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

Abstract

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

Description

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

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

[0002] Japanese Patent Publication No. 2017-519214 (Patent Document 1) discloses a non-invasive analysis system including an optical medium, an excitation light source, a probe light source, and a photodiode.

[0003] Special table 2017-519214 publication

[0004] However, in the noninvasive analysis system disclosed in Patent Document 1, when a substance to be measured is analyzed continuously over a long period of time using the noninvasive analysis system, the analysis conditions may 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 consideration of the above-mentioned problems, and its purpose is to provide a noninvasive substance analysis device and a noninvasive substance analysis method that have improved analytical accuracy over a long period of time.

[0005] The non-invasive substance analysis device disclosed herein 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 where a sample is placed and a second mounting area where a reference material is placed. The excitation light source emits first excitation light. The probe light source emits probe light that travels 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 optical path of the first excitation light between the first optical path and the second optical path. The first mounting area is irradiated with the first excitation light that travels through the first optical path. The second mounting area is irradiated with the first excitation light that travels through the second optical 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] A non-invasive substance analysis method according to the present disclosure includes placing a sample and a reference substance on a first mounting region and a second mounting region of an optical medium, respectively, and detecting a first position of probe light emitted from the optical medium without irradiating the sample and the reference substance with first excitation light. The non-invasive substance analysis method according to this embodiment includes 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 according to this embodiment includes analyzing the analyte substance in the sample based on the first position, the second position, and the third position.

[0007] The non-invasive substance analysis device and non-invasive substance analysis method of the present disclosure have improved analytical accuracy over a long period of time.

[0008] 1 is a schematic diagram of a noninvasive substance analysis device according to a first embodiment. FIG. 2 is a schematic partially enlarged plan view of a noninvasive substance analysis device according to a first embodiment. FIG. 3 is a schematic partially enlarged view of a noninvasive substance analysis device according to a first embodiment. FIG. 4 is a circuit diagram of a lock-in amplifier. FIG. 5 is a block diagram explaining the functional configuration of an analyzer. FIG. 6 is a flowchart of a noninvasive substance analysis method according to the first to third embodiments. FIG. 7 is a flowchart of a step of analyzing a substance to be measured in the noninvasive substance analysis method according to the first to third embodiments. FIG. 8 is a flowchart of an example of a step of calculating the absorbance of a substance to be measured from a displacement distance. FIG. 9 is a schematic diagram of a noninvasive substance analysis device according to a first modified embodiment of the first embodiment. FIG. 10 is a schematic diagram of a noninvasive substance analysis device according to a second modified embodiment of the first embodiment. FIG. 11 is a schematic diagram of a noninvasive substance analysis device according to a third embodiment.

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

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

[0011] The non-invasive substance analyzing device 1 mainly includes an optical medium 10, an excitation light source 20, a light path switcher 30, a probe light source 40, a light position detector 45, and an analyzer 50. The non-invasive substance analyzing device 1 may further include an optical intensity modulator 22, a controller 22c, and a lock-in amplifier 46. The non-invasive substance analyzing device 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 the first main surface 11, a first end surface 13, and a second end surface 14 opposite 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 for excitation light 21. The second main surface 12 includes a first mounting region 15 on which a sample 18 is placed and a second mounting region 16 on which a reference substance 19 is placed. The first end surface 13 is, for example, an incident surface for probe light 41. The second end surface 14 is, for example, an exit surface for 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 for the excitation light 21 and the probe light 41 is 25% or more. The optical transmittance of the optical medium 10 for 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 contains a substance to be measured. The substance to be measured is, for example, a biological component. The biological component is, for example, blood sugar, protein, amino acids, sugars, fatty acids, hormones, or neurotransmitters. The substance to be measured is on the surface of the sample 18 or inside the sample 18. The sample 18 may be a solution containing the substance to be measured. The sample 18 may further contain a substance not to be measured. For example, when the sample 18 is an aqueous solution of the substance to be measured, the substance not to be measured is water.

[0015] The reference material 19 has absorbance that is almost independent of changes in the surrounding environment (such as ambient 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, which will be 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 longer. The wavelength of the excitation light 21 may be, for example, 8.0 μm or longer. The wavelength of the excitation light 21 is, for example, 13.0 μm or shorter. The wavelength of the excitation light 21 may be, for example, 11.0 μm or shorter. For example, when measuring a patient's blood glucose level using the noninvasive substance analyzer 1, the wavelength range of the excitation light 21 is a wavelength range that includes wavelengths of the sugar fingerprint spectrum (for example, a wavelength range of 8.5 μm or longer and 10 μm or shorter). The excitation light source 20 is, for example, a quantum cascade laser that can emit broadband infrared light.

[0017] The excitation light source 20 may be a wavelength-tunable light source such as a wavelength-tunable laser. The excitation light 21 may be light having multiple 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 measurement light, and the first wavelength is the measurement wavelength. The first wavelength is, for example, the peak wavelength of the absorption spectrum of the substance to be measured in the sample 18. The second excitation light 21b is reference light, and the second wavelength is the 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 sends a drive signal having a modulation frequency f to the light intensity modulator 22, causing the light intensity modulator 22 to modulate the 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 blades (not shown) and a rotating mechanism (not shown) that rotates the blades. 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. Since the components in the interstitial fluid change in conjunction with the components in the blood, 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 interstitial fluid at a depth of several tens of μm from the surface of the sample 18, the modulation frequency f is set to be equal to or greater than 5 Hz and equal to or less than 100 Hz.

[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 optical path switcher 30 switches the optical path of the excitation light 21 between a first optical path 24 and a second optical path 25. The first mounting area 15 is irradiated with the excitation light 21 traveling through the first optical path 24. The second mounting area 16 is irradiated with the excitation light 21 traveling through the second optical path 25. The optical 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 optical 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 optical 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 optical path switch 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 along the first optical path 24. The first irradiation area 24a is an area of ​​the second main surface 12 that is irradiated with the excitation light 21 traveling along the first optical path 24. The first irradiation area 24a is located inside the first placement area 15. The sample 18 is irradiated with the excitation light 21 traveling along the first optical path 24. The second irradiation area 25a is irradiated with the excitation light 21 traveling along the second optical path 25. The second irradiation area 25a is an area of ​​the second main surface 12 that is irradiated with the excitation light 21 traveling along the second optical path 25. The second irradiation area 25a is an area of ​​the second main surface 12 that is irradiated with the excitation light 21 traveling along the second optical path 25. The second irradiation area 25a is located 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. The 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 generated within the optical medium 10, and a first refractive index gradient region 27 is generated within the optical medium 10.

[0024] The excitation light 21 traveling along the second optical path 25 is absorbed by the reference material 19. The 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 generated within the optical medium 10, and a second refractive index gradient region 28 is generated within the optical medium 10.

[0025] 1, the probe light source 40 emits 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 by the first main surface 11 or the second main surface 12, passes through a portion of the optical medium 10 close to the second main surface 12, and exits from the second end face 14. As shown in FIG. 2 , in a plan view of the first mounting region 15 or the second main surface 12, the optical path of the probe light 41 overlaps the first mounting region 15 and the second mounting region 16, as well as the first irradiation region 24 a and the second irradiation region 25 a. While the probe light 41 travels through the optical medium 10, the probe light 41 travels through a first refractive index gradient region 27 generated in the optical medium 10 by heat absorption by the sample 18, or a second refractive index gradient region 28 generated in the optical medium 10 by heat absorption 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 propagation direction of the probe light 41 due to the first refractive index gradient region 27 and the second refractive index gradient region 28 is large. This improves the accuracy of analyzing the target substance in the sample 18. For example, the beam diameter of the excitation light 21 is approximately 100 μm, and the beam diameter of the probe light 41 is approximately 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. 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 (first excitation light 21a and second excitation light 21b). 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. 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. 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. 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 (first excitation light 21a and 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 (first excitation light 21a and 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 of the probe light 41 on the light position detector 45 (positions 42b, 42c, 42d, and 42e) 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 via 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 optical intensity modulator 22 modulates the light intensity of the excitation light 21 at a modulation frequency f, the light position signals have a modulation frequency f.

[0032] 1, the lock-in amplifier 46 is connected to the controller 22c of the optical intensity modulator 22 and the light 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, out of the light position signals output from the light position detector 45. This removes noise contained in the light position signal output from the light position detector 45.

[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 having a modulation frequency f, which is output from the controller 22c to the optical intensity modulator 22. 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, multiplying the light position signal by the drive signal of the controller 22c 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 light position signal is removed.

[0034] Referring to FIG. 1 , the analyzer 50 analyzes the analyte substance of the sample 18 based on the positions 42a-42e. The analyzer 50 is, for example, a microcomputer including a processor and a storage device such as a random access memory (RAM) and a read-only memory (ROM). The processor may be, for example, a central processing unit (CPU). The RAM functions as a working memory that temporarily stores data processed by the processor. The storage device stores, for example, programs executed by the processor. In this embodiment, the analyzer 50 analyzes the analyte substance of the sample 18 by having the processor execute the programs stored in the storage device. The various processes in the analyzer 50 are not limited to being executed by software, but may also be realized by dedicated hardware (electronic circuits).

[0035] Referring 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 positions 42b and 42a, from the first light position signal representing position 42a and the second light position signal representing position 42b. The displacement distance calculation unit 51 calculates a displacement distance ΔD2 (see FIG. 3 ), which is the difference between positions 42c and 42a, from the first light position signal representing position 42a and the third light position signal representing position 42c. The displacement distance calculation unit 51 calculates a displacement distance ΔD3 (see FIG. 3 ), which is the difference between positions 42d and 42a, of the probe light 41, from the first light position signal representing position 42a and the fourth light position signal representing position 42d. The displacement distance calculation unit 51 calculates the displacement distance ΔD4 (see Figure 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 in 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 Figures 6 and 7. Referring to Figure 6, a sample 18 and a 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 (first excitation light 21a and 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 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 first excitation light 21a. The first excitation light 21a has a first wavelength. The first excitation light 21a is measurement light, and the first wavelength is the measurement wavelength. The first wavelength is, for example, the peak wavelength of the absorption spectrum of the substance to be measured. The optical 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, switching 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 principal 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, while the reference material 19 is not illuminated with the first excitation light 21a.

[0042] The first excitation light 21a traveling along 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 absorption heat in the sample 18. The absorption heat in the sample 18 is conducted to the optical medium 10. A first temperature gradient region is generated within the optical medium 10, and a first refractive index gradient region 27 is generated within 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 light 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, and the position 42c of the probe light 41 is detected (step S4). Step S4 is similar to step S3, except that 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 second excitation light 21b. The second excitation light 21b modulated by the optical intensity modulator 22 travels along a first optical path 24. The sample 18 is irradiated with the second excitation light 21b. The second excitation light 21b is absorbed by a substance not to be measured in the sample 18. The substance to be measured in the sample 18 does not absorb the second excitation light 21b. Absorption of the second excitation light 21b by the substance not to be measured generates absorption heat in the sample 18. The absorption heat in the sample 18 is conducted to the optical medium 10. A first temperature gradient region is generated within the optical medium 10, creating a first refractive index gradient region 27 within the optical medium 10. 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 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 the position 42c differs from the 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, except that 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 movement mechanism 32 moves the movable reflecting member 31 to a second position to switch the optical path of the excitation light 21 to a second optical path 25. The first excitation light 21a travels along 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 along 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 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 incident 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, and the position 42e of the probe light 41 is detected (step S6). Step S6 is similar to step S5, except that 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 second excitation light 21b. The second excitation light 21b modulated by the optical intensity modulator 22 travels along a 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 within the optical medium 10, and a second refractive index gradient region 28 is generated within the optical medium 10. 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 42e of the probe light 41. The position 42e is different from the position 42a.

[0050] The light position detector 45 outputs light position signals representing the incident positions (positions 42a-42e) of the probe light 41 on the light position detector 45 to the analyzer 50 via 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 optical 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. The lock-in amplifier 46 removes noise contained in the light position signals and amplifies the signals.

[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 a drive signal having a modulation frequency f that is output from the controller 22c to the optical intensity modulator 22. 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 from 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 sample 18 is analyzed for the substance to be measured based on the positions 42a-42e (step S7).

[0053] Specifically, analyzer 50 receives the optical position signals from which noise has been removed in lock-in amplifier 46. As previously described, the optical position signals include a first optical position signal representing position 42a, a second optical position signal representing position 42b, a third optical position signal representing position 42c, a fourth optical position signal representing position 42d, and a fifth optical position signal representing 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 analyte substance in the sample 18 and the absorbance of the non-analyte substance in 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 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 (step S12). ΔD2 is proportional to the absorbance of the non-target substance in 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 the 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 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 target substance at the measurement wavelength based on the displacement distances ΔD1, ΔD2, ΔD3, and ΔD4. An example of step S15 in which the absorbance of the 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 target substance of the sample 18 at the first wavelength of the first excitation light 21a will be described below with reference to FIG. 8.

[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). Both displacement distances ΔD1 and ΔD3 are 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 analyte substance in the sample 18 at the first wavelength and the absorbance of the non-analyte substance in 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 substance to be measured at the first wavelength of the first excitation light 21a and the absorbance of the substance not to be measured 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). Both displacement distances ΔD2 and ΔD4 are obtained by the second excitation light 21b having the second wavelength. As already described, ΔD2 is proportional to the absorbance of the non-target substance in 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-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-target substance at the first wavelength of the first excitation light 21a is equal to the absorbance of the non-target substance at the second wavelength of the second excitation light 21b, the absorbance of the target 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 way, the 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. The 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 in the sample 18 by the 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 intensity of excitation light 21, drift in the irradiation position of excitation light 21, and drift in the intensity of probe light 41 cause changes in the incident position of probe light 41 on light position detector 45. Therefore, drift phenomena reduce the accuracy of analysis of the target substance by noninvasive substance analysis device 1. Note that, in this specification, drift refers to gradual changes in ambient temperature, the intensity of excitation light 21, the irradiation position of excitation light 21, the intensity of probe light 41, etc., over long periods of use of noninvasive substance analysis device 1.

[0064] In this embodiment, a sample 18 and a reference substance 19 are placed on the optical medium 10. By switching the optical path of the excitation light 21, either the sample 18 or the reference substance 19 is irradiated with 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 significant change in the incident position of the probe light 41 occurs due to the drift phenomenon. Therefore, the influence of the drift phenomenon on the analysis results of the substance to be measured in the sample 18 can be eliminated. The analytical accuracy of the noninvasive substance analyzer 1 is improved over a long period of time.

[0065] Furthermore, the sample 18 often contains both a target substance and a non-target substance. The excitation light 21 is absorbed by the target substance and the non-target substance, causing both substances to generate heat. The heat from the target substance and the non-target substance forms the first refractive index gradient region 27. The non-target substance reduces the analytical accuracy of the target substance. In this embodiment, the sample 18 and the reference substance 19 are irradiated with second excitation light 21b having a second wavelength that is hardly absorbed by the target substance. Therefore, the influence of the non-target substance on the analytical results of the target substance in the sample 18 can be eliminated by using 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] 9 , in a first modification 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 22 c 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 variations 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 analyte substance in the sample 18. Furthermore, if the sample 18 does not contain any non-analyte substances, or if the absorption of the first excitation light 21a by the non-analyte substances is negligible compared to the absorption of the first excitation light 21a by the analyte substance, the excitation light source 20 may not emit the second excitation light 21b, steps S4 and S6 may be omitted, the analyte substance may be analyzed based on the positions 42a, 42b, and 42d in step S7, and the analyte may be analyzed based on the displacement distances ΔD1 and 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 the difference between the phase of the light position signal output from the light position detector 45 and the phase of the drive signal for the optical intensity modulator 22 output from the controller 22c.

[0070] The effects of the noninvasive substance analysis device 1 of this embodiment will be described. The noninvasive 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 in which a sample 18 is placed and a second mounting area 16 in 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 that travels 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 a first light path 24 and a 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 placement area 16 is irradiated with the first excitation light 21 a traveling through the second optical path 25. The light position detector 45 detects a first position (position 42 a) of the probe light 41 when the sample 18 and the reference substance 19 are not irradiated with the first excitation light 21 a, a second position (position 42 b) of the probe light 41 when the first excitation light 21 a travels through the first optical path 24, and a third position (position 42 d) of the probe light 41 when the first excitation light 21 a travels through the second optical path 25.

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

[0072] Furthermore, simply by switching the optical path of the first excitation light 21a, the second position (position 42b) and the third position (position 42d) of the probe light 41 can be detected. This allows the effects of drift to be more quickly and accurately removed from the analysis results of the target substance in the sample 18. This improves the analytical accuracy and speed of the noninvasive substance analyzer 1.

[0073] 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), and the third position (position 42d).

[0074] Therefore, the influence of the drift phenomenon can be eliminated from the analysis results of the measurement target substance of the sample 18. The analytical accuracy of the non-invasive 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 unit 51 and an analysis unit 52. The displacement distance calculation unit 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 unit 52 analyzes the measurement target substance based on the first displacement distance and the second displacement distance.

[0076] Therefore, the influence of the drift phenomenon can be eliminated from the analysis results of the measurement target substance of the sample 18. The analytical accuracy of the non-invasive substance analysis device 1 is improved over a long period of time.

[0077] In the noninvasive substance analyzing device 1 of this embodiment, the excitation light source 20 emits second excitation light 21b having a wavelength different from that of 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, the influence of the non-target substances on the analysis results of the target substance in sample 18 can be eliminated, thereby improving the analytical accuracy of non-invasive substance analyzer 1 over a long period of time.

[0079] The noninvasive substance analyzing 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, the influence of the non-target substances on the analysis results of the target substance in sample 18 can be eliminated, thereby improving the analytical accuracy of non-invasive substance analyzer 1 over a long period of time.

[0081] In the noninvasive substance analyzing device 1 of this embodiment, the analyzer 50 includes a displacement distance calculation unit 51 and an analysis unit 52. The displacement distance calculation unit 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), 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, a third displacement distance (displacement distance ΔD2) of the 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 the probe light 41, which is the difference between the fifth position (position 42e) and the first position. The analysis unit 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, the influence of the non-target substances on the analysis results of the target substance in sample 18 can be eliminated, thereby improving the analytical accuracy of non-invasive substance analyzer 1 over a long period of time.

[0083] In the non-invasive substance analyzing device 1 of this embodiment, the optical 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 analytical accuracy and analytical speed of the noninvasive substance analyzing device 1 are improved.

[0085] In the non-invasive substance analyzing 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 analytical accuracy and analytical speed of the noninvasive substance analyzing device 1 are improved.

[0087] In the noninvasive substance analyzing device 1 of this embodiment, the optical medium 10 includes a first main surface 11, a second main surface 12 opposite the first main surface 11, a first end surface 13, and a second end surface 14 opposite 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 or the second main surface 12.

[0088] The first mounting area 15 and the second mounting area 16 are both 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 this 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 ambient temperature drift, light intensity drift of the excitation light 21, drift of the irradiation position of the excitation light 21, and light intensity drift of the probe light 41 from the analysis results of the measurement target substance in the sample 18. This improves the analytical accuracy of the non-invasive substance analysis method over a long period of time.

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

[0092] In the non-invasive 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 and 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 eliminated from the analysis results of the measurement target substance in 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 second excitation light 21b having a wavelength different from that of the first excitation light 21a and detecting a fourth position (position 42c) of the probe light 41 emitted from the optical medium 10 (step S4), and irradiating the reference material 19 with the second excitation light 21b by switching the optical path of the second excitation light 21b and detecting 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 reference material 19 with the first excitation light 21a and the second excitation light 21b. The substance to be measured 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, the influence of the non-target substances on the analysis results of the target substance in sample 18 can be eliminated, thereby improving the analytical accuracy of the non-invasive substance analysis method over a long period of time.

[0096] In the non-invasive 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, the influence of the non-target substances on the analysis results of the target substance in sample 18 can be eliminated, thereby improving the analytical accuracy of the non-invasive substance analysis method over a long period of time.

[0098] Embodiment 2 A noninvasive substance analysis device 1 of embodiment 2 will be described with reference to Figure 11. The noninvasive substance analysis device 1 of this embodiment has a similar configuration to the noninvasive substance analysis device 1 of embodiment 1, but differs mainly in the following respects.

[0099] In the non-invasive substance analyzing 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 (first excitation light 21a and second excitation light 21b) into a first beam that travels along a first optical path 24 and a second beam that travels along a 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 them. The shutter controller 37 switches the first optical shutter 35 between an open state that passes the excitation light 21 traveling along the first optical path 24 and a closed state that blocks the excitation light 21 traveling along the first optical path 24. The shutter controller 37 switches the second optical shutter 36 between an open state that passes the excitation light 21 traveling along the second optical path 25 and a closed state that blocks the excitation light 21 traveling along the second optical path 25. The shutter controller 37 is, for example, a microcomputer or an electronic circuit.

[0102] Referring to FIG. 6, the non-invasive substance analysis method of this embodiment includes steps similar to those of the non-invasive substance analysis method of embodiment 1, but differs from the non-invasive substance analysis method of embodiment 1 mainly in the following respects.

[0103] In step S2 of the present embodiment, similar 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 21 a, and the second optical shutter 36 blocks the first excitation light 21 a. The sample 18 is illuminated with the first excitation light 21 a, but the reference material 19 is not illuminated with the first excitation light 21 a.

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

[0107] In step S6 of this 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 irradiated with the second excitation light 21b, but the sample 18 is not irradiated with the second excitation light 21b.

[0108] The non-invasive substance analyzing device 1 and the non-invasive substance analyzing method of this embodiment have the following advantages in addition to the advantages of the non-invasive substance analyzing device 1 and the non-invasive substance analyzing method of the first embodiment.

[0109] In the non-invasive substance analysis device 1 of this embodiment, the optical path switcher 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] This reduces or eliminates mechanical errors that occur when switching the optical path of the excitation light 21 (first excitation light 21a and second excitation light 21b), improving the analytical accuracy of the noninvasive substance analysis device 1. Furthermore, the time required to switch the optical path of the excitation light 21 can be reduced, improving the analytical speed of the noninvasive substance analysis method using the noninvasive substance analysis device 1.

[0111] Embodiment 3 A noninvasive substance analysis device 1 according to embodiment 3 will be described with reference to Figure 12. The noninvasive substance analysis device 1 according to this embodiment has a similar configuration to the noninvasive substance analysis device 1 according to embodiment 2, but differs mainly in the following respects.

[0112] In the noninvasive 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 by the first mounting region 15 and then by 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 by the second mounting region 16 and exits from the second end face 14.

[0113] When the sample 18 and the reference substance 19 are not irradiated with the excitation light 21 (first excitation light 21a and 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 substance 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, positions 42b, 42c, 42d, and 42e of the probe light 41 are different from position 42a of the probe light 41.

[0114] Referring 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] The non-invasive substance analyzing device 1 and the non-invasive substance analyzing method of this embodiment have the following advantages in addition to the advantages of the non-invasive substance analyzing device 1 and the non-invasive substance analyzing method of the first embodiment.

[0116] In the noninvasive substance analyzing device 1 of this embodiment, the optical medium 10 includes a first main surface 11, a second main surface 12 opposite the first main surface 11, a first end surface 13, and a second end surface 14 opposite 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. 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. Probe light 41 enters the optical medium 10 from the first end surface 13, is reflected by 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 the probe light 41 passing near the first placement area 15. This reduces the effect of temperature fluctuations of the sample 18 on the analysis results of the measurement target substance of the sample 18. This improves the analytical accuracy of the noninvasive substance analysis device 1 and the noninvasive substance analysis method.

[0118] The presently disclosed embodiments 1 to 3 should be considered to be illustrative in all respects and not restrictive. Unless there is a contradiction, at least two of the presently disclosed embodiments 1 to 3 may be combined. The scope of the present disclosure is defined by the claims, not the above description, and is intended to include all modifications within the meaning and scope of the claims.

[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 substance, 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. A non-invasive substance analysis device comprising: an optical medium including a first mounting area on which a sample is placed and a second mounting area on which a reference substance is placed; an excitation light source that emits first excitation light; a probe light source that emits probe light that travels through the optical medium; a light position detector that detects the position of the probe light emitted from the optical medium; and a light path switcher, wherein the light path switcher switches the light path of the first excitation light between a first light path and a second light path, so that the first mounting area is irradiated with the first excitation light traveling through the first light path and the second mounting area is irradiated with the first excitation light traveling through the second light path; and 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 through the first light path, and a third position of the probe light when the first excitation light travels through the second light path.

2. The non-invasive substance analysis device according to claim 1, further comprising an analyzer, wherein the analyzer analyzes the substance to be measured in the sample based on the first position, the second position, and the third position.

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

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

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

6. The non-invasive substance analysis device according to claim 5, wherein the analyzer includes a displacement distance calculation unit and an analysis unit, wherein the displacement distance calculation unit calculates a first displacement distance of the probe light which is the difference between the second position and the first position, a second displacement distance of the probe light which is the difference between the third position and the first position, a third displacement distance of the probe light which is the difference between the fourth position and the first position, and a fourth displacement distance of the probe light which is the difference between the fifth position and the first position, and the analysis unit 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. A non-invasive substance analysis device according to any one of claims 1 to 6, wherein the optical path switcher includes a movable reflecting member and a movement mechanism for moving the movable reflecting member.

8. A non-invasive substance analysis device according to any one of claims 1 to 6, wherein the optical path switcher includes a movement mechanism for moving the excitation light source.

9. A non-invasive substance analysis device according to any one of claims 1 to 6, wherein the optical path switcher includes a first optical shutter arranged on the first optical path and a second optical shutter arranged on the second optical path.

10. A non-invasive substance analysis device according to any one of claims 1 to 9, wherein the optical medium includes a first main surface, a second main surface opposite the first main surface, a first end surface, and a second end surface opposite 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 enters the optical medium from the first main surface; the second main surface includes the first mounting area and the second mounting area; and the probe light enters the optical medium from the first end surface and exits from the second end surface without being reflected by the first main surface or the second main surface.

11. A non-invasive substance analysis device according to any one of claims 1 to 9, wherein the optical medium includes a first main surface, a second main surface opposite the first main surface, a first end surface, and a second end surface opposite 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 main surface; the second main surface includes the first mounting area and the second mounting area; and the probe light is incident on the optical medium from the first end surface, is reflected by the first main surface, the first mounting area, and the second mounting area, and is emitted from the second end surface.

12. A non-invasive substance analysis method comprising: placing a sample and a reference substance on a first placement area and a second placement area of ​​an optical medium, respectively; detecting a first position of probe light emitted from the optical medium without irradiating the sample and the reference substance with first excitation light; irradiating the sample with the first excitation light and detecting a second position of the probe light emitted from the optical medium; 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; and analyzing the substance to be measured in the sample based on the first position, the second position, and the third position.

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

14. A non-invasive substance analysis method as described in claim 12, further comprising: irradiating the sample with second excitation light having a different wavelength from the first excitation light, and detecting a fourth position of the probe light emerging from the optical medium; and irradiating the reference substance with the second excitation light by switching the optical path of the second excitation light, and detecting a fifth position of the probe light emerging from the optical medium, wherein the first position is detected without irradiating the first excitation light and the second excitation light; and the substance to be measured is analyzed based on the first position, the second position, the third position, the fourth position, and the fifth position.

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

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