index gradient region 27 is generated inside the optical medium 10. The probe light 41 is refracted in the first refractive index gradient region 27 and is emitted from the second end face 14. The optical position detector 45 detects the position 42c of the probe light 41. The first refractive index gradient region 27 in step S4 differs from the first refractive index gradient region 27 in step S3 in the degree and range of refractive index change, so that position 42c differs from positions 42a and 42b.

[0045] 6, the reference material 19 is irradiated with the first excitation light 21a, and the position 42d of the probe light 41 is detected (step S5). Step S5 is similar to step S3, but in step S5, the optical path of the excitation light 21 is switched to the second optical path 25, and the reference material 19 is irradiated with the first excitation light 21a. The sample 18 is not irradiated with the first excitation light 21a.

[0046] Specifically, the excitation light source 20 emits a first excitation light 21a. The first excitation light 21a modulated by the optical intensity modulator 22 is incident on the optical path switcher 30. The moving mechanism 32 moves the movable reflecting member 31 to a second position to switch the optical path of the excitation light 21 to the second optical path 25. The first excitation light 21a travels through the second optical path 25. The first excitation light 21a is incident on the optical medium 10 from the first main surface 11. The second excitation light 21b passes through the optical medium 10 and is incident on the reference material 19.

[0047] The first excitation light 21a traveling through the second optical path 25 is absorbed by the reference material 19. Absorption of the first excitation light 21a by the reference material 19 generates absorbed heat in the reference material 19. The absorbed heat of the reference material 19 is conducted to the optical medium 10. A second temperature gradient region is generated inside the optical medium 10, and a second refractive index gradient region 28 is generated inside the optical medium 10. The probe light 41 enters from the first end face 13. The probe light 41 is refracted in the second refractive index gradient region 28 and exits from the second end face 14. The optical position detector 45 detects a position 42d of the probe light 41. The position 42d is different from the position 42a.

[0048] 6, the reference material 19 is irradiated with the second excitation light 21b to detect the position 42e of the probe light 41 (step S6). Step S6 is similar to step S5, but in step S6, the excitation light source 20 emits the second excitation light 21b and the reference material 19 is irradiated with the second excitation light 21b. The sample 18 is not irradiated with the second excitation light 21b.

[0049] Specifically, the excitation light source 20 emits the second excitation light 21b. The second excitation light 21b modulated by the optical intensity modulator 22 travels along the second optical path 25. The reference material 19 is irradiated with the second excitation light 21b. The second excitation light 21b is absorbed by the reference material 19. Absorption of the second excitation light 21b by the reference material 19 generates absorption heat in the reference material 19. The absorption heat of the reference material 19 is conducted to the optical medium 10. A second temperature gradient region is generated inside the optical medium 10, and a second refractive index gradient region 28 is generated inside the optical medium 10. The probe light 41 is refracted in the second refractive index gradient region 28 and is emitted from the second end surface 14. The optical position detector 45 detects a position 42e of the probe light 41. The position 42e is different from the position 42a.

[0050] The light position detector 45 outputs a light position signal representing the incident position (positions 42a-42e) of the probe light 41 on the light position detector 45 to the analyzer 50 through the lock-in amplifier 46. The light position signal includes a first light position signal representing the position 42a, a second light position signal representing the position 42b, a third light position signal representing the position 42c, a fourth light position signal representing the position 42d, and a fifth light position signal representing the position 42e. When the light intensity modulator 22 modulates the light intensity of the excitation light 21 at the modulation frequency f, the light position signal has a modulation frequency f. The lock-in amplifier 46 removes noise contained in the light position signal and amplifies the signal.

[0051] For example, the lock-in amplifier 46 is connected to the controller 22c of the optical intensity modulator 22 and the optical position detector 45. The lock-in amplifier 46 receives the optical position signal output from the optical position detector 45, and also receives from the controller 22c the drive signal output from the controller 22c to the optical intensity modulator 22 and having a modulation frequency f. As shown in FIG. 4, the lock-in amplifier 46 includes a multiplier 47 and a low-pass filter 48. The multiplier 47 multiplies the optical position signal by the drive signal of the controller 22c. This multiplication results in a 2f frequency component and a DC component. The low-pass filter 48 removes the 2f frequency component and passes only the DC component. In this way, noise contained in the optical position signal is removed.

[0052] Referring to FIG. 6, the measurement target substance in the sample 18 is analyzed based on the positions 42a-42e (step S7).

[0053] Specifically, analyzer 50 receives the optical position signals from which noise has been removed at lock-in amplifier 46. As previously described, the optical position signals include a first optical position signal representative of position 42a, a second optical position signal representative of position 42b, a third optical position signal representative of position 42c, a fourth optical position signal representative of position 42d, and a fifth optical position signal representative of position 42e.

[0054] 7, the displacement distance calculation unit 51 (see FIG. 5) calculates a displacement distance ΔD1 (see FIG. 3) of the probe light 41, which is the difference between the positions 42b and 42a, from the first light position signal representing the position 42a and the second light position signal representing the position 42b (step S11). ΔD1 is proportional to the sum of the absorbance of the measurement target substance of the sample 18 and the absorbance of the non-measurement target substance of the sample 18 at the first wavelength of the first excitation light 21a.

[0055] The displacement distance calculation unit 51 calculates a displacement distance ΔD2 of the probe light 41, which is a difference between the positions 42c and 42a, from the first light position signal representing the position 42a and the third light position signal representing the position 42c (step S12). ΔD2 is proportional to the absorbance of the non-measurement target substance of the sample 18 at the second wavelength of the second excitation light 21b.

[0056] The displacement distance calculation unit 51 calculates a displacement distance ΔD3 (see FIG. 3) of the probe light 41, which is the difference between the positions 42d and 42a, from the first light position signal representing the position 42a and the fourth light position signal representing the position 42d (step S13). ΔD3 is proportional to the absorbance of the reference material 19 at the first wavelength of the first excitation light 21a.

[0057] The displacement distance calculation unit 51 calculates a displacement distance ΔD4 of the probe light 41, which is a difference between the positions 42e and 42a, from the first light position signal representing the position 42a and the fifth light position signal representing the position 42e (step S14). ΔD4 is proportional to the absorbance of the reference material 19 at the second wavelength of the second excitation light 21b.

[0058] The analysis unit 52 (see FIG. 5) analyzes the measurement target substance of the sample 18 based on the displacement distances ΔD1, ΔD2, ΔD3, and ΔD4 (step S15). For example, the analysis unit 52 (see FIG. 5) calculates the absorbance of the measurement target substance at the measurement wavelength based on the displacement distances ΔD1, ΔD2, ΔD3, and ΔD4. With reference to FIG. 8, an example of step S15 will be described below in which the absorbance of the non-measurement target substance of the sample 18 at the second wavelength of the second excitation light 21b can be considered to be substantially equal to the absorbance of the non-measurement target substance of the sample 18 at the first wavelength of the first excitation light 21a.

[0059] The analysis unit 52 calculates the product of the absorbance of the reference substance 19 at the first wavelength (measurement wavelength) of the first excitation light 21a and ΔD1 / ΔD3 (step S16). The displacement distances ΔD1 and ΔD3 are both obtained by the first excitation light 21a having the first wavelength. As already described, ΔD1 is proportional to the sum of the absorbance of the measurement target substance of the sample 18 at the first wavelength and the absorbance of the non-measurement target substance of the sample 18 at the first wavelength. ΔD3 is proportional to the absorbance of the reference substance 19 at the first wavelength. The absorbance of the reference substance 19 at the first wavelength of the first excitation light 21a is known. Therefore, the sum of the absorbance of the measured substance at the first wavelength of the first excitation light 21a and the absorbance of the non-measured substance at the first wavelength of the first excitation light 21a is given by the product of the absorbance of the reference substance 19 at the first wavelength of the first excitation light 21a and ΔD1 / ΔD3.

[0060] The analysis unit 52 calculates the product of the absorbance of the reference substance 19 at the second wavelength (reference wavelength) of the second excitation light 21b and ΔD2 / ΔD4 (step S17). The displacement distances ΔD2 and ΔD4 are both obtained by the second excitation light 21b having the second wavelength. As already described, ΔD2 is proportional to the absorbance of the non-measurement target substance of the sample 18 at the second wavelength. ΔD4 is proportional to the absorbance of the reference substance 19 at the second wavelength. The absorbance of the reference substance 19 at the second wavelength of the second excitation light 21b is known. Therefore, the absorbance of the non-measurement target substance at the second wavelength of the second excitation light 21b is given by the product of the absorbance of the reference substance 19 at the second wavelength of the second excitation light 21b and ΔD2 / ΔD4.

[0061] When the absorbance of the non-measured substance at the first wavelength of the first excitation light 21a is equal to the absorbance of the non-measured substance at the second wavelength of the second excitation light 21b, the absorbance of the measured substance at the first wavelength (measurement wavelength) is obtained by subtracting the product of the absorbance of the reference substance 19 at the second wavelength of the second excitation light 21b calculated in step S17 and ΔD2 / ΔD4 from the product of the absorbance of the reference substance 19 at the first wavelength of the first excitation light 21a calculated in step S16 and ΔD1 / ΔD3. Therefore, the analysis unit 52 subtracts the product of the absorbance of the reference substance 19 at the second wavelength of the second excitation light 21b calculated in step S17 and ΔD2 / ΔD4 from the product of the absorbance of the reference substance 19 at the first wavelength of the first excitation light 21a calculated in step S16 and ΔD1 / ΔD3 (step S18). In this manner, analyzer 50 calculates the absorbance of the substance to be measured at the first wavelength.

[0062] The absorbance of the target substance is proportional to the amount or concentration of the target substance. Analysis unit 52 may calculate the amount or concentration of the target substance from the absorbance of the target substance. The analysis result of the target substance of sample 18 by noninvasive substance analyzer 1 may be the amount or concentration of the target substance.

[0063] The operation of this embodiment will now be described. Drift phenomena such as drift in ambient temperature, drift in the light intensity of excitation light 21, drift in the irradiation position of excitation light 21, and drift in the light intensity of probe light 41 cause changes in the incident position of probe light 41 on light position detector 45. Therefore, the drift phenomenon reduces the analysis accuracy of the measurement target substance by noninvasive substance analysis device 1. In this specification, drift means gradual changes in ambient temperature, light intensity of excitation light 21, irradiation position of excitation light 21, light intensity of probe light 41, etc. while noninvasive substance analysis device 1 is used for a long period of time.

[0064] In this embodiment, a sample 18 and a reference substance 19 are placed on an optical medium 10. Either the sample 18 or the reference substance 19 is irradiated with the excitation light 21 by switching the optical path of the excitation light 21. The time required to switch the optical path of the excitation light 21 is sufficiently shorter than the time scale on which a non-negligible change in the incident position of the probe light 41 due to the drift phenomenon occurs. Therefore, the influence of the drift phenomenon on the analysis results of the measurement target substance of the sample 18 can be eliminated. The analysis accuracy of the non-invasive substance analyzer 1 is improved over a long period of time.

[0065] Moreover, the sample 18 often includes a substance to be measured and a substance not to be measured. The excitation light 21 is absorbed by the substance to be measured and the substance not to be measured, and both the substance to be measured and the substance not to be measured generate heat. The first refractive index gradient region 27 is formed by the heat from the substance to be measured and the heat from the substance not to be measured. The non-measured substance reduces the analytical accuracy of the substance to be measured. In this embodiment, the sample 18 and the reference substance 19 are irradiated with the second excitation light 21b having a second wavelength that is hardly absorbed by the substance to be measured. Therefore, the influence of the non-measured substance on the analytical result of the substance to be measured of the sample 18 can be removed by using the positions 42c and 42e of the probe light 41 when the sample 18 and the reference substance 19 are irradiated with the second excitation light 21b. The analytical accuracy of the non-invasive substance analyzer 1 is improved over a long period of time.

[0066] (Modification) 9, in a first modified example of the present embodiment, the optical intensity modulator 22 may be omitted, and the controller 22c may control the excitation light source 20. Specifically, the controller 22c may transmit a drive signal having a modulation frequency f to the excitation light source 20, so that the excitation light source 20 emits excitation light 21 whose intensity is modulated at the modulation frequency f.

[0067] 10 , in a second modification of the present embodiment, the optical intensity modulator 22 and the movable reflecting member 31 are omitted, and the controller 22c controls the excitation light source 20, and the moving mechanism 32 may be connected to the excitation light source 20. The moving mechanism 32 may move the excitation light source 20 to switch the optical path of the excitation light 21 between the first optical path 24 and the second optical path 25.

[0068] Other modified examples of this embodiment will be described. The first excitation light 21a may have a plurality of first wavelengths, and the analyzer 50 may output an absorption spectrum of the measurement target substance of the sample 18. In addition, when the sample 18 does not contain a non-measurement target substance, or when the absorption of the first excitation light 21a by the non-measurement target substance is negligible compared to the absorption of the first excitation light 21a by the measurement target substance, the excitation light source 20 may not emit the second excitation light 21b, steps S4 and S6 may be omitted, the measurement target substance may be analyzed based on the positions 42a, 42b, and 42d in step S7, and the measurement target may be analyzed based on the displacement distance ΔD1 and the displacement distance ΔD3 in step S15.

[0069] Furthermore, the substance to be measured in the sample 18 may be analyzed based on a change in the phase of the probe light 41 instead of a change in the position of the probe light 41. The change in the phase of the probe light can be detected by the lock-in amplifier 46 as a difference between the phase of the light position signal output from the light position detector 45 and the phase of the drive signal of the light intensity modulator 22 output from the controller 22c.

[0070] The effects of the noninvasive substance analyzing device 1 of this embodiment will be described. The non-invasive substance analysis device 1 of this embodiment includes an optical medium 10, an excitation light source 20, a probe light source 40, a light position detector 45, and a light path switcher 30. The optical medium 10 includes a first mounting area 15 on which a sample 18 is placed, and a second mounting area 16 on which a reference material 19 is placed. The excitation light source 20 emits a first excitation light 21a. The probe light source 40 emits a probe light 41 traveling through the optical medium 10. The light position detector 45 detects the position of the probe light 41 emitted from the optical medium 10. The light path switcher 30 switches the light path of the first excitation light 21a between the first light path 24 and the second light path 25. The first mounting area 15 is irradiated with the first excitation light 21a traveling through the first light path 24. The second mounting area 16 is irradiated with the first excitation light 21a traveling through the second optical path 25. The light position detector 45 detects a first position (position 42a) of the probe light 41 when the sample 18 and the reference substance 19 are not irradiated with the first excitation light 21a, a second position (position 42b) of the probe light 41 when the first excitation light 21a travels through the first optical path 24, and a third position (position 42d) of the probe light 41 when the first excitation light 21a travels through the second optical path 25.

[0071] Therefore, it is possible to eliminate the effects of drift phenomena such as the drift of the ambient temperature, the drift of the light intensity of the excitation light 21, the drift of the irradiation position of the excitation light 21, and the drift of the light intensity of the probe light 41 from the analysis results of the measurement target substance of the sample 18. The analytical accuracy of the noninvasive substance analyzer 1 is improved over a long period of time.

[0072] Furthermore, the second position (position 42b) and the third position (position 42d) of the probe light 41 can be detected simply by switching the optical path of the first excitation light 21a. Therefore, the influence of the drift phenomenon can be removed more quickly and more accurately from the analysis results of the measurement target substance of the sample 18. The analysis accuracy and analysis speed of the noninvasive substance analyzer 1 are improved.

[0073] The noninvasive substance analysis device 1 of the present embodiment further includes an analyzer 50. The analyzer 50 analyzes the measurement target substance of the sample 18 based on the first position (position 42a), the second position (position 42b), and the third position (position 42d).

[0074] Therefore, it is possible to remove the influence of the drift phenomenon from the analysis results of the measurement target substance of the sample 18. The analysis precision of the noninvasive substance analysis device 1 is improved over a long period of time.

[0075] In the noninvasive substance analyzing device 1 of this embodiment, the analyzer 50 includes a displacement distance calculation section 51 and an analysis section 52. The displacement distance calculation section 51 calculates a first displacement distance (displacement distance ΔD1) of the probe light 41 which is the difference between the second position (position 42b) and the first position (position 42a), and a second displacement distance (displacement distance ΔD3) of the probe light 41 which is the difference between the third position (position 42d) and the first position (position 42a). The analysis section 52 analyzes the measurement target substance based on the first displacement distance and the second displacement distance.

[0076] Therefore, it is possible to remove the influence of the drift phenomenon from the analysis results of the measurement target substance of the sample 18. The analysis precision of the noninvasive substance analysis device 1 is improved over a long period of time.

[0077] In the noninvasive substance analysis device 1 of this embodiment, the excitation light source 20 emits the second excitation light 21b having a wavelength different from the first excitation light 21a. The optical path switcher 30 switches the optical path of the second excitation light 21b between the first optical path 24 and the second optical path 25. The first placement area 15 is irradiated with the second excitation light 21b traveling through the first optical path 24. The second placement area 16 is irradiated with the second excitation light 21b traveling through the second optical path 25. The optical position detector 45 detects a first position (position 42a) of the probe light 41 when the sample 18 and the reference material 19 are not irradiated with the first excitation light 21a and the second excitation light 21b. The light position detector 45 further detects a fourth position (position 42c) of the probe light 41 when the second excitation light 21b travels through the first optical path 24, and a fifth position (position 42e) of the probe light 41 when the second excitation light 21b travels through the second optical path 25.

[0078] Therefore, even if sample 18 contains non-target substances in addition to the target substance, it is possible to eliminate the influence of the non-target substances on the analysis results of the target substances in sample 18. The analytical accuracy of noninvasive substance analysis device 1 is improved over a long period of time.

[0079] The noninvasive substance analysis device 1 of this embodiment further includes an analyzer 50. The analyzer 50 analyzes the measurement target substance of the sample 18 based on the first position (position 42a), the second position (position 42b), the third position (position 42d), the fourth position (position 42c), and the fifth position (position 42d).

[0080] Therefore, even if sample 18 contains non-target substances in addition to the target substance, it is possible to eliminate the influence of the non-target substances on the analysis results of the target substances in sample 18. The analytical accuracy of noninvasive substance analysis device 1 is improved over a long period of time.

[0081] In the non-invasive substance analysis device 1 of this embodiment, the analyzer 50 includes a displacement distance calculation section 51 and an analysis section 52. The displacement distance calculation section 51 calculates a first displacement distance (displacement distance ΔD1) of the probe light 41 which is a difference between the second position (position 42b) and the first position (position 42a), a second displacement distance (displacement distance ΔD3) of the probe light 41 which is a difference between the third position (position 42d) and the first position, a third displacement distance (displacement distance ΔD2) of the probe light 41 which is a difference between the fourth position (position 42c) and the first position, and a fourth displacement distance (displacement distance ΔD4) of the probe light 41 which is a difference between the fifth position (position 42e) and the first position. The analysis section 52 analyzes the measurement target substance based on the first displacement distance, the second displacement distance, the third displacement distance, and the fourth displacement distance.

[0082] Therefore, even if sample 18 contains non-target substances in addition to the target substance, it is possible to eliminate the influence of the non-target substances on the analysis results of the target substances in sample 18. The analytical accuracy of noninvasive substance analysis device 1 is improved over a long period of time.

[0083] In the noninvasive substance analyzing device 1 of this embodiment, the light path switcher 30 includes a movable reflecting member 31 and a moving mechanism 32 that moves the movable reflecting member 31.

[0084] Therefore, the optical path of the first excitation light 21a can be switched between the first optical path 24 and the second optical path 25. The analysis accuracy and analysis speed of the noninvasive substance analysis device 1 are improved.

[0085] In the noninvasive substance analysis device 1 of this embodiment, the optical path switcher 30 includes a moving mechanism 32 that moves the excitation light source 20 .

[0086] Therefore, the optical path of the first excitation light 21a can be switched between the first optical path 24 and the second optical path 25. The analysis accuracy and analysis speed of the noninvasive substance analysis device 1 are improved.

[0087] In the noninvasive substance analysis device 1 of this embodiment, the optical medium 10 includes a first main surface 11, a second main surface 12 opposite to the first main surface 11, a first end surface 13, and a second end surface 14 opposite to the first end surface 13. The first end surface 13 and the second end surface 14 are connected to the first main surface 11 and the second main surface 12, respectively. The first excitation light 21a enters the optical medium 10 from the first main surface 11. The second main surface 12 includes a first mounting region 15 and a second mounting region 16. The probe light 41 enters the optical medium 10 from the first end surface 13 and exits from the second end surface 14 without being reflected by the first main surface 11 and the second main surface 12.

[0088] Both the first mounting area 15 and the second mounting area 16 are part of the second main surface 12. This makes it easy to mount the sample 18 and the reference substance 19 on the optical medium 10.

[0089] The non-invasive substance analysis method of this embodiment includes placing a sample 18 and a reference substance 19 on the first mounting region 15 and the second mounting region 16 of the optical medium 10, respectively (step S1), and detecting a first position (position 42a) of the probe light 41 emitted from the optical medium 10 without irradiating the sample 18 and the reference substance 19 with the first excitation light 21a (step S2). The non-invasive substance analysis method of this embodiment includes irradiating the sample 18 with the first excitation light 21a and detecting a second position (position 42b) of the probe light 41 emitted from the optical medium 10 (step S3), and irradiating the reference substance 19 with the first excitation light 21a by switching the optical path of the first excitation light 21a and detecting a third position (position 42d) of the probe light 41 emitted from the optical medium 10 (step S5). The non-invasive substance analysis method of the present embodiment includes analyzing the measurement target substance of the sample 18 based on the first position, the second position, and the third position (step S7).

[0090] Therefore, it is possible to eliminate the influence of drift phenomena such as the drift of the ambient temperature, the drift of the light intensity of the excitation light 21, the drift of the irradiation position of the excitation light 21, and the drift of the light intensity of the probe light 41 from the analysis results of the measurement target substance of the sample 18. The analytical accuracy of the non-invasive substance analysis method is improved over a long period of time.

[0091] Moreover, the second position (position 42b) and the third position (position 42d) of the probe light 41 can be detected simply by switching the optical path of the first excitation light 21a. Therefore, the influence of the drift phenomenon can be more quickly and more accurately removed from the analysis results of the measurement target substance of the sample 18. The analysis accuracy and analysis speed of the non-invasive substance analysis method are improved.

[0092] In the noninvasive substance analysis method of this embodiment, analyzing the substance to be measured (step S7) includes calculating a first displacement distance (displacement distance ΔD1) of the probe light 41, which is the difference between the second position (position 42b) and the first position (position 42a), and a second displacement distance (displacement distance ΔD3) of the probe light 41, which is the difference between the third position (position 42d) and the first position (steps S11, S13), and analyzing the substance to be measured based on the first displacement distance and the second displacement distance (step S15).

[0093] Therefore, the influence of the drift phenomenon can be removed from the analysis results of the measurement target substance of the sample 18. The analytical accuracy of the non-invasive substance analysis method is improved over a long period of time.

[0094] The non-invasive substance analysis method of this embodiment further includes irradiating the sample 18 with the second excitation light 21b having a wavelength different from the first excitation light 21a to detect a fourth position (position 42c) of the probe light 41 emitted from the optical medium 10 (step S4), and irradiating the reference substance 19 with the second excitation light 21b by switching the optical path of the second excitation light 21b to detect a fifth position (position 42e) of the probe light 41 emitted from the optical medium 10 (step S6). The first position (position 42a) is detected without irradiating the first excitation light 21a and the second excitation light 21b. The measurement target substance is analyzed based on the first position, the second position (position 42b), the third position (position 42d), the fourth position, and the fifth position (step S7).

[0095] Therefore, even if sample 18 contains non-target substances in addition to the target substance, it is possible to eliminate the influence of the non-target substances on the analysis results of the target substances in sample 18. The analytical accuracy of the non-invasive substance analysis method is improved over a long period of time.

[0096] In the noninvasive substance analysis method of this embodiment, analyzing the substance to be measured includes calculating a first displacement distance (displacement distance ΔD1) of probe light 41 which is the difference between the second position (position 42b) and the first position (position 42a), a second displacement distance of probe light 41 which is the difference between the third position (position 42d) and the first position, a third displacement distance (displacement distance ΔD2) of probe light 41 which is the difference between the fourth position (position 42c) and the first position, and a fourth displacement distance (displacement distance ΔD4) of probe light 41 which is the difference between the fifth position (position 42e) and the first position (steps S11-S14), and analyzing the substance to be measured based on the first displacement distance, the second displacement distance, the third displacement distance, and the fourth displacement distance (step S15).

[0097] Therefore, even if sample 18 contains non-target substances in addition to the target substance, it is possible to eliminate the influence of the non-target substances on the analysis results of the target substances in sample 18. The analytical accuracy of the non-invasive substance analysis method is improved over a long period of time.

[0098] Embodiment 2 A noninvasive material analysis apparatus 1 of the second embodiment will be described with reference to Fig. 11. The noninvasive material analysis apparatus 1 of the present embodiment has a similar configuration to the noninvasive material analysis apparatus 1 of the first embodiment, but differs mainly in the following points.

[0099] In the noninvasive substance analysis device 1 of this embodiment, the optical path switcher 30 includes a beam splitter 33 , a reflecting member 34 , a first optical shutter 35 , a second optical shutter 36 , and a shutter controller 37 .

[0100] The beam splitter 33 splits the excitation light 21 (the first excitation light 21a and the second excitation light 21b) into a first beam that travels along the first optical path 24 and a second beam that travels along the second optical path 25. The reflecting member 34 reflects the second beam.

[0101] The first optical shutter 35 is disposed on the first optical path 24. The second optical shutter 36 is disposed on the second optical path 25. The first optical shutter 35 and the second optical shutter 36 are, for example, electro-optical modulators such as liquid crystal optical shutters. The shutter controller 37 is connected to the first optical shutter 35 and the second optical shutter 36 and controls the first optical shutter 35 and the second optical shutter 36. The shutter controller 37 switches the first optical shutter 35 between an open state in which the excitation light 21 traveling through the first optical path 24 passes and a closed state in which the excitation light 21 traveling through the first optical path 24 is blocked. The shutter controller 37 switches the second optical shutter 36 between an open state in which the excitation light 21 traveling through the second optical path 25 passes and a closed state in which the excitation light 21 traveling through the second optical path 25 is blocked. The shutter controller 37 is, for example, a microcomputer or an electronic circuit.

[0102] Referring to FIG. 6, the noninvasive substance analysis method of the present embodiment has similar steps to the noninvasive substance analysis method of embodiment 1, but differs from the noninvasive substance analysis method of embodiment 1 mainly in the following points.

[0103] In step S2 of the present embodiment, similarly to step S2 of embodiment 1, the excitation light source 20 may not emit the excitation light 21. Alternatively, in step S2 of the present embodiment, the excitation light source 20 may emit the excitation light 21, and the first optical shutter 35 and the second optical shutter 36 may block the excitation light 21.

[0104] In step S3 of this embodiment, the first optical shutter 35 passes the first excitation light 21a, and the second optical shutter 36 blocks the first excitation light 21a. The sample 18 is illuminated with the first excitation light 21a, but the reference material 19 is not illuminated with the first excitation light 21a.

[0105] In step S4 of the present embodiment, the first optical shutter 35 passes the second excitation light 21b, and the second optical shutter 36 blocks the second excitation light 21b. The sample 18 is illuminated with the second excitation light 21b, but the reference material 19 is not illuminated with the second excitation light 21b.

[0106] In step S5 of the present embodiment, the second optical shutter 36 passes the first excitation light 21a, and the first optical shutter 35 blocks the first excitation light 21a. The reference material 19 is illuminated with the first excitation light 21a, but the sample 18 is not illuminated with the first excitation light 21a.

[0107] In step S6 of the present embodiment, the second optical shutter 36 passes the second excitation light 21b, and the first optical shutter 35 blocks the second excitation light 21b. The reference material 19 is illuminated with the second excitation light 21b, but the sample 18 is not illuminated with the second excitation light 21b.

[0108] Noninvasive substance analysis apparatus 1 and noninvasive substance analysis method of the present embodiment provide the following advantages in addition to the advantages of noninvasive substance analysis apparatus 1 and noninvasive substance analysis method of embodiment 1.

[0109] In the non-invasive substance analysis device 1 of this embodiment, the optical path switch 30 includes a first optical shutter 35 arranged on the first optical path 24 and a second optical shutter 36 arranged on the second optical path 25.

[0110] Therefore, mechanical errors occurring when switching the optical path of the excitation light 21 (first excitation light 21a and second excitation light 21b) are reduced or eliminated. The analysis precision of the noninvasive substance analysis device 1 is improved. Also, the time required to switch the optical path of the excitation light 21 can be shortened. The analysis speed of the noninvasive substance analysis method of the noninvasive substance analysis device 1 is improved.

[0111] Embodiment 3 A noninvasive material analysis apparatus 1 according to the third embodiment will be described with reference to Fig. 12. The noninvasive material analysis apparatus 1 according to the present embodiment has a similar configuration to the noninvasive material analysis apparatus 1 according to the second embodiment, but differs mainly in the following respects.

[0112] In the non-invasive substance analysis device 1 of this embodiment, the first end face 13 and the second end face 14 are inclined with respect to the first main surface 11 and the second main surface 12. The probe light 41 is refracted at the first end face 13 and travels through the optical medium 10 toward the second main surface 12. The first mounting region 15 is irradiated with the probe light 41. The first irradiation region 24a may also be irradiated with the probe light 41. The probe light 41 is reflected at the first mounting region 15 and reflected at the first main surface 11. The second mounting region 16 is irradiated with the probe light 41. The second irradiation region 25a may also be irradiated with the probe light 41. The probe light 41 is reflected at the second mounting region 16 and exits from the second end face 14.

[0113] When the sample 18 and the reference material 19 are not irradiated with the excitation light 21 (the first excitation light 21a and the second excitation light 21b), the first refractive index gradient region 27 and the second refractive index gradient region 28 are not formed in the optical medium 10. In contrast, when the sample 18 is irradiated with the excitation light 21, the first refractive index gradient region 27 is formed in the optical medium 10. The probe light 41 is refracted in the first refractive index gradient region 27. When the reference material 19 is irradiated with the excitation light 21, the second refractive index gradient region 28 is formed in the optical medium 10. The probe light 41 is refracted in the second refractive index gradient region 28. Therefore, the positions 42b, 42c, 42d, and 42e of the probe light 41 are different from the position 42a of the probe light 41.

[0114] With reference to FIG. 6, the non-invasive substance analysis method of the present embodiment is the same as the non-invasive substance analysis method of the second embodiment.

[0115] Noninvasive substance analysis apparatus 1 and noninvasive substance analysis method of the present embodiment provide the following advantages in addition to the advantages of noninvasive substance analysis apparatus 1 and noninvasive substance analysis method of embodiment 1.

[0116] In the non-invasive substance analysis device 1 of this embodiment, the optical medium 10 includes a first main surface 11, a second main surface 12 opposite to the first main surface 11, a first end surface 13, and a second end surface 14 opposite to the first end surface 13. The first end surface 13 and the second end surface 14 are connected to the first main surface 11 and the second main surface 12, respectively. The excitation light 21 enters the optical medium 10 from the first main surface 11. The second main surface 12 includes a first mounting region 15 and a second mounting region 16. The probe light 41 enters the optical medium 10 from the first end surface 13, is reflected at the first main surface 11, the first mounting region 15, and the second mounting region 16, and exits from the second end surface 14.

[0117] This reduces the length of the optical path of probe light 41 passing near first mounting area 15. This reduces the effect of temperature fluctuations of sample 18 on the analysis results of the measurement target substance of sample 18. This improves the analytical accuracy of noninvasive substance analysis device 1 and noninvasive substance analysis method.

[0118] The embodiments 1 to 3 disclosed herein should be considered as illustrative and not restrictive in all respects. At least two of the embodiments 1 to 3 disclosed herein may be combined unless there is a contradiction. The scope of the present disclosure is indicated by the claims, not the above description, and is intended to include all modifications within the meaning and scope of the claims. [Explanation of symbols]

[0119] 1 Non-invasive substance analysis device, 10 Optical medium, 11 First main surface, 12 Second main surface, 13 First end surface, 14 Second end surface, 15 First mounting area, 16 Second mounting area, 18 Sample, 19 Reference material, 20 Excitation light source, 21 Excitation light, 21a First excitation light, 21b Second excitation light, 22 Light intensity modulator, 22c Controller, 23 Reflecting member, 24 First optical path, 24a First irradiation area, 25 Second optical path, 25a Second irradiation area, 27 First refractive index gradient area, 28 Second refractive index gradient area, 30 Optical path switcher, 31 Movable reflecting member, 32 Moving mechanism, 33 Beam splitter, 34 Reflecting member, 35 First optical shutter, 36 Second optical shutter, 37 Shutter controller, 40 Probe light source, 41 Probe light, 42a, 42b, 42c, 42d, 42e positions, 45 optical position detector, 46 lock-in amplifier, 47 multiplier, 48 low-pass filter, 50 analyzer, 51 displacement distance calculation unit, 52 analysis unit.

Claims

1. an optical medium including a first mounting region on which a sample is placed and a second mounting region on which a reference substance is placed; an excitation light source that emits a first excitation light; a probe light source that emits a probe light that travels through the optical medium; a light position detector that detects a position of the probe light emitted from the optical medium; and an optical path switcher; the optical path switch switches an optical path of the first excitation light between a first optical path and a second optical path, the first placement area is irradiated with the first excitation light traveling through the first optical path, and the second placement area is irradiated with the first excitation light traveling through the second optical path; The light position detector detects a first position of the probe light when the sample and the reference substance are not irradiated with the first excitation light, a second position of the probe light when the first excitation light travels along the first optical path, and a third position of the probe light when the first excitation light travels along the second optical path.

2. Further comprising an analyzer; The non-invasive substance analysis device according to claim 1 , wherein the analyzer analyzes the measurement target substance of the sample based on the first position, the second position, and the third position.

3. The analyzer includes a displacement distance calculation unit and an analysis unit, the displacement distance calculation unit calculates a first displacement distance of the probe light, which is a difference between the second position and the first position, and a second displacement distance of the probe light, which is a difference between the third position and the first position; The noninvasive substance analyzing device according to claim 2 , wherein the analysis section analyzes the substance to be measured based on the first displacement distance and the second displacement distance.

4. the excitation light source emits a second excitation light having a wavelength different from the first excitation light, the optical path switcher switches an optical path of the second excitation light between the first optical path and the second optical path, the first placement area is irradiated with the second excitation light traveling through the first optical path, and the second placement area is irradiated with the second excitation light traveling through the second optical path; the light position detector detects the first position of the probe light when the sample and the reference material are not illuminated with the first excitation light and the second excitation light; 2. The non-invasive substance analysis device of claim 1, wherein the light position detector further detects a fourth position of the probe light when the second excitation light travels along the first light path, and a fifth position of the probe light when the second excitation light travels along the second light path.

5. Further comprising an analyzer; The non-invasive substance analysis device according to claim 4 , wherein the analyzer analyzes the measurement target substance of the sample based on the first position, the second position, the third position, the fourth position, and the fifth position.

6. The analyzer includes a displacement distance calculation unit and an analysis unit, the displacement distance calculation unit calculates a first displacement distance of the probe light which is a difference between the second position and the first position, a second displacement distance of the probe light which is a difference between the third position and the first position, a third displacement distance of the probe light which is a difference between the fourth position and the first position, and a fourth displacement distance of the probe light which is a difference between the fifth position and the first position; The noninvasive substance analysis device according to claim 5 , wherein the analysis section analyzes the substance to be measured based on the first displacement distance, the second displacement distance, the third displacement distance, and the fourth displacement distance.

7. The noninvasive substance analyzing device according to claim 1 , wherein the optical path switcher includes a movable reflecting member and a moving mechanism that moves the movable reflecting member.

8. The noninvasive substance analyzing device according to claim 1 , wherein the optical path switcher includes a moving mechanism that moves the excitation light source.

9. 7. The noninvasive substance analysis device according to claim 1, wherein the optical path switcher includes a first optical shutter disposed on the first optical path and a second optical shutter disposed on the second optical path.

10. the optical medium includes a first main surface, a second main surface opposite to the first main surface, a first end surface, and a second end surface opposite to the first end surface, the first end surface and the second end surface being connected to the first main surface and the second main surface, respectively; the first excitation light is incident on the optical medium from the first principal surface, the second main surface includes the first mounting area and the second mounting area, 7. The noninvasive substance analysis device according to claim 1, wherein the probe light enters the optical medium from the first end face and exits from the second end face without being reflected by the first principal surface and the second principal surface.

11. the optical medium includes a first main surface, a second main surface opposite to the first main surface, a first end surface, and a second end surface opposite to the first end surface, the first end surface and the second end surface being connected to the first main surface and the second main surface, respectively; the first excitation light is incident on the optical medium from the first principal surface, the second main surface includes the first mounting area and the second mounting area, 7. The noninvasive substance analysis device according to claim 1, wherein the probe light enters the optical medium from the first end face, is reflected at the first main surface, the first mounting region, and the second mounting region, and exits from the second end face.

12. placing a sample and a reference material on a first and a second mounting area of ​​an optical medium, respectively; detecting a first position of the probe light exiting the optical medium without irradiating the sample and the reference substance with a first excitation light; irradiating the sample with the first excitation light and detecting a second position of the probe light exiting the optical medium; irradiating the reference material with the first excitation light by switching an optical path of the first excitation light, and detecting a third position of the probe light emitted from the optical medium; and analyzing the measured substance of the sample based on the first position, the second position, and the third position.

13. Analyzing the target substance to be measured Calculating a first displacement distance of the probe light, which is a difference between the second position and the first position, and a second displacement distance of the probe light, which is a difference between the third position and the first position; The non-invasive substance analysis method according to claim 12 , further comprising: analyzing the substance to be measured based on the first displacement distance and the second displacement distance.

14. irradiating the sample with second excitation light having a wavelength different from that of the first excitation light, and detecting a fourth position of the probe light exiting the optical medium; and detecting a fifth position of the probe light emitted from the optical medium by irradiating the reference substance with the second excitation light by switching an optical path of the second excitation light. the first position is detected without irradiating the first excitation light and the second excitation light, The non-invasive substance analysis method according to claim 12 , wherein the measurement target substance is analyzed based on the first position, the second position, the third position, the fourth position, and the fifth position.

15. Analyzing the target substance to be measured calculating a first displacement distance of the probe light, which is a difference between the second position and the first position, a second displacement distance of the probe light, which is a difference between the third position and the first position, a third displacement distance of the probe light, which is a difference between the fourth position and the first position, and a fourth displacement distance of the probe light, which is a difference between the fifth position and the first position; The non-invasive substance analysis method according to claim 14, further comprising: analyzing the substance to be measured based on the first displacement distance, the second displacement distance, the third displacement distance, and the fourth displacement distance.

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