Non-invasive material analysis device

Abstract

The non-invasive material analysis device (1) includes a sample support plate (10), an excitation light source (20), and temperature sensors (25, 26). The sample support plate (10) has a main surface (10a) including a sample placement area (12) and a main surface (10b) opposite to the main surface (10a). The temperature sensors (25, 26) are disposed on the main surface (10a). A through hole (13) extending from the sample placement area (12) to the main surface (10b) is disposed on the sample support plate (10). Excitation light (21) emitted from the excitation light source (20) is irradiated onto the sample (15) placed on the sample placement area (12) through the through hole (13).

Description

Technical Field

[0001] The present disclosure relates to a non-invasive material analysis device. Background Art

[0002] Japanese Patent Application Publication No. 2017-519214 (Patent Document 1) discloses a non-invasive analysis system having an optical medium, an infrared light source, a detection light source, and a photodiode. Specifically, a biological sample is placed on the optical medium. The infrared light source radiates infrared light. The infrared light is irradiated to the biological sample via the optical medium. The infrared light is absorbed by the biological sample, and the biological sample generates heat. The degree of heat absorption of the biological sample depends on the amount or concentration of the biological component in the sample or on the surface of the sample.

[0003] The detection light source radiates the detection light as visible light toward the optical medium. The detection light is totally reflected internally at the interface between the optical medium and the biological sample, and is emitted from the optical medium. The absorption heat of the biological sample is transferred to the optical medium, causing the refractive index of the optical medium to change. The change in the refractive index of the optical medium affects the total internal reflection of the detection light at the interface between the optical medium and the biological sample, causing the traveling direction of the detection light emitted from the optical medium to change. The photodiode functions as a light position sensor to detect the change in the traveling direction of the detection light. Based on the change in the traveling direction of the detection light detected by the photodiode, the amount or concentration of the biological component is measured. For example, when the sample is the patient's skin, the patient's blood sugar level is measured as a biological component.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application No. 2017-519214 Summary of the invention

[0007] However, in the non-invasive analysis system disclosed in Patent Document 1, the absorption heat of the biological sample quickly diffuses to the entire optical medium. Therefore, since the change in the traveling direction of the detection light caused by the absorption heat of the biological sample is small, it is impossible to accurately analyze the biological components in the sample or on the surface of the sample. The present disclosure is completed in view of the above-mentioned problems, and its purpose is to provide a non-invasive material analysis device that can more accurately analyze the substances in the sample or on the surface of the sample.

[0008] The non-invasive material analysis device disclosed in the present invention comprises a sample support plate, an excitation light source and a temperature sensor. The sample support plate has a first main surface including a sample loading area and a second main surface on the side opposite to the first main surface. The excitation light source radiates excitation light toward a sample loaded on the sample loading area. The temperature sensor is arranged on the first main surface. A through hole extending from the sample loading area to the second main surface is arranged on the sample support plate. The excitation light is irradiated to the sample through the through hole.

[0009] In the non-invasive material analysis device disclosed in the present invention, a through hole through which the excitation light passes is provided in the sample support plate. Therefore, the excitation light is not absorbed by the sample support plate, but reaches the sample with a stronger light intensity. The absorption heat of the sample increases. In addition, the absorption heat of the sample is difficult to dissipate in the thickness direction of the sample support plate (the direction in which the first main surface and the second main surface face each other). When the sample is irradiated with the excitation light, the temperature signal output from the temperature sensor becomes larger. Therefore, the substance in the sample or on the surface of the sample can be analyzed more accurately. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 This is a schematic top view of the non-invasive material analysis device according to the first embodiment.

[0011] Figure 2 The non-invasive substance analysis device of the first embodiment Figure 1 A schematic cross-sectional view taken along section line II-II is shown.

[0012] Figure 3 This is a schematic partial enlarged cross-sectional view of the non-invasive material analysis device according to the first embodiment.

[0013] Figure 4 This is the circuit diagram of a lock-in amplifier.

[0014] Figure 5 This is a diagram showing the flow of the non-invasive material analysis method according to the first embodiment.

[0015] Figure 6 It is a diagram showing the simulation results of the normalized temperature variation range of Example 1 and Comparative Examples 1-1 and 1-2.

[0016] Figure 7 This is a schematic cross-sectional view of a non-invasive material analysis device according to a modified example of the first embodiment.

[0017] Figure 8 This is a schematic cross-sectional view of a non-invasive material analysis device according to a second embodiment.

[0018] Fig. 9 It is a diagram showing the simulation results of the normalized temperature variation range of Example 2 and Comparative Examples 2-1 and 2-2.

[0019] Fig.10 This is a schematic top view of a non-invasive material analysis device according to a third embodiment.

[0020] Fig.11 The non-invasive material analysis device of the third embodiment Fig.10 A schematic cross-sectional view taken along section line XI-XI is shown.

[0021] Fig.12 This is a schematic top view of a non-invasive material analysis device according to a fourth embodiment.

[0022] Fig.13 The non-invasive material analysis device of the fourth embodiment Fig.12 A schematic cross-sectional view taken along section line XIII-XIII is shown.

[0023] Fig.14 This is a schematic top view of a non-invasive material analysis device according to a fifth embodiment.

[0024] Fig.15 The non-invasive material analysis device of the fifth embodiment Fig.14 A schematic cross-sectional view taken along section line XV-XV is shown.

[0025] Fig.16 This is a schematic top view of a non-invasive material analysis device according to a sixth embodiment.

[0026] Fig.17 The non-invasive material analysis device of embodiment 6 Fig.16 A schematic cross-sectional view taken along section line XVII-XVII is shown.

[0027] (Explanation of symbols)

[0028] 1, 1b, 1c, 1d, 1e, 1f: non-invasive material analysis device; 10: sample support plate; 10a, 10b: main surface; 11: substrate; 12: sample mounting area; 13: through hole; 13c: central axis; 14: low thermal conductivity film; 15: sample; 20: excitation light source; 21: excitation light; 21b: light irradiation area; 22: optical chopper; 23: beam splitter; 24: photodetector; 25, 26, 50: temperature sensor; 27: temperature sensor body ; 28: protective film; 30, 32: electrical wiring; 34: phase-locked amplifier; 35: multiplier; 36: low-pass filter; 37: signal processing unit; 38: material analysis unit; 40, 41: reference temperature sensor; 45: optical medium; 51: first optical waveguide; 51a, 51b: end; 52: waveguide type ring resonator; 53: second optical waveguide; 53a, 53b: end; 54: cladding; 55, 56: terminal; 58: detection light source; 59: light intensity detector. DETAILED DESCRIPTION

[0029] Hereinafter, the embodiment will be described. In addition, the same reference numerals are attached to the same structures, and the description thereof will not be repeated.

[0030] Implementation method 1.

[0031] Reference Figures 1 to 4 , the non-invasive material analysis device 1 according to the first embodiment is described. Figure 1 as well as Figure 2 The non-invasive material analysis device 1 includes a sample support plate 10 , an excitation light source 20 , an optical chopper 22 , temperature sensors 25 and 26 , a lock-in amplifier 34 , a signal processing unit 37 , and a material analysis unit 38 .

[0032] The sample support plate 10 has a main surface 10a and a main surface 10b on the opposite side of the main surface 10a. The main surface 10a includes a sample mounting area 12 for mounting a sample 15. The sample 15 is, for example, a biological sample such as a patient's finger, wrist, arm, earlobe or lip. In the present embodiment, the sample support plate 10 is composed of a substrate 11. The substrate 11 is formed of a material that is opaque to the excitation light 21. The substrate 11 is formed of, for example, plastic such as polyethylene, polycarbonate, polyurethane or acrylic resin, or glass.

[0033] The sample support plate 10 is provided with a through hole 13 extending from the sample placement region 12 to the main surface 10b. When the main surface 10a is viewed in plan, the size of the sample 15 is larger than the size of the through hole 13.

[0034] The excitation light source 20 radiates excitation light 21 toward the sample 15 placed on the sample placement area 12. The wavelength of the excitation light 21 is determined by the absorption wavelength of the substance in the sample 15 or on the surface of the sample 15. The excitation light 21 is, for example, mid-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 also 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 also be 11.0 μm or less. The excitation light 21 may also be light having multiple wavelengths. For example, when the non-invasive material analysis device 1 is used to measure the blood sugar level of a patient, 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 radiate broadband mid-infrared light. Reference light that is not absorbed by the substance in the sample 15 or on the surface of the sample 15 may also be irradiated to the sample 15 together with the excitation light 21.

[0035] The optical chopper 22 periodically modulates the intensity of the excitation light 21. The optical chopper 22 includes, for example, a plurality of rotating blades. The plurality of rotating blades are formed of a material that is opaque to the excitation light 21. When the excitation light 21 is cut off by one of the plurality of rotating blades, the sample 15 is not irradiated with the excitation light 21. In contrast, when the excitation light 21 passes between a pair of mutually adjacent rotating blades among the plurality of rotating blades, the sample 15 is irradiated with the excitation light 21. In this way, the optical chopper 22 modulates the intensity of the excitation light 21 emitted from the excitation light source 20. The optical chopper 22 sends a reference signal having the same frequency as the intensity modulation frequency of the intensity modulated excitation light 21 to the lock-in amplifier 34 via the electrical wiring 30.

[0036] The excitation light 21 modulated in intensity by the optical chopper 22 is incident on the sample support plate 10 from the main surface 10b side. The excitation light 21 is irradiated to the sample 15 via the through hole 13. The excitation light 21 advances, for example, on the central axis 13c of the through hole 13. When the excitation light 21 passes through the optical chopper 22, the excitation light 21 is irradiated to the sample 15. The excitation light 21 is absorbed by the substance in the sample 15 or on the surface of the sample 15. Since the excitation light 21 is absorbed by the substance in the sample 15 or on the surface of the sample 15, absorption heat is generated in the sample 15. In contrast, when the excitation light 21 is cut off by the optical chopper 22, the excitation light 21 is not irradiated to the sample 15, and absorption heat is not generated in the sample 15. Therefore, the temperature of the sample 15 changes at the intensity modulation frequency of the excitation light 21.

[0037] The substance in the sample 15 or on the surface of the sample 15 is, for example, a biological component. When the non-invasive substance analyzer 1 is used to obtain the blood sugar level of a patient, the substance analyzed by the non-invasive substance analyzer 1 is sugar present in the interstitial fluid in the epidermis of the patient.

[0038] The temperature sensors 25 and 26 are provided on the main surface 10a. The temperature sensors 25 and 26 are provided in the sample placement area 12. When the sample 15 is placed on the sample placement area 12, the temperature sensors 25 and 26 contact the sample 15 and detect the temperature of the sample 15. The temperature sensors 25 and 26 detect the temperature of the sample 15 and output a temperature signal corresponding to the temperature to the lock-in amplifier 34. Specifically, the temperature sensor 25 detects the temperature of the portion of the sample 15 that the temperature sensor 25 contacts and outputs a temperature signal corresponding to the temperature to the lock-in amplifier 34. The temperature sensor 26 detects the temperature of the portion of the sample 15 that the temperature sensor 26 contacts and outputs a temperature signal corresponding to the temperature to the lock-in amplifier 34.

[0039] The temperature of the sample 15 varies at the intensity modulation frequency of the excitation light 21, so the temperature signal output from the temperature sensors 25 and 26 also varies at the intensity modulation frequency of the excitation light 21. For example, the temperature sensors 25 and 26 output the minimum value of the temperature signal when the excitation light 21 is not irradiated to the sample 15, and output the maximum value of the temperature signal when the excitation light 21 is irradiated to the sample 15. The difference between the maximum value and the minimum value of the temperature signal is the amplitude of the temperature signal. The amplitude of the temperature signal of the temperature sensors 25 and 26 corresponds to the temperature variation amplitude of the sample 15 measured by the temperature sensors 25 and 26 in the analysis of the sample 15. In the present embodiment, the analysis of the sample 15 means the period during which the intensity-modulated excitation light 21 is irradiated to the sample 15.

[0040] The temperature sensors 25 and 26 are arranged near the through hole 13. For example, the distance d1 between each of the temperature sensors 25 and 26 and the through hole 13 is 50 μm or less. The distance d1 may be 20 μm or less or 10 μm or less. The distance d1 is 10% or less of the size of the through hole 13 (e.g., the diameter of the through hole 13). The distance d1 may also be 5% or less of the size of the through hole 13. When the main surface 10a is viewed from above, the temperature sensors 25 and 26 are arranged rotationally symmetrically with respect to the central axis 13c of the through hole 13.

[0041] Reference Figure 3 The temperature sensors 25 and 26 include a temperature sensor body 27 . The temperature sensors 25 and 26 may further include a protective film 28 .

[0042] The temperature sensor body 27 is, for example, a thermocouple, a thermopile, a thermistor, or a diode.

[0043] The thermocouple makes two dissimilar material sheets contact each other, and measures the temperature of the sample 15 based on the thermoelectromotive force generated at the contact part of the two dissimilar material sheets. The two material sheets constituting the thermocouple are formed of, for example, iron, copper-nickel alloy, copper, nickel-chromium alloy, nickel-aluminum alloy, nickel-silicon alloy, nickel-chromium-silicon alloy, platinum, platinum-rhodium alloy, bismuth, antimony, or a combination thereof. The two material sheets constituting the thermocouple can also be formed of p-type polysilicon and n-type polysilicon. A thermopile is formed by connecting a plurality of thermocouples.

[0044] The electrical resistance of the thermistor changes according to the temperature of the thermistor. The temperature of the sample 15 is detected according to the electrical resistance of the thermistor. The thermistor is preferably formed of a material with a large temperature resistance coefficient. The thermistor is formed of, for example, vanadium oxide, NiMoCo oxide, Ti, polycrystalline silicon, amorphous silicon, amorphous silicon germanium, MnO3 or YBaCuO.

[0045] The forward voltage of the diode changes according to the temperature of the diode. Based on the forward voltage of the diode, the temperature of the sample 15 is detected. The diode is, for example, a Si diode.

[0046] The protective film 28 covers the temperature sensor body 27. The protective film 28 prevents the sample 15 from contacting the temperature sensor body 27. The protective film 28 preferably has a low thermal conductivity (e.g., a thermal conductivity of 0.5 W / (m·K) or less) and a thin thickness (e.g., a thickness of 10 μm or less). Since the thermal conductivity of the protective film 28 is low, it is difficult for the absorbed heat of the sample 15 to diffuse rapidly to the entire sample support plate 10. Since the protective film 28 is thin, even if the thermal conductivity of the protective film 28 is low, the absorbed heat of the sample 15 is efficiently conducted to the temperature sensor body 27.

[0047] Reference Figure 2 The lock-in amplifier 34 is connected to the optical chopper 22 via the electrical wiring 30. The lock-in amplifier 34 receives a reference signal having the same frequency as the intensity modulation frequency of the intensity-modulated excitation light 21 from the optical chopper 22. Figure 1 as well as Figure 2 The lock-in amplifier 34 is connected to the temperature sensors 25 and 26 through the electrical wiring 32. The lock-in amplifier 34 receives a temperature signal corresponding to the temperature of the sample 15 from the temperature sensors 25 and 26. Specifically, the lock-in amplifier 34 receives a temperature signal corresponding to the temperature of the portion of the sample 15 in contact with the temperature sensor 25 from the temperature sensor 25. The lock-in amplifier 34 receives a temperature signal corresponding to the temperature of the portion of the sample 15 in contact with the temperature sensor 26 from the temperature sensor 26.

[0048] The lock-in amplifier 34 performs synchronous detection on the temperature signals received from the temperature sensors 25 and 26 using the reference signal received from the optical chopper 22. In this way, the lock-in amplifier 34 outputs the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26. The temperature variation amplitude signal of the temperature sensor 25 is a temperature variation amplitude signal corresponding to the temperature variation amplitude of the sample 15 measured by the temperature sensor 25 in the analysis of the sample 15. The temperature variation amplitude signal of the temperature sensor 26 is a temperature variation amplitude signal corresponding to the temperature variation amplitude of the sample 15 measured by the temperature sensor 26 in the analysis of the sample 15.

[0049] Reference Figure 4, the operation of the phase-locked amplifier 34 will be specifically described. The phase-locked amplifier 34 includes a multiplier 35 and a low-pass filter 36. The multiplier 35 multiplies the temperature signal of the temperature sensor 25 and the reference signal. The multiplier 35 outputs a DC component proportional to the amplitude of the temperature signal of the temperature sensor 25 and an AC component that varies at a frequency twice the intensity modulation frequency of the excitation light 21. The low-pass filter 36 removes the AC component and allows the DC component to pass. In this way, the phase-locked amplifier 34 outputs a DC component proportional to the amplitude of the temperature signal of the temperature sensor 25. The amplitude of the temperature signal of the temperature sensor 25 corresponds to the temperature variation amplitude of the portion of the sample 15 in contact with the temperature sensor 25 during the analysis of the sample 15. Therefore, the DC component is a temperature variation amplitude signal of the temperature sensor 25.

[0050] Similarly, the lock-in amplifier 34 outputs a DC component proportional to the amplitude of the temperature signal of the temperature sensor 26. The DC component is a temperature variation amplitude signal of the temperature sensor 26.

[0051] Reference Figure 1 as well as Figure 2 The signal processing unit 37 is connected to the lock-in amplifier 34. The signal processing unit 37 receives the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26 from the lock-in amplifier 34. The signal processing unit 37 calculates the average of the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26. The signal processing unit 37 outputs an average temperature variation amplitude signal corresponding to the average of the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26. The signal processing unit 37 is, for example, a microcomputer including a processor and a storage device. The signal processing unit 37 operates by the processor executing a program stored in the storage device.

[0052] The substance analysis unit 38 is connected to the signal processing unit 37. The substance analysis unit 38 receives the average temperature variation range signal from the signal processing unit 37. The substance analysis unit 38 analyzes a substance in the sample 15 or on the surface of the sample 15 based on the average temperature variation range signal.

[0053] For example, the material analysis unit 38 refers to a data table that corresponds the wavelength of the excitation light 21 to the type of the material and a data table that corresponds the size of the average temperature variation amplitude signal to the amount or concentration of the material, determines the type of the material in the sample 15 or on the surface of the sample 15, and calculates the amount or concentration of the material. The material analysis unit 38 is, for example, a microcomputer including a processor and a storage device. These data tables are stored in the storage device. The material analysis unit 38 operates by the processor executing the program stored in the storage device.

[0054] The thermal conductivity of the substrate 11 may be, for example, 5 W / (m·K) or less, 2 W / (m·K) or less, 1 W / (m·K) or less, or 0.3 W / (m·K) or less. Therefore, the absorption heat generated in the sample 15 due to the irradiation of the excitation light 21 to the sample 15 is difficult to quickly diffuse to the entire substrate 11, and the temperature variation amplitude signal of the temperature sensors 25 and 26 becomes larger. The substance in the sample 15 or on the surface of the sample 15 can be analyzed with higher accuracy.

[0055] The thermal conductivity of the substrate 11 is preferably lower than that of the sample 15. For example, when the sample 15 is human skin, the thermal conductivity of the sample 15 is about 0.5 W / (m·K). When the substrate 11 is formed of plastic, the thermal conductivity of the substrate 11 is 0.1 W / (m·K) or more and 0.3 W / (m·K) or less. Therefore, the absorption heat generated in the sample 15 due to the irradiation of the excitation light 21 to the sample 15 is difficult to quickly diffuse to the entire substrate 11, and the temperature variation amplitude signal of the temperature sensors 25 and 26 becomes larger. The substance in the sample 15 or on the surface of the sample 15 can be analyzed with higher accuracy.

[0056] The heat diffusion length L of the sample 15 for absorbing heat is given by equation (1).

[0057] [Formula 1]

[0058]

[0059] Here, f is the frequency of heat absorption of the sample 15 (the intensity modulation frequency of the excitation light 21 ), and α is the thermal diffusion coefficient of the sample 15 .

[0060] Referring to the above formula (1), in order to analyze substances present in sample 15 more than tens of μm away from the surface of sample 15 (such as sugar in interstitial fluid), the frequency of heat absorption of sample 15 (intensity modulation frequency of excitation light 21) is set to, for example, greater than 5 Hz and less than 100 Hz.

[0061] Main reference Figure 5 , a non-invasive material analysis method according to the present embodiment using the non-invasive material analysis apparatus 1 is described.

[0062] The non-invasive material analysis method of the present embodiment includes placing a sample 15 on a sample holding area 12 (S1). When there is a difference between the temperature of the sample support plate 10 and the temperature of the sample 15, heat transfer occurs between the sample support plate 10 and the sample 15. This heat transfer makes it difficult to detect the temperature variation amplitude signal and to analyze the substance in the sample 15 or on the surface of the sample 15. Therefore, until a thermal equilibrium state is achieved between the sample support plate 10 and the sample 15, step S2 described later is not performed. The achievement of the thermal equilibrium state between the sample support plate 10 and the sample 15 can be detected by using the temperature sensors 25 and 26. For example, when the change in the temperature signal of the temperature sensors 25 and 26 per unit time becomes less than a threshold value (for example, 0.1°C / minute), it is considered that a thermal equilibrium state is achieved between the sample support plate 10 and the sample 15, and step S2 is performed.

[0063] The non-invasive material analysis method of this embodiment includes irradiating the sample 15 with the excitation light 21 whose intensity is modulated by the optical chopper 22 (S2). The optical chopper 22 sends a reference signal having the same frequency as the intensity modulation frequency of the excitation light 21 to the lock-in amplifier 34 via the electrical wiring 30.

[0064] When the excitation light 21 passes through the optical chopper 22, the excitation light 21 is absorbed by a substance in the sample 15 or on the surface of the sample 15, and absorption heat is generated in the sample 15. In contrast, when the excitation light 21 is cut off by the optical chopper 22, absorption heat is not generated in the sample 15. Therefore, the temperature signal output from the temperature sensors 25 and 26 changes at the intensity modulation frequency of the excitation light 21.

[0065] The non-invasive material analysis method of the present embodiment includes obtaining a temperature variation range signal of the temperature sensor 25 and a temperature variation range signal of the temperature sensor 26 ( S3 ).

[0066] Specifically, the phase-locked amplifier 34 receives a reference signal from the optical chopper 22 and a temperature signal from the temperature sensor 25. The phase-locked amplifier 34 includes a multiplier 35 and a low-pass filter 36. The multiplier 35 multiplies the temperature signal of the temperature sensor 25 and the reference signal. The multiplier 35 outputs a DC component proportional to the amplitude of the temperature signal of the temperature sensor 25 and an AC component that varies at a frequency twice the intensity modulation frequency of the excitation light 21. The low-pass filter 36 removes the AC component and allows the DC component to pass. In this way, the phase-locked amplifier 34 outputs a DC component proportional to the amplitude of the temperature signal of the temperature sensor 25. The DC component is a temperature variation amplitude signal of the temperature sensor 25.

[0067] Similarly, the lock-in amplifier 34 outputs a DC component proportional to the amplitude of the temperature signal of the temperature sensor 26. The DC component is a temperature variation amplitude signal of the temperature sensor 26.

[0068] The non-invasive material analysis method of this embodiment has the step of obtaining the average of the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26 as the average temperature variation amplitude signal (S4). Specifically, the signal processing unit 37 receives the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26 from the lock-in amplifier 34. The signal processing unit 37 calculates the average of the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26 as the average temperature variation amplitude signal. The signal processing unit 37 outputs the average temperature variation amplitude signal to the material analysis unit 38.

[0069] The non-invasive material analysis method of this embodiment includes analyzing a material in the sample 15 or on the surface of the sample 15 based on the average temperature variation amplitude signal (S5). The material analysis unit 38 receives the average temperature variation amplitude signal from the signal processing unit 37. For example, the material analysis unit 38 refers to a data table that corresponds the wavelength of the excitation light 21 and the type of the material and a data table that corresponds the size of the average temperature variation amplitude signal and the amount or concentration of the material, determines the type of the material in the sample 15 or on the surface of the sample 15, and calculates the amount or concentration of the material.

[0070] Reference Figure 6 By comparing Example 1 of the present embodiment with Comparative Examples 1-1 and 1-2, the function of the non-invasive material analysis device 1 of the present embodiment is described.

[0071] In Example 1, the substrate 11 is formed of a material (such as plastic or glass) that does not transmit the excitation light 21. In addition, in Example 1, the diameter of the through hole 13 is 36 μm, and the diameter of the light irradiation area 21b of the excitation light 21 is 30 μm. Comparative Example 1-1 is the same as Example 1, but the through hole 13 is not formed in the substrate 11. Comparative Example 1-2 is the same as Comparative Example 1-1, but in Comparative Example 1-2, it is assumed that the transmittance of the substrate 11 with respect to the excitation light 21 is 100%. Figure 6 The normalized temperature variation amplitude is the temperature variation amplitude of each point on the main surface 10a of Example 1, Comparative Example 1-1, and Comparative Example 1-2, which is normalized by the temperature variation amplitude of the edge of the through hole 13 in the main surface 10a of Example 1. The temperature variation amplitude of each point on the main surface 10a is given by the difference between the temperature of each point on the main surface 10a when the sample 15 is not irradiated with the excitation light 21 and the temperature of each point on the main surface 10a when the sample 15 is irradiated with the excitation light 21.

[0072] In Example 1, a through hole 13 is provided in the sample support plate 10. Therefore, the excitation light 21 is not absorbed by the sample support plate 10, but reaches the sample 15 with a stronger light intensity. The absorption heat of the sample 15 increases. In addition, the thermal conductivity of the air in the through hole 13 (0.024 W / (m·K)) is lower than the thermal conductivity of the substrate 11 (for example, the thermal conductivity of plastic: about 0.1 W / (m·K) or more and about 0.3 W / (m·K), the thermal conductivity of glass: about 0.5 W / (m·K) or more and about 0.7 W / (m·K)). Therefore, the absorption heat of the sample 15 is difficult to dissipate in the thickness direction of the sample support plate 10 (the direction in which the main surface 10a and the main surface 10b face each other). The temperature variation range of the main surface 10a in the analysis of the sample 15 becomes larger. In Example 1, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0073] In contrast, in Comparative Example 1-1, the substrate 11 is formed of a material that does not transmit the excitation light 21. Therefore, the excitation light 21 does not reach the sample 15, and no absorption heat of the sample 15 is generated. The temperature variation range of the main surface 10a in the analysis of the sample 15 is zero. In Comparative Example 1-1, the substance in the sample 15 or on the surface of the sample 15 cannot be accurately analyzed.

[0074] In Comparative Example 1-2, it is assumed that the transmittance of the substrate 11 with respect to the excitation light 21 is 100%, and the excitation light 21 reaches the sample 15. Therefore, the temperature variation amplitude of the main surface 10a in the analysis of the sample 15 is not zero. However, in Comparative Example 1-2, the through hole 13 is not provided in the substrate 11. Therefore, in Comparative Example 1-2, compared with Example 1, the absorbed heat of the sample 15 diffuses rapidly in the thickness direction of the sample support plate 10 (the direction in which the main surface 10a and the main surface 10b face each other). The temperature variation amplitude of the main surface 10a in Comparative Example 1-2 is smaller than the temperature variation amplitude of the main surface 10a in Example 1. In Comparative Example 1-2, it is impossible to accurately analyze the substance in the sample 15 or on the surface of the sample 15.

[0075] (Variation Example)

[0076] The sample support plate 10 (substrate 11) may be formed of a material that is transparent to the excitation light 21. The number of the temperature sensors 25 and 26 may be three or more.

[0077] The temperature sensor 26 may be omitted, and the number of the temperature sensor 25 may be one. In this case, the signal processing unit 37 is omitted. The substance analysis unit 38 receives the temperature variation amplitude signal of the temperature sensor 25 from the lock-in amplifier 34. The substance analysis unit 38 analyzes the substance in the sample 15 or on the surface of the sample 15 based on the temperature variation amplitude signal of the temperature sensor 25. In step S3, the temperature variation amplitude signal of the temperature sensor 25 is obtained, and step S4 is omitted. In step S5, the substance in the sample 15 or on the surface of the sample 15 is analyzed based on the temperature variation amplitude signal of the temperature sensor 25.

[0078] like Figure 7 As shown, the non-invasive material analysis device 1 may also include a beam splitter 23 and a photodetector 24. The excitation light 21 intensity-modulated by the optical chopper 22 is incident on the beam splitter 23. The beam splitter 23 divides the excitation light 21 into the excitation light 21 toward the sample 15 and the excitation light 21 toward the photodetector 24. The beam splitter 23 allows a part of the excitation light 21 intensity-modulated by the optical chopper 22 to be incident on the photodetector 24. The photodetector 24 detects the intensity of the intensity-modulated excitation light 21. The photodetector 24 is, for example, a photodiode. The photodetector 24 is connected to a lock-in amplifier 34 via an electrical wiring 30. The photodetector 24 outputs a reference signal corresponding to the intensity of the intensity-modulated excitation light 21 to the lock-in amplifier 34.

[0079] according to Figure 7 The modified example shown can remove the influence of the variation in the intensity of the excitation light 21 from the temperature variation amplitude signals of the temperature sensors 25 and 26. Even if the intensity of the excitation light 21 varies, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0080] The effects of the non-invasive material analysis device 1 of the present embodiment will be described.

[0081] The non-invasive material analysis device 1 of this embodiment includes a sample support plate 10, an excitation light source 20, and at least one temperature sensor (for example, temperature sensors 25, 26). The sample support plate 10 has a first main surface (main surface 10a) including a sample loading area 12 and a second main surface (main surface 10b) on the side opposite to the first main surface. The excitation light source 20 radiates excitation light 21 toward a sample 15 loaded on the sample loading area 12. At least one temperature sensor is provided on the first main surface. A through hole 13 extending from the sample loading area 12 to the second main surface is provided on the sample support plate 10. The excitation light 21 is irradiated to the sample 15 via the through hole 13.

[0082] In the non-invasive material analysis device 1, the through hole 13 through which the excitation light 21 passes is provided in the sample support plate 10. Therefore, the excitation light 21 is not absorbed by the sample support plate 10, but reaches the sample 15 with a stronger light intensity. The absorption heat of the sample 15 increases. In addition, the absorption heat of the sample 15 is difficult to dissipate in the thickness direction of the sample support plate 10 (the direction in which the first main surface (main surface 10a) and the second main surface (main surface 10b) face each other). When the excitation light 21 is irradiated to the sample 15, the temperature signal output from at least one temperature sensor (for example, the temperature sensors 25, 26) becomes larger. Therefore, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0083] In the non-invasive material analysis device 1, a material that is opaque to the excitation light 21 can be used as the sample support plate 10 (substrate 11). The range of selection of the material of the sample support plate 10 (substrate 11) is expanded. As the material of the sample support plate 10 (substrate 11), a material that is opaque to the excitation light 21 but has low thermal conductivity (such as plastic or glass) is used, so that when the excitation light 21 is irradiated to the sample 15, the temperature signal output from at least one temperature sensor (such as temperature sensors 25, 26) becomes larger. Therefore, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0084] In the non-invasive material analyzer 1 of the present embodiment, at least one temperature sensor (for example, the temperature sensors 25 and 26 ) is provided in the sample placement area 12 and is in contact with the sample 15 .

[0085] Therefore, the absorbed heat of the sample 15 is efficiently conducted to at least one temperature sensor (e.g., temperature sensors 25 and 26). When the sample 15 is irradiated with the excitation light 21, the temperature signal output from the at least one temperature sensor increases. The substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0086] The non-invasive material analysis device 1 of this embodiment further includes a material analysis unit 38. The material analysis unit 38 analyzes a material in the sample 15 or on the surface of the sample 15 based on a temperature variation amplitude signal of at least one temperature sensor (e.g., temperature sensors 25 and 26). The temperature variation amplitude signal of at least one temperature sensor corresponds to the temperature variation amplitude of the sample 15 measured by the at least one temperature sensor during the analysis of the sample 15.

[0087] In the temperature variation amplitude signal, noise included in the temperature signal output from at least one temperature sensor (for example, temperature sensors 25 and 26) is removed, so that the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0088] The non-invasive material analysis device 1 of this embodiment further includes a signal processing unit 37 and a material analysis unit 38. The at least one temperature sensor is a plurality of temperature sensors 25 and 26. The signal processing unit 37 outputs an average of a plurality of temperature variation amplitude signals. The plurality of temperature variation amplitude signals respectively correspond to the temperature variation amplitudes of the sample 15 measured by the corresponding temperature sensors among the plurality of temperature sensors 25 and 26 in the analysis of the sample 15. The material analysis unit 38 analyzes the material in the sample 15 or on the surface of the sample 15 based on the average of the plurality of temperature variation amplitude signals.

[0089] In the temperature variation amplitude signal, the noise included in the temperature signal output from the temperature sensors 25 and 26 is removed. In addition, the average of the plurality of temperature variation amplitude signals reduces the deviation between the plurality of temperature variation amplitude signals. Therefore, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0090] In the non-invasive material analysis device 1 of the present embodiment, at least one temperature sensor (for example, temperature sensors 25 and 26) includes a temperature sensor body 27. The temperature sensor body 27 is a thermocouple, a thermopile, a thermistor, or a diode.

[0091] Therefore, there is no need for a probe light source for radiating probe light for measuring absorbed heat of the sample 15 and an optical position sensor for detecting deflection of the probe light. The non-invasive material analyzer 1 can be miniaturized.

[0092] At least one temperature sensor (eg, temperature sensors 25 , 26 ) further includes a protective film 28 covering the temperature sensor body 27 .

[0093] The protective film 28 prevents the sample 15 from coming into contact with the temperature sensor body 27. Therefore, the life of the temperature sensor body 27 is extended.

[0094] Implementation method 2.

[0095] Reference Figure 8 Next, a non-invasive substance analyzer 1b according to Embodiment 2 will be described. The non-invasive substance analyzer 1b of this embodiment has the same structure as the non-invasive substance analyzer 1 according to Embodiment 1, but is mainly different in the following points.

[0096] In the non-invasive material analysis device 1 b , the sample support plate 10 includes a low thermal conductive film 14 in addition to the substrate 11 .

[0097] The substrate 11 of this embodiment has a higher thermal conductivity than the substrate 11 of Embodiment 1. In this embodiment, the thermal conductivity of the substrate 11 may be greater than that of the sample 15. In this embodiment, the substrate 11 is formed of a semiconductor substrate such as silicon (thermal conductivity: about 160 W / (m·K)). Since the substrate 11 is formed of a semiconductor material, the through hole 13 having a small size (for example, a diameter of several tens of μm) can be easily formed using a semiconductor microfabrication process.

[0098] The low thermal conductive film 14 is provided on the substrate 11. The low thermal conductive film 14 has a lower thermal conductivity than the substrate 11. The thermal conductivity of the low thermal conductive film 14 is, for example, 20% or less of the thermal conductivity of the substrate 11. The thermal conductivity of the low thermal conductive film 14 may be 10% or less of the thermal conductivity of the substrate 11, 5% or less of the thermal conductivity of the substrate 11, 2% or less of the thermal conductivity of the substrate 11, or 1% or less of the thermal conductivity of the substrate 11. The low thermal conductive film 14 is formed of, for example, silicon dioxide (thermal conductivity: 1.4 W / (m·K)).

[0099] The main surface 10a is formed of a low thermal conductive film 14. A part of the main surface 10a may be formed of the low thermal conductive film 14. The sample mounting area 12 is formed of the low thermal conductive film 14. The temperature sensors 25 and 26 are provided on the low thermal conductive film 14. The through hole 13 is provided in both the substrate 11 and the low thermal conductive film 14.

[0100] Reference Fig. 9 By comparing Example 2 of the present embodiment with Comparative Examples 2-1 and 2-2, the function of the non-invasive material analysis device 1b of the present embodiment is described.

[0101] In Example 2, the substrate 11 is formed of silicon, and the low thermal conductive film 14 is formed of silicon dioxide. In addition, in Example 2, the diameter of the through hole 13 is 36 μm, and the diameter of the light irradiation area 21b of the excitation light 21 is 30 μm. Comparative Example 2-1 is the same as Example 2, but the through hole 13 is not formed in the substrate 11. Comparative Example 2-2 is the same as Comparative Example 2-1, but in Comparative Example 2-2, it is assumed that the transmittance of the substrate 11 with respect to the excitation light 21 is 100%. Fig. 9 The normalized temperature variation amplitude is the temperature variation amplitude of each point on the main surface 10a of Example 2, Comparative Example 2-1, and Comparative Example 2-2, which is normalized by the temperature variation amplitude of the edge of the through hole 13 in the main surface 10a of Example 2. The temperature variation amplitude of each point on the main surface 10a is given by the difference between the temperature of each point on the main surface 10a when the sample 15 is not irradiated with the excitation light 21 and the temperature of each point on the main surface 10a when the sample 15 is irradiated with the excitation light 21.

[0102] In Example 2, a through hole 13 is provided in the sample support plate 10. Therefore, the excitation light 21 is not absorbed by the sample support plate 10, but reaches the sample 15 with a stronger light intensity. The absorption heat of the sample 15 increases. In addition, the thermal conductivity of the air in the through hole 13 (0.024 W / (m·K)) is lower than the thermal conductivity of the substrate 11 (for example, the thermal conductivity of silicon: about 160 W / (m·K)). Therefore, the absorption heat of the sample 15 is difficult to dissipate in the thickness direction of the sample support plate 10 (the direction in which the main surface 10a and the main surface 10b face each other). The temperature variation range of the main surface 10a in the analysis of the sample 15 becomes larger. In Example 2, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0103] In contrast, in Comparative Example 2-1, the through hole 13 is not provided in the sample support plate 10, but the substrate 11 is formed of silicon and can transmit the excitation light 21. Therefore, the excitation light 21 reaches the sample 15, and the temperature variation range of the main surface 10a is not zero. However, in Comparative Example 2-1, a part of the excitation light 21 is reflected by the main surface 10b or absorbed by the substrate 11. Therefore, the intensity of the excitation light 21 reaching the sample 15 in Comparative Example 2-1 is less than the intensity of the excitation light 21 reaching the sample 15 in Example 2. Furthermore, in Comparative Example 2-1, the absorption heat of the sample 15 diffuses faster in the thickness direction of the sample support plate 10 (the direction in which the main surface 10a and the main surface 10b face each other) than in Example 2. As a result, the temperature variation range of the main surface 10a in Comparative Example 2-1 is smaller than the temperature variation range of the main surface 10a in Example 2. In Comparative Example 2-1, it is impossible to accurately analyze the substance in the sample 15 or on the surface of the sample 15.

[0104] In Comparative Example 2-2, the through hole 13 is not provided in the substrate 11. Therefore, in Comparative Example 2-2, the absorbed heat of the sample 15 diffuses rapidly in the thickness direction of the sample support plate 10 (the direction in which the main surface 10a and the main surface 10b face each other) compared with Example 2. The temperature variation range of the main surface 10a in Comparative Example 2-2 is smaller than the temperature variation range of the main surface 10a in Example 2. In Comparative Example 2-2, the substance in the sample 15 or on the surface of the sample 15 cannot be accurately analyzed.

[0105] The non-invasive material analyzer 1 b of the present embodiment has the following effects in addition to the effects of the non-invasive material analyzer 1 of the first embodiment.

[0106] In the non-invasive material analysis device 1b of the present embodiment, the sample support plate 10 includes a substrate 11 and a low thermal conductivity film 14. The low thermal conductivity film 14 is provided on the substrate 11 and has a lower thermal conductivity than the substrate 11. At least a portion of the first main surface (main surface 10a) is formed by the low thermal conductivity film 14. At least one temperature sensor (for example, temperature sensors 25, 26) is provided on the low thermal conductivity film 14.

[0107] Due to the low thermal conductivity film 14, the absorbed heat of the sample 15 is difficult to dissipate in the thickness direction of the sample support plate 10 (the direction in which the main surface 10a and the main surface 10b face each other). When the excitation light 21 is irradiated to the sample 15, the temperature signal output from at least one temperature sensor (for example, the temperature sensors 25 and 26) becomes larger. Therefore, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0108] Implementation method 3.

[0109] Reference Fig.10 as well as Fig.11 A non-invasive substance analyzer 1c according to Embodiment 3 will be described. The non-invasive substance analyzer 1c of this embodiment has the same structure as the non-invasive substance analyzer 1 according to Embodiment 1, but is mainly different in the following points.

[0110] The non-invasive material analyzer 1c further includes reference temperature sensors 40 and 41. The reference temperature sensors 40 and 41 are configured similarly to the temperature sensors 25 and 26. Specifically, the reference temperature sensors 40 and 41 include a temperature sensor body 27 (see Figure 3 The reference temperature sensors 40 and 41 may further include a protective film 28 covering the temperature sensor body 27 (see Figure 3 ).

[0111] The reference temperature sensors 40 and 41 are provided on the main surface 10a. The reference temperature sensors 40 and 41 are provided in the sample mounting area 12 and in contact with the sample 15. The reference temperature sensors 40 and 41 output reference temperature signals corresponding to the temperature of the sample 15 to the lock-in amplifier 34. Specifically, the reference temperature sensor 40 outputs a reference temperature signal corresponding to the temperature of the portion of the sample 15 in contact with the reference temperature sensor 40. The reference temperature sensor 41 outputs a reference temperature signal corresponding to the temperature of the portion of the sample 15 in contact with the reference temperature sensor 41.

[0112] In the case where the sample 15 is a living body, during the analysis of the substance in the sample 15 or on the surface of the sample 15, a thermal change of the sample 15 (e.g., a change in the body temperature of the living body, etc.) or a movement of the sample 15 (e.g., a contraction or relaxation of the muscles contained in the sample 15, or a change in the position of the sample 15, etc.) may sometimes occur. The reference temperature sensors 40 and 41 are not affected by the absorbed heat of the sample 15, but detect the temperature change caused by the thermal change or movement of the sample 15. Therefore, when looking down at the main surface 10a, the distance d2 between each of the reference temperature sensors 40 and 41 and the through hole 13 is greater than the distance d1 between each of the temperature sensors 25 and 26 and the through hole 13. The distance d2 is, for example, more than 10 times the distance d1. The distance d2 may also be more than 20 times the distance d1. In one example, the distance d1 is 5 μm and the distance d2 is 200 μm.

[0113] In a plan view of the main surface 10a, the reference temperature sensors 40 and 41 are arranged rotationally symmetrically with respect to the central axis 13c of the through hole 13. Therefore, the temperature change caused by the thermal change or movement of the sample 15 can be detected more accurately.

[0114] When the main surface 10a is viewed from above, the reference temperature sensor 40 is arranged in the same direction as the temperature sensor 25 with respect to the central axis 13c of the through hole 13. Therefore, the change of the reference temperature signal of the reference temperature sensor 40 caused by the thermal change or movement of the sample 15 during the analysis of the sample 15 is the same as the change of the temperature signal of the temperature sensor 25 caused by the thermal change or movement of the sample 15 during the analysis of the sample 15. The reference temperature sensor 40 is not affected by the absorbed heat of the sample 15, and can more accurately detect the change of the temperature signal of the temperature sensor 25 caused by the thermal change or movement of the sample 15 during the analysis of the sample 15.

[0115] When the main surface 10a is viewed from above, the reference temperature sensor 41 is arranged in the same direction as the temperature sensor 26 with respect to the central axis 13c of the through hole 13. Therefore, the change of the temperature signal of the reference temperature sensor 41 caused by the thermal change or movement of the sample 15 during the analysis of the sample 15 is the same as the change of the temperature signal of the temperature sensor 26 caused by the thermal change or movement of the sample 15 during the analysis of the sample 15. The reference temperature sensor 41 is not affected by the absorbed heat of the sample 15, and can more accurately detect the change of the temperature signal of the temperature sensor 26 caused by the thermal change or movement of the sample 15 during the analysis of the sample 15.

[0116] The lock-in amplifier 34 outputs the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26 to the signal processing unit 37, similarly to the first embodiment. The temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26 are affected by the variation of the temperature signal caused by the thermal variation or movement of the sample 15 during the analysis of the sample 15, in addition to the influence of the absorbed heat of the sample 15. In order to accurately analyze the substance in the sample 15 or on the surface of the sample 15, it is necessary to remove the influence of the variation of the temperature signal caused by the thermal variation or movement of the sample 15 during the analysis of the sample 15 from the temperature variation amplitude signal of the temperature sensor 25 and the temperature variation amplitude signal of the temperature sensor 26.

[0117] Therefore, the signal processing unit 37 receives the reference temperature signal of the reference temperature sensor 40 and the reference temperature signal of the reference temperature sensor 41. The signal processing unit 37 calculates the variation range of the reference temperature signal of the reference temperature sensor 40 in the analysis of the sample 15 as the reference temperature variation range signal of the reference temperature sensor 40. The signal processing unit 37 calculates the variation range of the reference temperature signal of the reference temperature sensor 41 in the analysis of the sample 15 as the reference temperature variation range signal of the reference temperature sensor 41.

[0118] The signal processing unit 37 calculates the difference between the temperature variation amplitude signal of the temperature sensor 25 and the reference temperature variation amplitude signal of the reference temperature sensor 40 as the corrected temperature variation amplitude signal of the temperature sensor 25. The corrected temperature variation amplitude signal of the temperature sensor 25 is the temperature variation amplitude signal of the temperature sensor 25 caused by the absorbed heat of the sample 15, from which the influence of the variation of the temperature signal caused by the thermal variation or movement of the sample 15 in the analysis of the sample 15 is removed. Similarly, the signal processing unit 37 calculates the difference between the temperature variation amplitude signal of the temperature sensor 26 and the reference temperature variation amplitude signal of the reference temperature sensor 41 as the corrected temperature variation amplitude signal of the temperature sensor 26. The corrected temperature variation amplitude signal of the temperature sensor 26 is the temperature variation amplitude signal of the temperature sensor 26 caused by the absorbed heat of the sample 15, from which the influence of the variation of the temperature signal caused by the thermal variation or movement of the sample 15 in the analysis of the sample 15 is removed.

[0119] The signal processing unit 37 calculates the average of the corrected temperature variation amplitude signal of the temperature sensor 25 and the corrected temperature variation amplitude signal of the temperature sensor 26 as an average corrected temperature variation amplitude signal. The substance analysis unit 38 analyzes the substance in the sample 15 or on the surface of the sample 15 based on the average corrected temperature variation amplitude signal.

[0120] (Variation Example)

[0121] The temperature sensor 26 may be omitted, and the number of the temperature sensor 25 may be one. In this case, the signal processing unit 37 outputs the corrected temperature variation amplitude signal of the temperature sensor 25 to the substance analysis unit 38. The substance analysis unit 38 analyzes the substance in the sample 15 or on the surface of the sample 15 based on the corrected temperature variation amplitude signal of the temperature sensor 25.

[0122] The non-invasive material analyzer 1 c of the present embodiment has the following effects in addition to the effects of the non-invasive material analyzer 1 of the first embodiment.

[0123] The non-invasive material analysis device 1c of this embodiment further includes reference temperature sensors 40 and 41 provided on the first main surface (main surface 10a). The reference temperature sensors 40 and 41 are provided in the sample mounting area 12 and are in contact with the sample 15. When the first main surface is viewed from above, the second distance (distance d2) between the reference temperature sensors 40 and 41 and the through hole 13 is 10 times or more the first distance (distance d1) between the temperature sensors 25 and 26 and the through hole 13.

[0124] The reference temperature sensors 40 and 41 detect temperature changes during analysis of the sample 15 without being affected by the absorbed heat of the sample 15. Therefore, the reference temperature sensors 40 and 41 are not affected by changes in the temperature signal caused by thermal changes or movement of the sample 15 during analysis of the sample 15, and can more accurately detect temperature changes caused by the absorbed heat of the sample 15. It is possible to more accurately analyze substances in the sample 15 or on the surface of the sample 15.

[0125] In the non-invasive material analysis device 1c of the present embodiment, the signal processing unit 37 calculates a corrected temperature variation amplitude signal of at least one temperature sensor by correcting the temperature variation amplitude signal of at least one temperature sensor (e.g., the temperature sensors 25 and 26) using the reference temperature variation amplitude signal of the reference temperature sensors 40 and 41. The material analysis unit 38 analyzes a material in the sample 15 or on the surface of the sample 15 based on the corrected temperature variation amplitude signal of the at least one temperature sensor.

[0126] By correcting the temperature variation amplitude signal of at least one temperature sensor (e.g., temperature sensors 25, 26) with the reference temperature variation amplitude signal of reference temperature sensors 40, 41, the temperature variation caused by the absorbed heat of the sample 15 can be detected more accurately without being affected by the variation of the temperature signal caused by the thermal variation or movement of the sample 15 during the analysis of the sample 15. Therefore, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0127] Implementation method 4.

[0128] Reference Fig.12 as well as Fig.13 A non-invasive substance analyzer 1d according to a fourth embodiment will be described. The non-invasive substance analyzer 1d of this embodiment has the same structure as the non-invasive substance analyzer 1 according to the first embodiment, but is mainly different in the following points.

[0129] The non-invasive material analysis device 1d further includes an optical medium 45. The optical medium 45 transmits the excitation light 21. The transmittance of the optical medium 45 to the excitation light 21 is greater than the transmittance of the sample support plate 10 (substrate 11) to the excitation light 21. When the excitation light 21 is mid-infrared light, the optical medium 45 is formed of, for example, chalcogenide glass (SSbSnGe).

[0130] The optical medium 45 plugs the through hole 13. A portion of the sample loading area 12 is formed by the optical medium 45. The entire sample loading area 12 may be formed by the optical medium 45. The sample 15 may be loaded on the optical medium 45. A portion of the through hole 13 is filled with the optical medium 45. A portion of the through hole 13 that is closer to the main surface 10b than the optical medium 45 is a hollow that is not filled with the optical medium 45. The excitation light 21 is irradiated to the sample 15 via the optical medium 45 and the hollow. The entire through hole 13 may be filled with the optical medium 45.

[0131] The thermal conductivity of the optical medium 45 is lower than that of the substrate 11. The thermal conductivity of the optical medium 45 may be 10% or less of the thermal conductivity of the substrate 11, 5% or less of the thermal conductivity of the substrate 11, or 2% or less of the thermal conductivity of the substrate 11. For example, the substrate 11 is made of silicon (thermal conductivity: about 160 W / (m·K)), and the optical medium 45 is made of chalcogenide glass (thermal conductivity: 0.36 W / (m·K)). The thermal conductivity of air in the cavity (0.024 W / (m·K)) is lower than that of the substrate 11.

[0132] The non-invasive substance analyzer 1 d of the present embodiment achieves the following effects similar to those of the non-invasive substance analyzer 1 of the first embodiment.

[0133] The non-invasive material analyzer 1d of this embodiment further includes an optical medium 45 that transmits the excitation light 21. The optical medium 45 blocks the through hole 13. At least a part of the sample placement area 12 is formed by the optical medium 45. The excitation light 21 is irradiated to the sample 15 via the optical medium 45.

[0134] Therefore, the excitation light 21 is not absorbed by the sample support plate 10, but reaches the sample 15 with a stronger light intensity. The absorption heat of the sample 15 increases. In addition, the absorption heat of the sample 15 is difficult to dissipate in the thickness direction of the sample support plate 10 (the direction in which the first main surface (main surface 10a) and the second main surface (main surface 10b) face each other). When the excitation light 21 is irradiated to the sample 15, the temperature signal output from the temperature sensors 25 and 26 becomes larger. The substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0135] The sample 15 can be placed on the optical medium 45. Therefore, even if the size of the sample 15 is smaller than the size of the through hole 13 or even if the sample 15 is liquid, substances in the sample 15 or on the surface of the sample 15 can be analyzed.

[0136] The optical medium 45 transparent to the excitation light 21 such as mid-infrared light is more expensive and has lower mechanical strength than the sample support plate 10 (substrate 11). The optical medium 45 is provided in the through hole 13 of the sample support plate 10 (substrate 11), so the amount of the optical medium 45 used is reduced compared to the case where the entire sample support plate 10 (substrate 11) is formed by the optical medium 45. Therefore, the mechanical strength of the non-invasive material analysis device 1d is improved, and the cost of the non-invasive material analysis device 1d can be reduced.

[0137] In the non-invasive material analysis device 1 d of the present embodiment, the sample support plate 10 includes a substrate 11 . The optical medium 45 has a lower thermal conductivity than the substrate 11 .

[0138] Therefore, the absorbed heat of the sample 15 is difficult to dissipate in the thickness direction of the sample support plate 10 (the direction in which the first main surface (main surface 10a) and the second main surface (main surface 10b) face each other). When the excitation light 21 is irradiated to the sample 15, the temperature signal output from the temperature sensors 25 and 26 becomes larger. Therefore, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0139] Implementation method 5.

[0140] Reference Fig.14 as well as Fig.15 Next, a non-invasive substance analyzer 1e according to Embodiment 5 will be described. The non-invasive substance analyzer 1e of this embodiment has the same structure as the non-invasive substance analyzer 1d of Embodiment 4, but is mainly different in the following points.

[0141] When the main surface 10a is viewed from above, the size of the through hole 13 of the present embodiment is larger than that of the through hole 13 of the fourth embodiment, and the size of the optical medium 45 of the present embodiment is larger than that of the optical medium 45 of the fourth embodiment. For example, when the main surface 10a is viewed from above, the diameter of the through hole 13 of the present embodiment and the diameter of the optical medium 45 are 200 μm, respectively. In the present embodiment, the temperature sensors 25 and 26 are arranged on the optical medium 45. In the present embodiment, as in the fourth embodiment, the thermal conductivity of the optical medium 45 is lower than that of the substrate 11. When the main surface 10a is viewed from above, the temperature sensors 25 and 26 are arranged outside the light irradiation area 21b of the excitation light 21.

[0142] The non-invasive substance analyzer 1e of this embodiment has the following effects in addition to the effects of the non-invasive substance analyzer 1d of the fourth embodiment.

[0143] In the non-invasive material analysis device 1 e of the present embodiment, at least one temperature sensor (for example, the temperature sensors 25 and 26 ) is disposed on the optical medium 45 having a lower thermal conductivity than the substrate 11 .

[0144] Therefore, the absorbed heat of the sample 15 is difficult to dissipate in the thickness direction of the sample support plate 10 (the direction in which the first main surface (main surface 10a) and the second main surface (main surface 10b) face each other), and is also difficult to dissipate in the direction in which the first main surface extends. When the sample 15 is irradiated with the excitation light 21, the temperature signal output from at least one temperature sensor (for example, the temperature sensors 25 and 26) becomes larger. Therefore, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0145] Implementation method 6.

[0146] Reference Fig.16 as well as Fig.17 Next, a non-invasive substance analyzer 1f according to Embodiment 6 will be described. The non-invasive substance analyzer 1f of this embodiment has the same structure as the non-invasive substance analyzer 1 according to Embodiment 1, but is mainly different in the following points.

[0147] In the non-invasive material analysis device 1f, the temperature sensors 25 and 26 (see Figure 1 as well as Figure 2 ) and includes a temperature sensor 50. The temperature sensor 50 includes a first optical waveguide 51, a waveguide type ring resonator 52, a second optical waveguide 53, and a cladding 54. The temperature sensor 50 may further include terminal portions 55 and 56.

[0148] The substrate 11 supports the first optical waveguide 51, the waveguide type ring resonator 52, the second optical waveguide 53, and the cladding 54. The substrate 11 has a main surface 10b. The substrate 11 is, for example, a silicon substrate.

[0149] The probe light emitted from the probe light source 58 enters the first optical waveguide 51. The wavelength of the probe light may be shorter than the wavelength of the excitation light 21. For example, the probe light source 58 is a laser diode for optical communication, and the wavelength of the probe light is 1100 nm to 1700 nm.

[0150] The first optical waveguide 51 includes an end 51a into which the probe light is incident and an end 51b on the opposite side of the end 51a. The first optical waveguide 51 has a higher refractive index than the cladding 54. The probe light propagates in the first optical waveguide 51. The first optical waveguide 51 is, for example, a silicon waveguide.

[0151] The waveguide ring resonator 52 is optically coupled to the first optical waveguide 51. The waveguide ring resonator 52 has a higher refractive index than the cladding 54. The probe light propagates in the waveguide ring resonator 52. The waveguide ring resonator 52 has a thermo-optical effect. The waveguide ring resonator 52 is, for example, a silicon waveguide. The thermo-optical system number of silicon is 2.3×10 -4 (K -1 Silicon has a relatively large number of thermo-optical systems among optical materials used for optical waveguides. The through hole 13 is formed inside the waveguide type ring resonator 52 .

[0152] The second optical waveguide 53 is optically coupled to the waveguide type ring resonator 52. The second optical waveguide 53 has a higher refractive index than the cladding 54. The probe light propagates in the second optical waveguide 53. When the main surface 10a is viewed from above, the second optical waveguide 53 is arranged symmetrically with the first optical waveguide 51 with respect to the waveguide type ring resonator 52. The second optical waveguide 53 includes an end 53a optically coupled to the light intensity detector 59 and an end 53b on the opposite side of the end 53a. The ends 51a and 53a are on the same side relative to the waveguide type ring resonator 52. The ends 51b and 53b are on the same side relative to the waveguide type ring resonator 52.

[0153] The cladding 54 separates the first optical waveguide 51, the waveguide type ring resonator 52, and the second optical waveguide 53 from the substrate 11. The cladding 54 covers the first optical waveguide 51, the waveguide type ring resonator 52, and the second optical waveguide 53. The cladding 54 has a main surface 10a. The thermal conductivity of the cladding 54 is lower than the thermal conductivity of the substrate 11. The cladding 54 is formed of, for example, silica-based glass.

[0154] The terminal portion 55 is provided at the end 51b of the first optical waveguide 51. The terminal portion 56 is provided at the end 53b of the second optical waveguide 53. The terminal portions 55 and 56 scatter or absorb the probe light to reduce the return light of the probe light that advances to the waveguide type ring resonator 52, the probe light source 58, and the light intensity detector 59. The terminal portions 55 and 56 are formed, for example, of a tapered waveguide that is easily scattered outside the waveguide and an electrode (for example, a metal electrode) that absorbs the scattered light.

[0155] Since the excitation light 21 is absorbed by the material in the sample 15 or on the surface of the sample 15, absorption heat is generated in the sample 15. The absorption heat of the sample 15 is conducted in the waveguide type ring resonator 52, and the temperature of the waveguide type ring resonator 52 changes. The waveguide type ring resonator 52 has a thermo-optical effect. Therefore, when the temperature of the waveguide type ring resonator 52 changes, the refractive index of the waveguide type ring resonator 52 changes, and the coupling rate of the probe light from the first optical waveguide 51 to the second optical waveguide 53 via the waveguide type ring resonator 52 changes.

[0156] The light intensity detector 59 is, for example, a photodiode. The light intensity detector 59 detects the light intensity of the probe light from the first optical waveguide 51 to the second optical waveguide 53 via the waveguide type ring resonator 52. The light intensity detector 59 is connected to the lock-in amplifier 34. The light intensity detector 59 outputs a light intensity signal of the probe light to the lock-in amplifier 34.

[0157] The lock-in amplifier 34 performs synchronous detection on the light intensity signal of the detection light received from the light intensity detector 59 using the excitation light intensity signal received from the light detector 24. The lock-in amplifier 34 outputs a DC component proportional to the amplitude of the light intensity signal of the light intensity detector 59. The DC component corresponds to the temperature variation amplitude of the sample 15 during the analysis of the sample 15, and is a temperature variation amplitude signal of the temperature sensor 50. The lock-in amplifier 34 outputs the temperature variation amplitude signal of the temperature sensor 50 to the material analysis unit 38.

[0158] The substance analyzer 38 receives the temperature variation amplitude signal of the temperature sensor 50 from the lock-in amplifier 34. The substance analyzer 38 analyzes the substance in the sample 15 or on the surface of the sample 15 based on the temperature variation amplitude signal of the temperature sensor 50.

[0159] The non-invasive substance analyzer 1f of the present embodiment achieves the following effects similar to those of the non-invasive substance analyzer 1 of the first embodiment.

[0160] In the non-invasive material analysis device 1f of the present embodiment, the temperature sensor 50 includes: a first optical waveguide 51 to which the detection light is incident; a waveguide-type ring resonator 52 optically coupled to the first optical waveguide 51; and a second optical waveguide 53 optically coupled to the waveguide-type ring resonator 52 and a light intensity detector 59 for detecting the intensity of the detection light.

[0161] In the non-invasive material analysis device 1f, the through hole 13 through which the excitation light 21 passes is provided in the sample support plate 10. Therefore, the excitation light 21 is not absorbed by the sample support plate 10, but reaches the sample 15 with a stronger light intensity. The absorption heat of the sample 15 increases. In addition, the absorption heat of the sample 15 is difficult to dissipate in the thickness direction of the sample support plate 10 (the direction in which the first main surface (main surface 10a) and the second main surface (main surface 10b) face each other). When the excitation light 21 is irradiated to the sample 15, the temperature signal output from the temperature sensor 50 becomes larger. Therefore, the substance in the sample 15 or on the surface of the sample 15 can be analyzed more accurately.

[0162] It should be considered that the embodiments 1-6 disclosed in this disclosure are only illustrative in all points and are not limited thereto. As long as there is no contradiction, at least two of the embodiments 1-6 disclosed in this disclosure may be combined. The scope of the present disclosure is not indicated by the above description, but by the claims, and is intended to include all changes within the meaning and scope equivalent to the claims.

Claims

1. A non-invasive material analysis device comprising: A sample support plate having a first main surface including a sample mounting area and a second main surface opposite to the first main surface; an excitation light source radiating excitation light toward a sample placed on the sample placement area; At least one temperature sensor is disposed on the first main surface; as well as A reference temperature sensor is provided on the first main surface. The sample support plate is provided with a through hole extending from the sample mounting area to the second main surface. The excitation light is irradiated to the sample through the through hole, The at least one temperature sensor is disposed in the sample holding area and in contact with the sample, The reference temperature sensor is disposed in the sample placement area and in contact with the sample. When the first main surface is viewed from above, a second distance between the reference temperature sensor and the through hole is at least 10 times the first distance between the at least one temperature sensor and the through hole. Material analysis is performed based on the detection values ​​of the at least one temperature sensor and the reference temperature sensor.

2. The non-invasive material analysis device according to claim 1, wherein: The sample support plate includes a substrate and a low thermal conductivity film, wherein the low thermal conductivity film is disposed on the substrate and has a lower thermal conductivity than the substrate. At least a portion of the first main surface is formed by the low thermal conductive film, The at least one temperature sensor is disposed on the low thermal conductivity film.

3. The non-invasive material analysis device according to claim 1 or 2, wherein: The non-invasive material analysis device further comprises: A periodic intensity modulation mechanism, which periodically modulates the intensity of the excitation light irradiated to the sample to generate a temperature variation amplitude signal of the at least one temperature sensor; and Material Analysis Department, The substance analysis unit analyzes a substance in the sample or on the surface of the sample according to the temperature variation amplitude signal of the at least one temperature sensor. The temperature variation range signal corresponds to a temperature variation range of the sample measured by the at least one temperature sensor during analysis of the sample.

4. The non-invasive material analysis device according to claim 1 or 2, wherein: The non-invasive material analysis device further comprises: a signal processing unit; and Material Analysis Department, The at least one temperature sensor is a plurality of temperature sensors, The signal processing unit outputs an average of a plurality of temperature variation amplitude signals. The plurality of temperature variation amplitude signals respectively correspond to temperature variation amplitudes of the sample measured by corresponding temperature sensors among the plurality of temperature sensors during analysis of the sample, The substance analysis unit analyzes a substance in the sample or on the surface of the sample based on the average of the plurality of temperature variation amplitude signals.

5. The non-invasive material analysis device according to claim 1 or 2, wherein: The non-invasive material analysis device further comprises: a signal processing unit; and Material Analysis Department, The signal processing unit calculates a corrected temperature variation amplitude signal of the at least one temperature sensor by correcting the temperature variation amplitude signal of the at least one temperature sensor using the reference temperature variation amplitude signal of the reference temperature sensor. The substance analysis unit analyzes a substance in the sample or on the surface of the sample based on the corrected temperature variation amplitude signal. The temperature variation amplitude signal corresponds to a temperature variation amplitude of the sample measured by the at least one temperature sensor during analysis of the sample. The reference temperature variation range signal corresponds to a temperature variation range of the sample measured by the reference temperature sensor during analysis of the sample.

6. The non-invasive material analysis device according to claim 1 or 2, wherein: The at least one temperature sensor comprises a temperature sensor body, The temperature sensor body is a thermocouple, a thermopile, a thermistor or a diode.

7. The non-invasive material analysis device according to claim 6, wherein: The at least one temperature sensor further includes a protection film covering the temperature sensor body.

8. The non-invasive material analysis device according to claim 1 or 2, wherein: The at least one temperature sensor includes: a first optical waveguide into which the probe light is incident; a waveguide type ring resonator optically coupled to the first optical waveguide; and a second optical waveguide optically coupled to the waveguide type ring resonator and a light intensity detector that detects the intensity of the probe light.

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