Non-invasive component analysis device

Abstract

The excitation light source (1) emits excitation light that travels through the optical medium (3) toward a sample (5) placed on the sample placement surface. The probe light source (2) emits probe light that travels through the optical medium (3). The light position detector (4) outputs a signal representing the horizontal position and a signal representing the height position of the emitted probe light emitted from the optical medium (3). The differential detector (10) outputs a differential signal between the signal representing the horizontal position and the signal representing the height position. The calculator (11) calculates the amount or concentration of a component to be measured in the sample based on the signal output from the differential detector (10).

Description

[Technical field]

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

[0002] Conventionally, a non-invasive component analyzer and a non-invasive component analyzer for a substance have been known. For example, the method described in JP-A-2017-519214 (Patent Document 1) includes the steps of: arranging an optical medium on the surface of a substance so that at least one region of the surface of the optical medium is in contact with the surface of the substance; irradiating an excitation light beam having an excitation wavelength onto the surface of the substance through the surface region of the optical medium in contact with the surface of the substance; emitting a probe light beam onto a surface region of the optical medium in direct contact with the surface of the substance through the optical medium, the probe light beam and the excitation light beam overlap at the interface between the optical medium and the surface of the substance, and the probe light beam is reflected at the interface; directly or indirectly detecting the deflection of the reflected probe light beam according to the wavelength of the excitation light beam; and analyzing the substance based on the deflection of the reflected probe light beam depending on the wavelength of the excitation light beam. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special publication 2017-519214 Summary of the Invention [Problem to be solved by the invention]

[0004] In the method described in US Pat. No. 5,999,543, a photodiode is used to directly or indirectly detect the deflection of the reflected probe beam.

[0005] There is a problem that the analytical accuracy is reduced due to vibration of the photodiode caused by the outside air and other environmental factors. The deflection of the probe light beam is determined by its positional relationship with the irradiation of the excitation light, but it is not necessarily one-dimensional, either horizontally or vertically, and may change in two dimensions. Since the photodiode detects only the signal component in the corresponding dimensional direction, the signal intensity may be reduced. As a result, the analytical accuracy is reduced.

[0006] Therefore, an object of the present disclosure is to provide a highly accurate non-invasive component analysis device. [Means for solving the problem]

[0007] The noninvasive component analysis device disclosed herein includes an optical medium including a sample mounting surface, an excitation light source that emits excitation light that travels through the optical medium toward a sample placed on the sample mounting surface, a probe light source that emits probe light that travels through the optical medium, a light position detector that outputs a signal representing the horizontal position and a signal representing the height position of the emitted probe light emitted from the optical medium, a differential detector that outputs a differential signal between the signal representing the horizontal position and the signal representing the height position, and a calculator that calculates the amount or concentration of a component to be measured in the sample based on the signal output from the differential detector. Effect of the Invention

[0008] The non-invasive component analysis device disclosed herein is equipped with an optical position detector that outputs a signal representing the horizontal position and a signal representing the height position of the emitted probe light emitted from an optical medium, and a differential detector that outputs a differential signal between the signal representing the horizontal position and the signal representing the height position, thereby enabling highly accurate component analysis. [Brief description of the drawings]

[0009] [Figure 1] 1 is a diagram illustrating a configuration of a non-invasive component analysis device according to a first embodiment. [Diagram 2]13(a) and 13(b) are diagrams showing the optical path of the probe light 7. FIG. [Diagram 3] 1A is a diagram showing an example in which the incident probe light 7 is horizontally incident on the center of the refractive index gradient region 8. FIG. 1B is a diagram showing an example in which the incident probe light 7 is horizontally incident on the refractive index gradient region 8 other than on the center. [Figure 4] 2 is a diagram showing the structure of a light position detector 4. FIG. [Diagram 5] FIG. 13 is a diagram showing the configuration of a non-invasive component analysis device according to a second embodiment. [Figure 6] FIG. 11 is a diagram showing the configuration of a non-invasive component analysis device according to a third embodiment. [Figure 7] FIG. 13 is a diagram showing the configuration of a non-invasive component analysis device according to a fourth embodiment. [Figure 8] FIG. 13 is a diagram showing the configuration of a non-invasive component analysis device according to a fifth embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Embodiment 1 1 is a diagram showing the configuration of a noninvasive component analysis apparatus according to embodiment 1. The noninvasive component analysis apparatus includes an excitation light source 1, a probe light source 2, an optical medium 3, a light position detector 4, a differential detector 10, and a calculator 11.

[0011] The excitation light source 1 includes at least one infrared light source. The excitation light source 1 includes a broadband quantum cascade laser that emits infrared light in all wavelength ranges including the excitation wavelength (wavelength of the fingerprint spectrum) of the component to be measured in the sample 5, or in a part of the wavelength range. When the component to be measured is sugar in the human body, the wavelengths used for measurement are, for example, λ1, λ2, and λ3. The light with wavelengths λ1 and λ2 are excitation wavelengths of sugar in the human body and are absorbed by sugar in the human body. The light with wavelength λ3 is not absorbed by sugar in the human body and is used as a reference wavelength. Four or more wavelengths may be used for measurement.

[0012] Infrared light emitted from the excitation light source 1 passes through the optical medium 3 as excitation light 6 and enters the sample 5. For example, when measuring components contained in a living organism, the excitation light 6 is made to enter through the skin of the finger, arm, ear, etc. of the living organism, and the absorption of light by substances contained inside the living organism, for example the absorption of substances contained in interstitial fluid, is measured.

[0013] The probe light source 2 emits a probe light 7. The probe light 7 enters the optical medium 3 from a third surface 33 of the optical medium 3. The probe light 7 is refracted at the third surface 33 and travels through the optical medium 3 toward the interface between the optical medium 3 (second surface 32) and the sample 5.

[0014] 2(a) and (b) are diagrams showing the optical path of the probe light 7. FIG. In a planar view of the sample placement surface (second surface 32), the optical path of the probe light 7 in the optical medium 3 overlaps partially (Figure 2(a)) or entirely (Figure 2(b)) with the portion of the sample placement surface (second surface 32) that is irradiated by the excitation light 6.

[0015] The probe light 7 is totally internally reflected at the interface between the optical medium 3 (second surface 32) and the sample 5. While the probe light 7 travels through the optical medium 3, the probe light 7 travels through a refractive index gradient region 8 that is generated in the optical medium 3 by heat absorbed by the sample 5. The probe light 7 is refracted in the refractive index gradient region 8, and the traveling direction of the probe light 7 is changed. The probe light 7 is emitted from a fourth surface 34 of the optical medium 3.

[0016] The wavelength of the light output from the probe light source 2 may be in any wavelength band that is transparent to the optical medium 3. For example, a wavelength band such as the visible light region of 400 to 900 nm, which is mass-produced for many purposes and is inexpensive, or the invisible region of 1300 to 1700 nm, which is used in optical fiber communication, may be used.

[0017] The optical medium 3 is made of a material through which the excitation light 6 emitted from the excitation light source 1 and the incident probe light 7 emitted from the probe light source 2 are transmitted. For example, the optical medium 3 is made of a material such as zinc sulfide (ZnS) or zinc selenide (ZnSe), which generally has high transmittance in the wavelength range from visible light to infrared light. When the measurement target is a living body measurement, zinc sulfide (ZnS) can be used as the optical medium 3 in consideration of biological stability. Chalcogenide glass, which has a lower thermal conductivity than zinc sulfide (ZnS) or zinc selenide (ZnSe), may be used so that the change in the refractive index of the optical medium 3 due to heat generated in the sample 5 is localized.

[0018] A case where the optical output of the excitation light source 1 is zero (reference state) will be described. In the reference state, since the state inside the optical medium 3 is uniform, the light output from the probe light source 2 is refracted only when it enters and exits the optical medium 3. In the reference state, the position where the emitted probe light 7a enters the light position detector 4 is set as the reference position RP. In this embodiment, the path of the probe light 7a is shown as a path that is totally reflected once at the interface between the optical medium 3 and the sample 5, but it is sufficient that the path passes through the refractive index gradient region 8 generated in the optical medium 3, and it may be a path that is totally reflected two or more times within the optical medium, or a path that passes near the contact surface with the sample 5 parallel to the contact surface.

[0019] Next, a case where there is output from the excitation light source 1 will be described. The excitation light source 1 outputs infrared light of the fingerprint spectrum wavelength of the component to be measured in the sample 5 as excitation light 6. The excitation light 6 is incident on the sample 5 via the optical medium 3. The excitation light 6 is absorbed by the sample 5. Absorption heat is generated in the sample 5 due to the absorption. The generated absorption heat propagates to the optical medium 3, and a temperature gradient occurs inside the optical medium 3. Since the refractive index of the optical medium generally has temperature dependence, a refractive index gradient region 8 is formed in response to the temperature gradient. This state is called a changed state.

[0020] In the changing state, the incident probe light 7 output from the probe light source 2 passes through the refractive index gradient region 8. The incident probe light 7 is refracted according to the gradient of the refractive index at the position in the refractive index gradient region 8 where it passes. The refracted incident probe light 7 is output from the optical medium 3 as output probe light 7b and enters the light position detector 4. In the changing state, the position where the output probe light 7b enters the light position detector 4 is referred to as a changing position CP. Although FIG. 1 shows the incident position only in the height direction, the incident position also displaces in the horizontal direction.

[0021] If there is a large amount of the component to be measured in sample 5 (i.e., a component with a high absorption coefficient at a certain wavelength of light emitted from excitation light source 1), the amount of light absorbed in sample 5 increases, and therefore the amount of heat generated increases. As a result, the refractive index gradient increases. The relationship between the difference between the reference position RP where the emitted probe light 7a is incident on the light position detector 4 in the reference state and the change position CP where the emitted probe light 7b is incident on the light position detector 4 in the change state and the amount of the component to be measured in sample 5 is approximately close to proportional.

[0022] Fig. 3(a) is a diagram showing an example in which the incident probe light 7 is horizontally incident on the refractive index gradient region 8 at the center. The axis of the incident probe light 7 does not displace in the horizontal direction. Fig. 3(b) is a diagram showing an example in which the incident probe light 7 is horizontally incident on the refractive index gradient region 8 other than at the center. The axis of the incident probe light is deflected in the direction of the higher refractive index.

[0023] The optical position detector 4 can detect the position in two dimensions, that is, the horizontal direction and the height direction. FIG. 4 is a diagram showing the structure of the light position detector 4. As shown in FIG.

[0024] The light position detector 4 has four regions R1 to R4 obtained by dividing a circular or square light receiving element. The light outputs of the regions R1, R2, R3, and R4 are designated as A1, A2, A3, and A4.

[0025] The light position detector 4 outputs to the differential detector 10 a horizontal (X-direction) position signal HO shown in equation (1) and a height (Y-direction) position signal VO shown in equation (2).

[0026] HO = (A1 + A4) - (A2 + A3) ... (1) VO = (A1 + A2) - (A3 + A4) ... (2) The differential detector 10 outputs to a calculator 11 a differential signal DF between the height direction position signal VO and the horizontal direction position signal HO.

[0027] The calculator 11 measures the amount or concentration of the component to be measured in the sample 5 based on the difference between a differential signal DF(1) based on a reference position RP at which the emitted probe light 7a is incident, detected by the light position detector 4, in a reference state in which the excitation light source 1 is not emitting excitation light, and a differential signal DF(2) based on a change position CP at which the emitted probe light 7b is incident, detected by the light position detector 4, in a change state in which the excitation light source 1 is emitting excitation light.

[0028] In the first embodiment, it is possible to remove noise components caused by vibrations and the like that occur commonly in the horizontal and vertical directions by using the light position detector 4 capable of outputting the horizontal and vertical positions of the emitted probe beams 7a and 7b, and the differential detector 10 that outputs a differential signal of the output of the light position detector 4. Furthermore, by detecting all two-dimensional components of the signal generated by the change in the traveling direction of the probe beam, it is possible to reduce the influence of vibrations of the light position detector 4 and increase the signal components, thereby realizing a highly accurate non-invasive component analysis device.

[0029] Embodiment 2 5 is a diagram showing the configuration of a non-invasive component analysis device of embodiment 2. The non-invasive component analysis device of embodiment 2 differs from the non-invasive component analysis device of embodiment 1 in that the non-invasive component analysis device of embodiment 2 includes an optical chopper 20 between the excitation light source 1 and the optical medium 3, and includes a lock-in amplifier 21 between the differential detector 10 and the calculator 11.

[0030] The optical chopper 20 is disposed in the optical path of the excitation light 6. The optical chopper 20 chops the excitation light 6 (continuous light) emitted from the excitation light source 1 at an arbitrary frequency. The excitation light 6 becomes intermittent light (pulsed light) that is turned on and off at a period corresponding to the chopping frequency (frequency at which light is turned on and off) of the optical chopper 20, and is incident on the optical medium 3. A well-known configuration can be applied to the optical chopper 20. The optical chopper 20 has, for example, a rotating disk in which openings that allow the excitation light 6 to pass and light-shielding parts that block the excitation light 6 are arranged in the circumferential direction, and a motor that rotates the rotating disk. By periodically rotating the rotating disk with the motor, it is possible to switch whether or not the excitation light 6 is irradiated on the sample 5. That is, the excitation light 6 is intensity-modulated at the chopping frequency of the optical chopper 20. The chopping frequency of the excitation light 6 is determined by the rotation speed of the rotating disk.

[0031] The optical chopper 20 and the lock-in amplifier 21 are connected to an oscillator (not shown). The oscillator sets the chopping frequency (modulation frequency) of the optical chopper 20. The oscillator generates a control signal for chopping control of the pump light 6, and provides the generated control signal to the optical chopper 20 and the lock-in amplifier 21. The control signal includes the chopping frequency of the optical chopper 20.

[0032] The lock-in amplifier 21 selectively amplifies a signal that is synchronized with the chopping frequency (modulation frequency) of the optical chopper 20, among the signals related to the position of the probe light 7 output from the optical position detector 4. The on-period of the chopping cycle corresponds to the period during which the excitation light 6 is irradiated. The off-period of the chopping cycle corresponds to the period during which the excitation light 6 is not irradiated.

[0033] Embodiment 3 6 is a diagram showing the configuration of a noninvasive component analysis device according to embodiment 3. The noninvasive component analysis device according to embodiment 3 differs from the noninvasive component analysis device according to embodiment 2 in that the noninvasive component analysis device according to embodiment 3 includes filters 30a and 30b between the optical position detector 4 and the differential detector 10.

[0034] Filter 30a selectively transmits a specific frequency band of the height direction position signal VO of the light position detector 4. Filter 30b selectively transmits a specific frequency band of the horizontal direction position signal HO of the light position detector 4. Filters 30a and 30b can filter out, for example, a frequency band that contains many vibration components other than the frequency band corresponding to the ON-OFF frequency of the excitation light 6 emitted from the excitation light source 1.

[0035] By providing filters 30a and 30b after the height direction position signal VO and horizontal direction position signal HO output from the optical position detector 4, noise components outside the frequency band related to the signal components can be removed, thereby enabling higher accuracy.

[0036] Embodiment 4 7 is a diagram showing the configuration of a noninvasive component analysis device according to embodiment 4. The noninvasive component analysis device according to embodiment 4 differs from the noninvasive component analysis device according to embodiment 2 in that the noninvasive component analysis device according to embodiment 4 includes gain adjusters 40a and 40b between the optical position detector 4 and the differential detector 10.

[0037] Gain adjuster 40a adjusts the output gain of height-direction position signal VO of light position detector 4. Gain adjuster 40b adjusts the output gain of horizontal-direction position signal HO of light position detector 4. For example, when the amplitude of the noise component of height-direction position signal VO of light position detector 4 differs from the amplitude of the noise component of horizontal-direction position signal HO, gain adjuster 40a and gain adjuster 40b can adjust the amplitude so that the noise component can be removed when differential detection is performed.

[0038] Embodiment 5. 8 is a diagram showing the configuration of a noninvasive component analysis device according to embodiment 5. The noninvasive component analysis device according to embodiment 5 differs from the noninvasive component analysis device according to embodiment 2 in that the noninvasive component analysis device according to embodiment 5 includes a light position detector 4A instead of the light position detector 4, and further includes a laser control unit 50.

[0039] The light position detector 4A detects the intensities of the received emitted probe beams 7a and 7b. Specifically, the light position detector 4A outputs a sum AO of the light outputs A1, A2, A3, and A4 of the regions R1, R2, R3, and R4.

[0040] AO = A1 + A2 + A3 + A4 … (3) The laser control unit 50 controls the output of the probe light source 2 based on the value of the sum AO. This makes it possible to always keep the intensity of the output incident on the light position detector 4A constant, for example. This allows the non-invasive component analysis device to have even higher accuracy.

[0041] The above embodiments can be combined in any manner. The embodiments disclosed herein should be considered to be illustrative and not restrictive in all respects. 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. [Explanation of symbols]

[0042] 1 excitation light source, 2 probe light source, 3 optical medium, 4, 4A optical position detector, 5 sample, 6 excitation light, 7, 7a, 7b probe light, 8 refractive index gradient region, 10 differential detector, 11 calculator, 20 optical chopper, 21 lock-in amplifier, 30a, 30b filters, 40a, 40b gain adjusters, 50 laser control unit.

Claims

1. an optical medium including a sample placement surface; an excitation light source that emits excitation light that travels through the optical medium toward a sample placed on the sample placement surface; a probe light source that emits a probe light that travels through the optical medium; a light position detector that outputs a signal representing a horizontal position and a signal representing a height position of the emitted probe light emitted from the optical medium; a differential detector that outputs a differential signal between the signal representing the horizontal position and the signal representing the height position; A computing unit that calculates the amount or concentration of a component to be measured in the sample based on the signal output from the differential detector.

2. The non-invasive component analysis device according to claim 1 , wherein, in a plan view of the sample placement surface, an optical path of the probe light in the optical medium overlaps with a portion of the sample placement surface that is irradiated by the excitation light.

3. an optical chopper disposed between the excitation light source and the optical medium; 2. The non-invasive component analysis device according to claim 1, further comprising a lock-in amplifier disposed between said differential detector and said computing unit, said lock-in amplifier selectively amplifying a signal synchronized with a chopping frequency of said optical chopper.

4. a first filter disposed between the optical position detector and the differential detector, the first filter selectively transmitting a specific frequency band of a signal representing the horizontal position; The non-invasive component analysis device according to claim 1 , further comprising: a second filter disposed between the optical position detector and the differential detector, the second filter selectively transmitting a specific frequency band of a signal representing the position in the height direction.

5. a first gain adjuster arranged between the optical position detector and the differential detector, the first gain adjuster being capable of adjusting a gain of a signal representing the horizontal position; The non-invasive component analysis device according to claim 1 , further comprising: a second gain adjuster arranged between the optical position detector and the differential detector, capable of adjusting a gain of a signal representing the position in the height direction.

6. the light position detector outputs the intensity of the emitted probe light; The non-invasive component analysis device according to any one of claims 1 to 5, further comprising a laser control unit that controls an output of the probe light source based on an intensity of the emitted probe light.

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