DEVICE FOR NON-INVASIVE COMPONENT ANALYSIS

Abstract

An excitation light source (1) emits excitation light that propagates through an optical medium (3) towards a sample (5) placed on a sample placement surface. A probe light source (2) emits probe light that propagates through the optical medium (3). A light position detector (4) outputs a signal indicating the position in a horizontal direction and a position in a vertical direction of emission probe light emitted by the optical medium (3). A differential detector (10) outputs a difference signal between the signal indicating the position in the horizontal direction and the signal indicating the position in the vertical direction. A computation unit (11) calculates a quantity or concentration of a component to be measured in the sample based on the signal output by the differential detector (10).

Description

TECHNICAL AREA

[0001] The present disclosure relates to a device for non-invasive component analysis. GENERAL STATE OF THE ART

[0002] Conventionally, devices for non-invasive component analysis and devices for non-invasive component analysis of a substance are known. For example, a method described in Japanese National Patent Publication No. 2017-519214 (PTL 1) comprises: arranging an optical medium on a surface of a substance to bring at least one region of a surface of the optical medium into contact with the surface of the substance;Irradiating the surface of the substance with an excitation luminous flux of an excitation wavelength through the region of the surface of the optical medium that is in contact with the surface of the substance; emitting a probe luminous flux through the optical medium onto the region of the surface of the optical medium that is in direct contact with the surface of the substance, such that the probe luminous flux overlaps the excitation luminous flux at an interface between the optical medium and the surface of the substance and the probe luminous flux is reflected at the interface; directly or indirectly detecting a deflection of the reflected probe luminous flux according to the wavelength of the excitation luminous flux; and analyzing the substance based on the deflection of the reflected probe luminous flux as a function of the wavelength of the excitation luminous flux. LIST OF CITED PUBLICATION LITERATURE

[0003] PTL 1: Japanese National Patent Publication No. 2017-519214 BRIEF DESCRIPTION OF THE INVENTIONAL PROBLEM

[0004] The method described in PTL 1 uses a photodiode for direct or indirect detection of the deflection of the reflected probe luminous flux.

[0005] The problem is that the analysis accuracy is reduced due to vibrations of the photodiode caused by the environment, such as the ambient air. While the deflection of the probe's luminous flux is determined by its position relative to the incident excitation light, it does not necessarily occur in a one-dimensional direction (i.e., either horizontally or vertically) and can vary in two dimensions. Since the photodiode only detects a signal component in one dimension, the signal intensity can decrease, thus reducing the analysis accuracy.

[0006] Accordingly, one objective of the present disclosure is to provide a high-precision device for non-invasive component analysis. SOLUTION TO THE TASK

[0007] According to the present disclosure, a device for non-invasive component analysis comprises: an optical medium with a sample placement area; an excitation light source for emitting excitation light that propagates through the optical medium in the direction of a sample placed on the sample placement area; a probe light source for emitting probe light that propagates through the optical medium; a light position detector for outputting a signal indicating a position in a horizontal direction and a position in a vertical direction of emission probe light emitted by the optical medium; a difference detector for outputting a difference signal between the signal indicating the position in the horizontal direction and the signal indicating the position in the vertical direction;and a calculation unit for calculating a quantity or concentration of a component to be measured in the sample based on the signal output by the differential detector. ADVANTAGEOUS EFFECTS OF THE INVENTION

[0008] Since the device for non-invasive component analysis according to the present disclosure comprises the light position detector for outputting the signal indicating the position in the horizontal direction and the position in the vertical direction of the emission probe light emitted by the optical medium, and the difference detector for outputting the difference signal between the signal indicating the position in the horizontal direction and the signal indicating the position in the vertical direction, the device for non-invasive component analysis can perform a highly accurate component analysis. BRIEF DESCRIPTION OF THE DRAWINGS Fig. Figure 1 is a representation illustrating a configuration of a device for non-invasive component analysis according to a first embodiment. Fig. 2(a) and Fig. 2(b) are representations that each illustrate an optical path of a probe light 7. Fig. Figure 3(a) is a representation showing an example where incident probe light 7 is incident on a refractive index gradient region 8 in the middle in a horizontal direction. Fig. 3(b) is a representation showing an example where the incident probe light 7 falls on the refractive index gradient region 8 at a position other than the center in the horizontal direction. Fig. Figure 4 is a representation illustrating the structure of a light position detector 4. Fig. Figure 5 is a representation illustrating a configuration of a device for non-invasive component analysis in a second embodiment. Fig. Figure 6 is a representation illustrating a configuration of a device for non-invasive component analysis in a third embodiment. Fig. Figure 7 is a representation illustrating a configuration of a device for non-invasive component analysis in a fourth embodiment. Fig. Figure 8 is a representation illustrating a configuration of a device for non-invasive component analysis in a fifth embodiment. DESCRIPTION OF THE EXECUTION FORMS First embodiment.

[0009] Fig. Figure 1 is a representation illustrating a configuration of a device for non-invasive component analysis in a first embodiment. The device for non-invasive component analysis comprises 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 processing unit 11.

[0010] The excitation light source 1 comprises at least one or more infrared light sources. The excitation light source 1 includes a broadband quantum cascade laser that emits infrared light in all or some wavelength ranges, including an excitation wavelength (a wavelength of a fingerprint spectrum) of a component to be measured in a sample 5. If the component to be measured is sugar in a human body, it is assumed that, for example, wavelengths λ1, λ2, and λ3 are used for the measurement. Light with wavelength λ1 and light with wavelength λ2 are excitation wavelengths of the sugar in the human body and are absorbed by the sugar in the human body. Light with wavelength λ3 is not absorbed by the sugar in the human body and is used as a reference wavelength. Four or more wavelengths can be used for the measurement.

[0011] The infrared light emitted by the excitation light source 1 is transmitted as excitation light 6 through the optical medium 3 and strikes the sample 5. For example, when measuring a component contained in a living body, excitation light 6 is emitted from the skin of a finger, arm, ear, or the like of the living body to measure the absorption of the light by a component contained in the living body, such as an absorption by a substance contained in an interstitial fluid.

[0012] The probe light source 2 emits probe light 7. The probe light 7 is incident on the optical medium 3 from a third surface 33. The probe light 7 is refracted at the third surface 33 and propagates through the optical medium 3 towards an interface between the optical medium 3 (a second surface 32) and the sample 5.

[0013] Fig. 2(a) and Fig. 2(b) are representations that each illustrate an optical path of a probe light 7.

[0014] In a top view of a sample placement surface (second surface 32), the optical path of the probe light 7 in the optical medium 3 partially overlaps a section of the sample placement surface (second surface 32) irradiated with excitation light 6 ( Fig. 2(a)) or completely ( Fig. 2(b)).

[0015] The probe light 7 is completely internally reflected at the interface between the optical medium 3 (second surface 32) and the sample 5. As the probe light 7 propagates through the optical medium 3, it passes through a refractive index gradient region 8, which is generated in the optical medium 3 by absorption heat from the sample 5. The probe light 7 is refracted in the refractive index gradient region 8, and one of the propagation directions of the probe light 7 changes. The probe light 7 is emitted from a fourth surface 34 of the optical medium 3.

[0016] The light emitted by the probe light source 2 can have a wavelength in any wavelength band, as long as the light is transmitted through the optical medium 3. For example, it is possible to use a wavelength band such as a range of visible light from 400 to 900 nm, which is mass-produced and inexpensive for many applications, or an invisible range with a wavelength band of 1300 to 1700 nm, which is used for fiber optic communication.

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

[0018] A case is now described in which the light output of the excitation light source 1 is zero (a reference state). Since the state within the optical medium 3 is uniform in the reference state, the light emitted by the probe light source 2 is only refracted when it strikes the optical medium 3 and is emitted by the optical medium 3. A position at which the emission probe light 7a strikes the light position detector 4 in the reference state is defined as the reference position RP.Although in the present embodiment a path on which the probe light 7a is completely reflected once at the interface between the optical medium 3 and the sample 5 is shown as a path of the probe light 7a, the path can be any path that passes through the refractive index gradient region 8 generated in the optical medium 3, and can be a path on which the probe light 7a is completely reflected twice or more in the optical medium, or a path that passes through the vicinity of a contact surface between the optical medium 3 and the sample 5 parallel to the contact surface.

[0019] Next, a case is described in which emission occurs from the excitation light source 1. The excitation light source 1 emits infrared light with the wavelength of the fingerprint spectrum of the component to be measured in the sample 5 as excitation light 6. The excitation light 6 is incident on the sample 5 through the optical medium 3. The excitation light 6 is absorbed by the sample 5. Absorption-related heat is generated in the sample 5. The generated absorption heat propagates in the optical medium 3, and a temperature gradient is created in the optical medium 3. Since the refractive index of the optical medium is generally temperature-dependent, the refractive index gradient range 8 is formed according to the temperature gradient. This state is defined as a modified state.

[0020] In the altered state, the incident probe light 7, emitted by the probe light source 2, passes through the refractive index gradient region 8. At a position where it passes through the refractive index gradient region 8, the incident probe light 7 is refracted according to a gradient of the refractive index. The refracted incident probe light 7 is emitted by the optical medium 3 as emission probe light 7b and strikes the light position detector 4. A position at which the emission probe light 7b, in its altered state, strikes the light position detector 4 is defined as the altered position CP. Fig. 1. If the incidence positions are only shown in one vertical direction, the incidence positions are also shifted in one horizontal direction.

[0021] If the component to be measured is present in large quantities in sample 5 (i.e., a component with a high absorption coefficient at a specific wavelength of the light emitted by the excitation light source 1), the light absorption in sample 5 increases, and consequently, so does the amount of heat generated. As a result, the refractive index gradient increases. The relationship between the quantity of the component to be measured in sample 5 and the difference between the reference position RP, where the emission probe light 7a strikes the light position detector 4 in the reference state, and the modified position CP, where the emission probe light 7b strikes the light position detector 4 in the modified state, is essentially proportional.

[0022] Fig. Figure 3(a) is a representation showing an example where incident probe light 7 falls on the refractive index gradient region 8 in the center in the horizontal direction. One axis of the incident probe light 7 is not shifted in the horizontal direction. Fig. Figure 3(b) is a representation showing an example where the incident probe light 7 strikes the refractive index gradient region 8 at a position other than the center in the horizontal direction. The axis of the incident probe light is deflected in a direction where the refractive index is higher.

[0023] The light position detector 4 can detect a position in a two-dimensional direction including the horizontal direction and the vertical direction.

[0024] Fig. Figure 4 is a representation illustrating the setup of the light position detector 4.

[0025] The light position detector 4 has regions R1 to R4, which are obtained by dividing a circular or square light receiving element into quarters. Light outputs from regions R1, R2, R3, and R4 are defined as A1, A2, A3, and A4, respectively.

[0026] The light position detector 4 outputs a position signal HO in the horizontal direction (an X-direction), represented by expression (1), and a position signal VO in the vertical direction (a Y-direction), represented by expression (2), to the differential detector 10. HO=(A1+A4)−(A2+A3) VO=(A1+A2)−(A3+A4)

[0027] The differential detector 10 outputs a differential signal DF between the position signal VO in the vertical direction and the position signal HO in the horizontal direction to the calculation unit 11.

[0028] The calculation unit 11 measures the quantity or concentration of the component to be measured in the sample 5 based on a difference between a difference signal DF(1) based on the reference position RP, where the emission probe light 7a occurs in the reference state and is detected by the light position detector 4, where the excitation light source 1 does not emit the excitation light, and a difference signal DF(2) based on the changed position CP, where the emission probe light 7b occurs in the changed state and is detected by the light position detector 4, where the excitation light source 1 emits the excitation light.

[0029] In the first embodiment, by using the light position detector 4, which is capable of outputting the horizontal and vertical positions of the emission probe lights 7a and 7b, and the differential detector 10, which outputs the difference signals between the outputs of the light position detector 4, it is possible to eliminate a noise component due to vibrations or the like generated in the horizontal and vertical directions. Furthermore, by detecting all two-dimensional components of a signal generated by a change in the propagation direction of the probe light, it is possible to reduce the influence of vibrations of the light position detector 4 and increase the signal components, thereby enabling the implementation of a high-precision device for non-invasive component analysis. Second embodiment.

[0030] Fig. Figure 5 is a representation illustrating a configuration of a device for non-invasive component analysis in a second embodiment. The device for non-invasive component analysis in the second embodiment differs from the device for non-invasive component analysis in the first embodiment in that the device for non-invasive component analysis in the second embodiment comprises an optical chopper 20 between the excitation light source 1 and the optical medium 3 and a lock-in amplifier 21 between the differential detector 10 and the processing unit 11.

[0031] The optical chopper 20 is arranged in an optical path of the excitation light 6. The optical chopper 20 chops the excitation light 6 (continuous light) emitted by the excitation light source 1 at an arbitrary frequency. The excitation light 6 becomes intermittent light (pulsed light) that is switched on and off in a cycle corresponding to a chopping frequency of the optical chopper 20 (a frequency at which the light is switched on and off) and strikes the optical medium 3. A known configuration can be used for the optical chopper 20. For example, the optical chopper 20 has a rotating disk in which an open section, allowing the passage of excitation light 6, and a light-blocking section, blocking the excitation light 6, are arranged circumferentially, as well as a motor that rotates the disk.Whether or not sample 5 is irradiated with the excitation light 6 can be switched by cyclically rotating the disk with the motor. This means that the intensity of the excitation light 6 is modulated by the chopping frequency of the optical chopper 20. The chopping frequency of the excitation light 6 is determined by the rotational speed of the disk.

[0032] The optical chopper 20 and the lock-in amplifier 21 are connected to an oscillator (not shown). The oscillator sets the chopping frequency (a modulation frequency) of the optical chopper 20. The oscillator generates a control signal for the chopper control of the excitation light 6 and supplies 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.

[0033] The lock-in amplifier 21 selectively amplifies a signal synchronized with the chopping frequency (modulation frequency) of the optical chopper 20, among signals related to the position of the probe light 7 output by the light position detector 4. An ON period of a chopping cycle corresponds to a period in which excitation light 6 is emitted. An OFF period of the chopping cycle corresponds to a period in which no excitation light 6 is emitted. Third embodiment.

[0034] Fig. Figure 6 is a representation illustrating a configuration of a device for non-invasive component analysis in a third embodiment. The device for non-invasive component analysis in the third embodiment differs from the device for non-invasive component analysis in the second embodiment in that the device for non-invasive component analysis in the third embodiment comprises a filter 30a and a filter 30b between the light position detector 4 and the differential detector 10.

[0035] Filter 30a selectively allows a specific frequency band of the position signal VO in the vertical direction of the light position detector 4 to pass through. Filter 30b selectively allows a specific frequency band of the position signal HO in the horizontal direction of the light position detector 4 to pass through. Filter 30a and filter 30b can, for example, remove a frequency band containing a large amount of vibration components that do not correspond to a frequency band that matches an ON-OFF frequency of the excitation light 6 emitted by the excitation light source 1.

[0036] By providing the filter 30a and the filter 30b in a stage that is connected downstream of the position signal VO in the vertical direction and the position signal HO in the horizontal direction, which are output by the light position detector 4, it is possible to eliminate a noise component in a different frequency band than a frequency band that is related to a signal component, thereby achieving higher accuracy. Fourth embodiment.

[0037] Fig. Figure 7 is a representation illustrating a configuration of a device for non-invasive component analysis in a fourth embodiment. The device for non-invasive component analysis in the fourth embodiment differs from the device for non-invasive component analysis in the second embodiment in that the device for non-invasive component analysis in the fourth embodiment comprises a gain controller 40a and a gain controller 40b between the light position detector 4 and the differential detector 10.

[0038] The gain control 40a adjusts the output gain of the position signal VO in the vertical direction of the light position detector 4. The gain control 40b adjusts the output gain of the position signal HO in the horizontal direction of the light position detector 4. For example, if the amplitude of a noise component of the position signal VO in the vertical direction of the light position detector 4 differs from the amplitude of a noise component of the position signal HO in the horizontal direction of the light position detector 4, the amplitudes can be adjusted by the gain control 40a and the gain control 40b so that the noise components can be eliminated when differential detection is performed. Fifth embodiment.

[0039] Fig.Figure 8 is a representation illustrating a configuration of a device for non-invasive component analysis in a fifth embodiment. The device for non-invasive component analysis in the fifth embodiment differs from the device for non-invasive component analysis in the second embodiment in that the device for non-invasive component analysis in the fifth embodiment comprises a light position detector 4A instead of the light position detector 4 and further comprises a laser control unit 50.

[0040] The light position detector 4A detects the intensities of the received emission probe lights 7a and 7b. Specifically, the light position detector 4A outputs a total AO of the optical emissions A1, A2, A3 and A4 of the areas R1, R2, R3 and R4. AO=A1+A2+A3+A4

[0041] The laser control unit 50 controls the output of the probe light source 2 based on a value of the total AO. This ensures, for example, that the intensity of the output incident on the light position detector 4A remains constant. This makes it possible to further improve the accuracy of the device for non-invasive component analysis.

[0042] It should be noted that the embodiments described above can be combined in any way.

[0043] It is understood that the embodiments disclosed herein are in every respect exemplary and not limiting. The scope of this disclosure is defined by the scope of protection of the claims and not by the foregoing description, and is intended to include all modifications within the scope and meaning that correspond to the scope of protection of the claims. REFERENCE MARK LIST

[0044] 1: Excitation light source; 2: Probe light source; 3: Optical medium; 4, 4A: Light position detector; 5: Sample; 6: Excitation light; 7, 7a, 7b: Probe light; 8: Refractive index gradient section; 10: Difference detector; 11: Computing unit; 20: Optical chopper; 21: Lock-in amplifier; 30a, 30b: Filters; 40a, 40b: Gain controller; 50: Laser control unit. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] JP 2017-519214 [0002, 0003]

Claims

[1] Device for non-invasive component analysis, comprising: an optical medium with a sample placement area; an excitation light source for emitting excitation light that propagates through the optical medium towards a sample placed on the sample placement surface; a probe light source for emitting probe light that propagates through the optical medium; a light position detector for outputting a signal indicating a position in a horizontal direction and a position in a vertical direction of emission probe light emitted by the optical medium; a differential detector for outputting a difference signal between the signal indicating the position in the horizontal direction and the signal indicating the position in the vertical direction; and A calculation unit for calculating the quantity or concentration of a component to be measured in the sample based on the signal output by the differential detector. [2] Device for non-invasive component analysis according to claim 1, wherein, in a top view of the sample placement surface, an optical path of the probe light in the optical medium overlaps a section of the sample placement surface irradiated with the excitation light. [3] Device for non-invasive component analysis according to claim 1 or 2, further comprising: an optical chopper arranged between the excitation light source and the optical medium; and a lock-in amplifier positioned between the differential detector and the computation unit to selectively amplify a signal synchronized with a chopping frequency of the optical chopper. [4] Device for non-invasive component analysis according to any one of claims 1 to 3, further comprising: a first filter arranged between the light position detector and the differential detector to selectively allow a specific frequency band of the signal indicating the position in the horizontal direction to pass through; and a second filter, which is arranged between the light position detector and the difference detector, to selectively allow a specific frequency band of the signal indicating the position in the vertical direction to pass through. [5] Device for non-invasive component analysis according to any one of claims 1 to 3, further comprising: a first gain controller, which is arranged between the light position detector and the differential detector and is capable of adjusting the gain of the signal indicating the position in the horizontal direction; and a second gain control, which is located between the light position detector and the differential detector and is able to adjust the gain of the signal indicating the position in the vertical direction. [6] Device for non-invasive component analysis according to any one of claims 1 to 5, wherein: The light position detector outputs an intensity of the emission probe light and The device for non-invasive component analysis further comprises a laser control unit for controlling the output of the probe light source based on the intensity of the emission probe light.

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