Device and method for measuring concentration of substance in blood

Abstract

To stably perform highly accurate measurement regardless of the state of an object to be measured or the fluctuation of the irradiation condition of a laser beam.SOLUTION: The in-blood-substance concentration measuring device 1 includes a target placement portion 10 on which a measurement target portion Mp of a living body Ob is placed, a light emission unit 20 that emits laser light L1 to the measurement target portion Mp, a photodetector 30 that receives reflection light of the emitted laser light from the measurement target portion Mp and detects the intensity of the reflection light L2, and an imaging lens 40 between the measurement target portion Mp and the photodetector 30. In the optical path Op2 from the measurement target portion Mp to the light detector 30, the laser light L2 propagates in a space except for a section in which the laser light L2 passes through the image-forming lens 40, and the image-forming lens 40 forms an image of the reflection light LA reflected from the measurement target portion Mp on the light detector 30.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to an apparatus and method for measuring the concentration of a substance contained in blood flowing through a blood vessel of a living body using a non-invasive measurement method. [Background technology]

[0002] In the prevention and treatment of lifestyle-related diseases, it is important to routinely monitor blood glucose levels, blood lipid levels, etc. In particular, for patients with diabetes, one of the lifestyle-related diseases, daily management of blood glucose levels by measuring the glucose concentration in the blood is required to prevent complications, and this has traditionally been achieved by invasive methods of drawing blood from patients and performing chemical analysis of the blood.

[0003] In response to this, simple, non-invasive methods have been proposed in recent years for optically measuring the state of blood in the body without blood sampling. For example, Patent Document 1 discloses a blood substance concentration measuring device that measures blood glucose concentration non-invasively and with a simple configuration by irradiating a living body with high-intensity mid-infrared light through a waveguide and guiding the reflected light to a photodetector via the waveguide. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2016 / 117520 Summary of the Invention [Problem to be solved by the invention]

[0005] However, the conventional blood substance concentration measuring device using a waveguide described in Patent Document 1 had the problem that the measured value fluctuated depending on the condition of the skin surface of the living body being measured or slight changes in the conditions of the irradiated laser light, making it difficult to perform stable and normal measurements.

[0006] The present disclosure has been made in consideration of the above-mentioned problems, and aims to provide a blood substance concentration measurement device and a blood substance concentration measurement method that can stably perform highly accurate measurements regardless of fluctuations in the state of the measurement object or the laser light irradiation conditions. [Means for solving the problem]

[0007] In order to achieve the above object, a blood substance concentration measuring device according to one embodiment of the present disclosure is a blood substance concentration measuring device that measures the concentration of a substance contained in the blood of a living organism, and is characterized in that it comprises an object placement section on which a living organism including a measurement target portion is placed, a light irradiation section that irradiates laser light onto the measurement target portion, a photodetector that receives reflected light of the irradiated laser light from the measurement target portion and detects the intensity of the reflected light, and a first lens between the measurement target portion and the photodetector in the optical path of the reflected light, and in the section from the object placement section to the photodetector in the optical path from the measurement target portion to the photodetector, the reflected light propagates through space except for the section that passes through the first lens, and the first lens forms an image of the reflected light on the photodetector. [Effects of the Invention]

[0008] According to an aspect of the present disclosure, a blood substance concentration measurement device and a blood substance concentration measurement method can stably perform highly accurate measurements regardless of fluctuations in the state of the measurement subject or the laser light irradiation conditions. [Brief explanation of the drawings]

[0009] [Figure 1] 1 is a schematic diagram showing the configuration of an apparatus 1 for measuring the concentration of a substance in blood according to a first embodiment. [Figure 2] 2(a) and 2(b) are enlarged cross-sectional views of part A in FIG. [Figure 3] 2 is a schematic diagram showing the configuration of a light irradiating unit 20 in the blood substance concentration measuring device 1. FIG. [Figure 4] 2 is a diagram for explaining an outline of a light path on the light receiving side in the blood substance concentration measuring device 1. FIG. [Figure 5](a) to (d) are graphs comparing the change in glucose concentration measured by the photodetector of a conventional non-invasive blood substance concentration measuring device 1X with the change in glucose concentration measured by an invasive measuring device over time. [Figure 6] 5(a) to 5(d) are diagrams showing the correlation between the glucose concentration measurement results obtained by the photodetector and the glucose concentration measurement results obtained by the invasive measurement device in FIGS. 5(a) to 5(d). [Figure 7] 10(a) to 10(c) are graphs comparing, over time, the change in the glucose concentration measured by the photodetector of the blood substance concentration measuring device 1 and the change in the glucose concentration measured by an invasive measuring device. [Figure 8] 7(a) to 7(c) are diagrams showing the correlation between the glucose concentration measurement results obtained by a photodetector and the glucose concentration measurement results obtained by an invasive blood glucose concentration measuring device in FIGS. 7(a) to 7(c). [Figure 9] FIG. 1 is a schematic diagram of an experimental device for measuring glucose concentrations measured by a photodetector while changing the light-receiving angle in a blood substance concentration measuring device 1. [Figure 10] 10(a) and 10(b) are diagrams showing changes in the measured glucose concentration when the light-receiving angle of the photodetector in the blood substance concentration measuring device 1 is changed. [Figure 11] (a) and (b) are graphs comparing the change in glucose concentration measured by a photodetector over time when the length of the light-receiving side optical path is changed in a blood substance concentration measuring device 1 and the change in glucose concentration measured by an invasive measuring device. [Figure 12] 10(a) and 10(b) are diagrams showing the correlation between the glucose concentration measurement results obtained by the photodetector and the glucose concentration measurement results obtained by the invasive measurement device in FIGS. 10(a) and 10(b). [Figure 13] (a) is a schematic diagram showing an overview of the optical path from the light irradiation unit 20X to the photodetector 30X in a conventional blood substance concentration measuring device 1X, and (b) is a schematic diagram showing an overview of the optical path from the light irradiation unit 20 to the photodetector 30 in a blood substance concentration measuring device 1. [Figure 14]10 is a schematic diagram showing the configuration of a blood substance concentration measuring device 1A according to a second embodiment. FIG. [Figure 15] 10 is a schematic diagram for explaining the operation of adjusting the optical path length from the measurement target portion Mp to the photodetector 30 by the blood substance concentration measuring device 1A. FIG. [Figure 16] 11 is a diagram showing changes in the lactate concentration measured by the photodetector when the wavelength of light emitted by the light irradiator is changed in the blood substance concentration measuring device according to the third embodiment. FIG. [Figure 17] FIG. 1 is a schematic diagram showing the configuration of a conventional blood substance concentration measuring device 1X. DETAILED DESCRIPTION OF THE INVENTION

[0010] <<How the present invention was developed>> In recent years, non-invasive methods for measuring the concentration of substances in the blood that do not involve blood sampling have been proposed for the purpose of managing the blood glucose levels of diabetic patients on a daily basis. Figure 17 is a schematic diagram showing the configuration of a conventional blood substance concentration measuring device 1X (hereinafter sometimes referred to as "device 1X") that uses a non-invasive method, as disclosed in Patent Document 1.

[0011] 17, the device 1X includes an object placement section 10X on which a living organism Ob to be examined is placed, a light irradiation section 20X that irradiates pulsed laser light L1 composed of mid-infrared light, a light guide section 90X in which an incident-side waveguide 91X and an exit-side waveguide 92X each formed of a through-hole are opened, a photodetector 30X that receives reflected light LX2 from the living organism Ob and detects its intensity, and a control section 60X for these components. Patent Document 1 describes that the device 1X can measure blood glucose levels non-invasively and with a simple configuration by irradiating high-intensity mid-infrared light.

[0012] However, as mentioned above, the inventors' experiments have revealed that with device 1X, which uses a non-invasive method, measurement values ​​fluctuate depending on the condition of the skin surface of the living body being measured and slight changes in the conditions of the irradiated laser light, making it difficult to perform stable and normal measurements.

[0013] According to the inventors' investigations, the reason for the fluctuation in measurement values ​​is believed to be that the light component reflected from the skin surface and the light component reflected from the inside of the body below the skin surface, where the blood glucose level is the target of measurement, are not separated, and the two components are detected as a mixture by the photodetector. To resolve this, for example, it is necessary to set up the optical system for each subject and measurement so that it is suited to the subject's biological conditions and measurement conditions. However, properly adjusting the optical system for each subject and each measurement requires advanced skill, and performing this adjustment for blood glucose level measurements that patients themselves perform on a daily basis would greatly reduce the convenience of non-invasive methods.

[0014] Therefore, the inventors have conducted extensive research into the configuration of an optical system that can stably achieve highly accurate measurements in a non-invasive method for measuring the concentration of a substance in blood, regardless of the state of the object being measured or variations in the conditions for irradiating the laser light, and have arrived at the following embodiment.

[0015] <<Outline of the mode for carrying out the present invention>> A blood substance concentration measuring device according to an embodiment of the present disclosure is a blood substance concentration measuring device that measures the concentration of a substance contained in the blood of a living organism, and is characterized in that it comprises an object placement section on which a living organism including a measurement target portion is placed, a light irradiation section that irradiates laser light onto the measurement target portion, a photodetector that receives reflected light of the irradiated laser light from the measurement target portion and detects the intensity of the reflected light, and a first lens between the measurement target portion and the photodetector in the optical path of the reflected light, and in the section from the object placement section to the photodetector in the optical path from the measurement target portion to the photodetector, the reflected light propagates through space except for the section that passes through the first lens, and the first lens forms an image of the reflected light on the photodetector.

[0016] This configuration reduces false signals (noise) caused by light scattered and reflected from the skin surface compared to conventional devices using a waveguide, improving the S / N ratio in optical measurements. This enables consistently accurate optical measurements regardless of the condition of the skin surface, which varies from subject to subject and from measurement to measurement. This provides a blood substance concentration measurement device that can stably perform highly accurate measurements regardless of the condition of the measurement target or the laser light irradiation conditions. As a result, a non-invasive and simple measurement method can be realized for blood glucose level measurements, which are performed daily by patients themselves, eliminating the need to appropriately adjust the optical system for each living body or each measurement.

[0017] In another aspect, in any of the above aspects, the light irradiating unit may be configured to irradiate the measurement target portion with laser light from the back side of the living body placement surface of the subject placement unit, and the photodetector may be configured to receive reflected light from the measurement target portion of the laser light irradiated on the back side of the subject placement unit.

[0018] With this configuration, it is possible to realize an optical system of an optical measurement device that can reduce false signal (noise) components caused by reflected light scattered on the skin surface.

[0019] In another aspect, in any of the above aspects, the measurement target portion may be a portion of the living body located inside the epidermis, and the first lens may be configured to transfer the irradiation area of ​​the laser light in the measurement target portion onto the light receiving surface of a detector.

[0020] With this configuration, the influence of the reflected light components from the skin surface, which are detected as noise, on the optical measurement is small, and the reflected light components from the biological part below the skin surface, which is the part to be measured, are imaged on the screen of the photodetector and reflected in the optical measurement by the photodetector, thereby enabling measurements to be performed with high reproducibility.

[0021] In another aspect, any of the above aspects may further include a second lens located between the light irradiating unit and the measurement target portion in the optical path of the laser light, and configured to focus the laser light on the measurement target portion, and in the section from the light irradiating unit to the target placement unit in the optical path from the light irradiating unit to the measurement target portion, the laser light may propagate through space except for the section passing through the second lens.

[0022] With this configuration, the laser light emitted from the light irradiator can be focused at a depth corresponding to a portion of the living body located inward from the epidermis, which corresponds to the portion to be measured that is a predetermined distance from the surface of the object placement unit. At this time, the irradiation range of the laser light can be reduced to a size corresponding to the portion to be measured.

[0023] In another aspect, in any of the above aspects, the light receiving surface of the photodetector may be configured to be spaced a predetermined distance from the first lens relative to the position where the reflected light is focused on the skin surface.

[0024] With this configuration, the light irradiation area in the measurement target portion, which corresponds to the portion of the living body located inside the epidermis, can be transferred to the position of the detector.

[0025] In another aspect, in any of the above aspects, the position of the photodetector may be varied to vary the depth of the measurement target portion from the skin surface.

[0026] With this configuration, the optical path length L on the light receiving side can be changed by adjusting the position of the photodetector, and it is also possible to accommodate measurement targets with thick skin.

[0027] In another aspect, in any of the above aspects, an incident angle of the laser light on the measurement target portion may be different from an exit angle of the optical path from the measurement target portion to the photodetector.

[0028] With this configuration, it is possible to suppress the influence of specular reflection of incident light.

[0029] In another aspect, in any of the above aspects, the emission angle of the optical path from the measurement target portion to the photodetector may be greater than or equal to 0 degrees and less than or equal to 90 degrees with respect to a normal to the surface on which the living body is placed in the target placement portion, and may be configured to be different from the incident angle of the laser light to the measurement target portion with respect to the normal.

[0030] In another aspect, in any of the above aspects, the angle of incidence of the laser light on the measurement target portion may be 45 degrees or more with respect to a normal to the surface of the target placement portion on which the living body is placed, and the angle of emission of the light path from the measurement target portion to the photodetector may be 0 degrees or more and 40 degrees or less with respect to the normal.

[0031] With this configuration, an optical system capable of stable measurement can be realized in which light absorption by glucose is relatively large, there is no increase in signal due to specular reflection, and the light receiving side optical system and the light emitting side optical system can be constructed.

[0032] In another aspect, in any of the above aspects, the wavelength of the laser light may be a predetermined wavelength selected from the range of 2.5 μm or more and 12 μm or less.

[0033] This configuration allows measurement of blood glucose concentration, as absorption by glucose is greater than that of conventional near-infrared light. Furthermore, since the transmittance into the body is lower than that of near-infrared light conventionally used to measure blood glucose levels, only the epidermis is observed, resulting in the effect of being less susceptible to the influence of other biological components present deep in the skin.

[0034] In another aspect, in any of the above aspects, the wavelength of the laser light may be modulated to vary the types of blood components that can be detected.

[0035] With this configuration, it is possible to detect a plurality of different types of blood components by selectively irradiating laser light of different wavelengths using the same measuring device.

[0036] In another aspect, in any of the above aspects, the wavelength of the laser light may be a predetermined wavelength selected from the range of 6.0 μm to 12 μm, and the blood component may be glucose. In this case, the wavelength may be in the range of −0.05 μm to +0.05 μm from 7.05 μm, 7.42 μm, 8.31 μm, 8.7 μm, 9.0 μm, 9.26 μm, 9.57 μm, 9.77 μm, 10.04 μm, or 10.92 μm.

[0037] With this configuration, since glucose has a higher absorption rate and a lower transmittance than near-infrared light, only the epidermis can be observed, and blood glucose concentration can be stably measured.

[0038] In another embodiment, in any of the above embodiments, the wavelength of the laser light may be a predetermined wavelength selected from the range of 5.0 μm to 12 μm, and the blood component may be lactic acid. In this case, the wavelength may be in the range of −0.05 μm to +0.05 μm from 5.77 μm, 6.87 μm, 7.27 μm, 8.23 ​​μm, 8.87 μm, or 9.55 μm.

[0039] With this configuration, the blood lactate concentration can be measured.

[0040] In another aspect, in any of the above aspects, the photodetector may comprise an infrared sensor that outputs the intensity of the reflected light as a one-dimensional value, and may be configured to be positionable so that its relative positional relationship with respect to the measurement target portion is equivalent to that of the photodetector, and may be configured to include a two-dimensional imaging means that receives reflected light reflected from the measurement target portion and detects whether an image based on the reflected light is formed.

[0041] With this configuration, the process of adjusting the optical path length from the measurement target portion to the photodetector in order to image the reflected light from the measurement target portion on the photodetector can be performed by replacing the photodetector with a two-dimensional imaging means.

[0042] In another aspect, in any of the above aspects, the photodetector may be configured as a two-dimensional infrared imaging element array having a plurality of light receiving elements capable of detecting mid-infrared light arranged in a matrix on a light receiving surface.

[0043] With this configuration, it is possible to use the photodetector itself to adjust the optical path length from the measurement target portion to the photodetector in order to image the reflected light from the measurement target portion onto the photodetector.

[0044] In another aspect, in any of the above aspects, the subject placement portion may have a through hole opened in the area where the surface of the living body comes into contact, the laser light is irradiated onto the surface of the living body through the through hole, and the reflected light may be received by the photodetector through the through hole.

[0045] With this configuration, total reflection on the surface of the living body Ob can be suppressed, and furthermore, the laser light emitted from the light emitting unit can be directly irradiated onto the surface of the living body, thereby improving the intensity of the laser light.

[0046] In another aspect, in any of the above aspects, the subject placement portion may have a recess formed in the area where the surface of the living body comes into contact, and the laser light may pass through the subject placement portion and be irradiated onto the surface of the living body, and the reflected light may pass through the subject placement portion and be received by the photodetector.

[0047] This configuration makes it possible to suppress total reflection on the surface of the living body, and since there is no opening in the target placement section, it is possible to prevent dust, dirt, water vapor, etc. from entering the atmosphere in which optical systems such as the light irradiation section are located, thereby giving the target placement section a dustproof function.

[0048] Furthermore, a blood substance concentration measurement method according to an embodiment of the present disclosure may be a blood substance concentration measurement method for measuring the concentration of a substance contained in the blood of a living organism, and may include a subject placement step of placing a living organism including a measurement target portion; a light irradiation step of irradiating the measurement target portion with laser light from a light irradiation unit from the back side of the living organism placement surface of the subject placement unit; a step of using a first lens located on the back side of the subject placement unit between the measurement target portion and a photodetector to form an image of reflected light reflected from the measurement target portion on the photodetector; and a light detection step of receiving the reflected light with the photodetector and detecting the intensity of the reflected light.

[0049] With this configuration, highly accurate measurements can be performed stably regardless of fluctuations in the state of the measurement object or the irradiation conditions of the laser light.

[0050] In another aspect, in any of the above aspects, the light irradiation step may be configured to focus the laser light on the measurement target portion using a second lens located between the light irradiation unit and the measurement target portion.

[0051] With this configuration, the laser light emitted from the light irradiating unit can be focused at a depth corresponding to the measurement target portion of the living body, which is spaced a predetermined distance from the surface of the target placement unit.

[0052] In another aspect, in any of the above aspects, in the step of forming an image of the reflected light on a photodetector, the reflected light is propagated in space in a section from the object placement unit to the photodetector in the optical path from the measurement target portion to the photodetector, except for a section that passes through the first lens; and in the light irradiation step, the laser light may be propagated in space in a section from the light irradiation unit to the object placement unit in the optical path from the light irradiation unit to the measurement target portion, except for a section that passes through the second lens.

[0053] In another aspect, in any of the above aspects, in the light irradiation step, laser light may be irradiated onto the measurement target portion from the back side of the living body placement surface of the subject placement unit, and in the step of forming an image on the photodetector, reflected light from the measurement target portion of the irradiated laser light may be received on the back side of the subject placement unit.

[0054] With this configuration, it is possible to specifically realize the step of forming an image of the reflected light from the measurement target portion on the photodetector.

[0055] In another aspect, any of the above aspects may be configured to include, prior to the step of forming an image of the reflected light on the photodetector, a step of adjusting the optical path length from the measurement target portion to the photodetector so that the reflected light reflected from the measurement target portion forms an image on the photodetector.

[0056] With this configuration, the light reflected from the measurement target portion can be imaged on the photodetector.

[0057] In another aspect, in any of the above aspects, the step of adjusting the optical path length may be configured to be performed by having a two-dimensional imaging means positioned in a relative positional relationship with the measurement target portion equivalent to that of the photodetector receive reflected light reflected from the measurement target portion, and detecting whether an image based on the reflected light is formed.

[0058] With this configuration, the process of adjusting the optical path length from the measurement target portion to the photodetector in order to image the reflected light from the measurement target portion on the photodetector can be performed by replacing the photodetector with a two-dimensional imaging means.

[0059] First Embodiment A blood substance concentration measuring device 1 according to this embodiment will be described with reference to the drawings. In this specification, the positive height direction may be referred to as the "up" direction, and the negative height direction may be referred to as the "down" direction, and the surface facing the positive height direction may be referred to as the "front" side, and the surface facing the negative height direction may be referred to as the "back" side. Furthermore, the scale of the components in each drawing is not necessarily the same as the actual scale. In this specification, the symbol "to" used to indicate a range of values ​​includes both ends of the range. The materials, values, etc. described in this embodiment are merely examples of preferred materials, and are not intended to limit the scope of the present invention.

[0060] <Overall structure> The blood substance concentration measuring device 1 (hereinafter sometimes referred to as "device 1") is a medical device that non-invasively measures the concentration of a substance in the blood of a living organism at a measurement target portion of the living organism by irradiating the measurement target portion with laser light of a specific wavelength from a light source and detecting the intensity of the light reflected from the measurement target portion. The laser light used is light of a specific wavelength that can be absorbed by the substance to be measured. When the concentration of a substance in the blood is high, the intensity of the light reflected from the measurement target portion decreases due to absorption by the substance. Therefore, device 1 measures the concentration of a substance in the blood by measuring the intensity of the reflected light with a photodetector. In this embodiment, as an example, the blood substance to be measured is glucose, and the laser light used is light of a wavelength selected from mid-infrared light, which may be a predetermined wavelength selected from the range of 2.5 μm to 12 μm. More preferably, the predetermined wavelength may be selected from the range of 6.0 μm to 12 μm. Specifically, for example, the laser light may be 9.26±0.05 μm (9.21 μm to 9.31 μm). Alternatively, the wavelength may be within a range of -0.05 μm to +0.05 μm from 7.05 μm, 7.42 μm, 8.31 μm, 8.7 μm, 9.0 μm, 9.57 μm, 9.77 μm, 10.04 μm, or 10.92 μm. This allows the glucose concentration in epithelial interstitial fluid to be measured as a blood glucose level. In this case, it is necessary to measure the glucose concentration in interstitial fluid directly under the skin, and it is preferable to use mid-infrared light, which has high absorption and therefore does not penetrate deep into the body. Furthermore, using mid-infrared light is less affected by overtones and combination tones, allowing for more accurate glucose measurement than near-infrared light.

[0061] Fig. 1 is a schematic diagram showing the configuration of an apparatus 1 according to embodiment 1. As shown in Fig. 1, the apparatus 1 includes an object placement unit 10, a light irradiation unit 20, a photodetector 30, a condenser lens 50, an imaging lens 40, and a control unit 60.

[0062] <Each part configuration> The configuration of each part of the device 1 will be described below.

[0063] (Target placement section 10) The subject placement unit 10 is a plate-like guide member whose surface 10a is in contact with the surface of the skin of the living body Ob, thereby restricting the measurement target portion Mp of the living body Ob to a specified position and angle suitable for measurement. In this case, the surface 10a of the subject placement unit 10 serves as the living body placement surface. By covering the optical system of the subject placement unit 10, such as the light irradiation unit 20, with a housing (not shown) and providing the subject placement unit 10 on the outer periphery of the housing, the subject placement unit 10 can function as an irradiation window through which laser light L1 is irradiated from inside.

[0064] The subject mounting section 10 is made of a material that is transparent to mid-infrared light, which is the specific wavelength used for measurement, such as ZnSe, and may have an anti-reflective coating layer on its surface. A measurement position is marked on the surface 10a of the subject mounting section 10, and by aligning a living organism Ob containing a measurement target portion Mp with the measurement position and bringing the living organism Ob into contact with the surface 10a of the subject mounting section 10 with a predetermined pressure, the measurement target portion Mp, which is a portion of the living organism Ob located inside the epidermis, such as the dermis, can be maintained at a predetermined distance from the surface 10a of the subject mounting section 10.

[0065] The object placement unit 10 is arranged so that the laser light L1 emitted from the light irradiator 20 enters from the rear surface 10d, and the angle relative to the light irradiator 20 is regulated so that the incident angle θ of the optical axis L1 on the incident side of the front surface 10a is a predetermined angle. Here, the incident angle θ refers to the angle of the optical axis L1 relative to the normal to the front surface 10a of the object placement unit 10 on which the living body Ob is placed.

[0066] 2(a) and 2(b) are enlarged cross-sectional views showing the configuration of part A in FIG. 1. These are enlarged views showing the portion where the measurement target portion Mp of the living body Ob abuts against the object placement unit 10. As shown in FIG. 2(a), a recessed portion 10b may be formed in the surface 10a of the object placement unit 10 to form a gap between the surface 10a and the living body Ob. In this case, the laser light L1 irradiated from the light irradiator 20 passes through the bottom portion of the recessed portion 10b in the object placement unit 10 and is irradiated onto the surface of the living body Ob. The lack of an opening in the object placement unit 10 prevents dust, dirt, water vapor, and the like from entering the atmosphere in which the optical system, such as the light irradiator 20, is present, thereby providing the object placement unit 10 with a dustproof function.

[0067] By providing the recess 10b, an air layer is formed between the surface 10a of the target placement portion 10 and the living body Ob, which makes it possible to suppress total reflection at the surface of the living body Ob compared to when the living body Ob is in contact with the target placement portion 10. Furthermore, by providing the recess 10b, it is possible to make it easier for the living body Ob to come into close contact with the surface 10a of the target placement portion 10 in areas other than the recess 10b. In this embodiment, as an example, the thickness of the target placement portion 10 may be 500 μm, the width of the recess 10b may be 700 μm, and the thickness of the air layer in the recess 10b may be approximately 400 μm.

[0068] 2(b), an opening 10c may be formed in a region that contacts the surface of the living body Ob on the surface 10a of the target placement unit 10. The opening 10c allows the laser light L1 emitted from the light irradiating unit 20 to be irradiated onto the surface of the living body Ob through the opening 10c, which is a through-hole opened in the target placement unit 10.

[0069] By providing the opening 10c, an air layer can be formed in the area where the surface 10a of the object placement section 10 contacts the living body Ob, which can suppress total reflection at the surface of the living body Ob compared to when the living body Ob is in contact with the object placement section 10. Furthermore, by providing the opening 10c, it is possible to make it easier for the living body Ob to come into close contact with the surface 10a of the object placement section 10 around the opening 10c in the surface 10a. In this embodiment, as an example, the thickness of the object placement section 10 may be 500 μm, and the width of the opening 10b may be 700 μm.

[0070] (Light irradiation unit 20) The light irradiating unit 20 is a light source that irradiates the living body with laser light of a specific wavelength toward the measurement target portion Mp. In the blood substance concentration measuring device 1, the light irradiating unit 20 is arranged on the back surface 10d side of the living body placement surface 10a of the subject placement unit 10, and irradiates laser light from the back surface 10d side of the subject placement unit 10 toward the measurement target portion Mp of the living body Ob on the living body placement surface (front surface 10a) of the subject placement unit 10.

[0071] FIG. 3 is a schematic diagram showing the configuration of the light irradiator 20 in the blood substance concentration measuring device 1. As shown in FIG. 3, the light irradiator 20 includes a light source 21 that oscillates pump light L0, which has a wavelength shorter than pulsed mid-infrared light, and an optical parametric oscillator (OPO) 22 that converts the pump light L0 to a longer wavelength, amplifies the light, and emits it as laser light L1. In the OPO 22, the pump light L0 is incident on a nonlinear optical crystal contained therein, thereby oscillating light of two different wavelengths, generating a short-wavelength signal light and a long-wavelength idler light. The light irradiator 20 outputs the idler light as laser light L1 to a subsequent stage and uses it to measure blood glucose levels. The OPO 22 may have a configuration described in a known document, for example, Japanese Patent Application Laid-Open No. 2010-281891. Here, the wavelength oscillated by optical parametric oscillation is mid-infrared light, which is more highly absorbed by glucose than the near-infrared light conventionally used, and is set to 9.26 μm in this embodiment. This mid-infrared light has a lower transmittance into the body than the near-infrared light conventionally used to measure blood glucose levels, so only the epidermis is observed, resulting in less influence from other biological components present deeper within the body. Another advantage is that the measurement is less adversely affected by overlapping harmonics and combination tones of the normal vibration.

[0072] The light source 21 may be equipped with a Q-switched Nd:YAG laser (oscillation wavelength 1.064 μm) or a Q-switched Yb:YAG laser (oscillation wavelength 1.030 μm). This allows for pulsed oscillation of pump light L0, which has a wavelength shorter than mid-infrared light. The pump light L0 may have a pulse width of approximately 8 ns and a frequency of 10 Hz or higher, for example. Furthermore, a Q-switched Nd:YAG laser or Yb:YAG laser operates as a passive Q switch that performs a passive switching operation using a saturable absorber, allowing the light source 21 to be simplified and miniaturized.

[0073] 3, the optical parametric oscillator 22 includes an incident-side semi-mirror 221, an exit-side semi-mirror 222, and a nonlinear optical crystal 223. The nonlinear optical crystal 223 is disposed in an optical resonator in which the incident-side semi-mirror 221 and the exit-side semi-mirror 222 face each other. Light L01 transmitted through the incident-side semi-mirror 221 enters the nonlinear optical crystal 223 and is converted to light with a wavelength of 9.26 μm determined by the nonlinear optical crystal 223, and is optically parametrically amplified between the incident-side semi-mirror 221 and the exit-side semi-mirror 222. The amplified light is transmitted through the exit-side semi-mirror 222 and output as laser light L1.

[0074] AgGaS, which is suitable for wavelength conversion, is used under phase matching conditions in the nonlinear optical crystal 223. The wavelength of the oscillated laser light L1 can be adjusted by adjusting the type of nonlinear optical crystal 223 and the matching conditions. GaSe, ZnGeP2, CdSiP2, LiInS2, LiGaSe2, LiInSe2, LiGaTe2, etc. may also be used as the nonlinear optical crystal. The laser light L1 emitted from the optical parametric oscillator 22 has a repetition frequency corresponding to the pump light L0, for example, a pulse width of about 8 ns, and the short pulse width can achieve a high intensity peak output of 10 W to 1 kW.

[0075] In this way, the light source 21 and the optical parametric oscillator 22 are used in the light irradiation unit 20, and thus the light output is 10 times faster than that of a conventional light source that obtains a wavelength of 9.26 μm, such as a quantum cascade laser. 3 ~10 5 It is possible to obtain laser light L1 with an intensity about twice as high.

[0076] This configuration enables blood glucose measurement using mid-infrared light, which has low transmittance into the body.

[0077] (condenser lens 50) 1, a condenser lens 50 (sometimes referred to as a "second lens" in this specification) is disposed on an optical path Op1 of the laser light L1 from the light irradiator 20 to the measurement target portion Mp. The condenser lens 50 condenses the irradiated light onto the measurement target portion Mp of the living body Ob. In the section of the optical path Op1 from the light irradiator 20 to the rear surface 10d of the object placement portion 10a, the laser light L1 is configured to propagate through space, such as gas, except for the section passing through the condenser lens 50. The condenser lens 50 is optically designed so that the laser light L1 emitted from the light irradiator 20 is condensed at a depth corresponding to the measurement target portion Mp of the living body Ob, for example, the dermis or other biological portion located inward from the epidermis, a predetermined distance from the surface 10a of the object placement portion 10. The incident angle θ of the laser light L1 onto the measurement target portion Mp is determined by the angle of the light irradiator 20 with respect to the surface 10a of the target placement portion 10 and the refraction angle of the laser light L1 incident on the target placement portion 10. In this embodiment, the incident angle θ may be, for example, 45 degrees or more, or may be 60 degrees or more and 70 degrees or less.

[0078] At this time, a beam splitter (not shown) made of a semi-transparent mirror may be disposed between the light irradiation unit 20 and the condenser lens 50 to split off a portion of the laser light L1 as a reference signal, and a monitor photodetector (not shown) may be used to detect changes in the intensity of the laser light L1, which may then be used for normalizing the detection signal in the photodetector 30. The output of the photodetector 30 can be compensated based on the fluctuations in the intensity of the laser light L1.

[0079] The laser light L1 that passes through the focusing lens 50 passes through the object placement section 10 and enters the living body Ob, passes through the epithelial stromal tissue of the living body, is scattered or diffusely reflected, and passes through the object placement section 10 again as reflected light L2, which is emitted toward the photodetector 30.

[0080] (Imaging lens 40) 4 is a diagram for explaining an overview of the light-receiving-side optical path in the blood substance concentration measuring device 1, and is a schematic diagram depicting the measurement target portion Mp of the living body Ob and the screen 30a of the photodetector 30 in a planar view. As shown in FIGS. 1 and 4, an imaging lens 40 (sometimes referred to as a "first lens" in this specification) is arranged in the optical path Op2 of the reflected light L2 from the measurement target portion Mp of the living body Ob to the photodetector 30 to form an image of the reflected light L2 diffusely reflected at the measurement target portion Mp of the living body Ob on the photodetector 30. In the section of the optical path Op2 from the back surface 10a of the object placement unit 10 to the photodetector 40, the reflected light L2 is configured to propagate through space, such as gas, except for the section passing through the condenser lens 50.

[0081] The imaging lens 40 is optically designed so that an image Im1 in a range corresponding to the measurement target portion Mp of the living body Ob is diffusely reflected and formed as reflected light L2 by the imaging lens 40 onto the screen 30a of the photodetector 30 as an image Im2.

[0082] In this embodiment, the distance Op21 between the center of the imaging lens 40 and the measurement target portion Mp of the living body Ob and the distance Op22 between the screen 30a of the photodetector 30 and the center of the imaging lens 40 are set to equivalent lengths, and a positional relationship is established such that an image Im1 at a depth corresponding to the measurement target portion Mp of the living body Ob irradiated with mid-infrared light, for example, a portion of the living body located inside the epidermis such as the dermis (hereinafter sometimes referred to as the "inner portion of the living body"), is transferred as an image Im2 of equivalent size onto the screen 30a of the photodetector 30. When the focal length with respect to the focus Fp of the imaging lens 40 is F, the distances Op21 and Op22 may both be 2F.

[0083] However, the lengths of distances Op21 and Op22 are not limited to those described above, and the magnifications of distances Op21 and Op22 may be set so that the image Im1 of the target placement portion 10 irradiated with mid-infrared light fits just within the screen 30a of the photodetector 30, and the imaging lens 40 may be set to achieve that magnification.

[0084] The incident angle of the reflected light L2 onto the imaging lens 40 is determined by the angle of the imaging lens 40 with respect to the surface 10a of the target placement section 10 and the refraction angle of the reflected light L2 emitted from the target placement section 10. In this embodiment, the incident angle may be, for example, between 0 degrees and 40 degrees, and more preferably between 20 degrees and 30 degrees.

[0085] (Photodetector 30) The photodetector 30 is a mid-infrared sensor that receives reflected light from the measurement target portion Mp of the irradiated laser light L1 and detects the intensity of the reflected light. In the blood substance concentration measuring device 1, the photodetector 30 is disposed on the back surface 10d of the living body placement surface 10a of the subject placement unit 10, and is configured to receive reflected light from the measurement target portion Mp of the living body Ob on the living body placement surface (front surface 10a) from the back surface 10d side of the subject placement unit 10. The photodetector 30 outputs an electrical signal corresponding to the intensity of the received reflected light. The photodetector 30 may be, for example, an infrared sensor consisting of a single element that outputs the intensity of the reflected light as a one-dimensional voltage value.

[0086] In the blood substance concentration measuring device 1, the light irradiator 20 increases the intensity of the irradiated laser light L1, and the imaging lens 40 forms an image of the reflected light from the measurement target portion Mp on the photodetector 30. This allows the photodetector 30 to receive reflected light with a sufficiently high intensity relative to background light, achieving a high S / N ratio and enabling highly accurate measurements. Because the laser light L1 and the reflected light L2 are monochromatic and highly intense, the only processing required by the photodetector 30 is to detect the light intensity. Unlike photoacoustic optics using quantum cascade lasers, spectral analysis based on wavelength sweeping or multivariate analysis is not required. This reduces the required detection accuracy, and a simpler method, such as electronic cooling, can be used.

[0087] It should be noted that a liquid nitrogen-cooled HgCdTe infrared detector may be used as the photodetector 30. In this case, by cooling the detector to approximately 77 K with liquid nitrogen, the intensity of the reflected light L2 can be detected with a higher S / N ratio.

[0088] (control unit 60) The control unit 60 is electrically connected to the light irradiation unit 20 and the photodetector 30, drives the light source 21 of the light irradiation unit 20 to oscillate pulsed pump light L0, and detects the light intensity of the reflected light L2 based on the output signal from the photodetector 30 to calculate the glucose concentration in the measurement target portion Mp of the living body Ob.

[0089] Alternatively, the control unit 60 may input the output of the monitor photodetector, and as described above, even if the intensity of the laser light L1 emitted from the light irradiation unit 20 fluctuates, the control unit 60 may calculate the glucose concentration by compensating for the effect of fluctuations in the intensity of the laser light L1 by normalizing the output of the photodetector 30 using the output of the monitor photodetector.

[0090] <Evaluation test> A performance evaluation test was carried out using the blood substance concentration measuring device 1 according to the embodiment. The results are described below.

[0091] (Test 1: Evaluation of Examples and Comparative Examples of Blood Substance Concentration Measuring Device 1) [Test equipment and conditions] As an example, the blood substance concentration measuring device 1 according to the embodiment shown in Fig. 1 was used. The device conditions for the blood substance concentration measuring device 1 are as follows.

[0092] (1) The object placement unit 10 was placed horizontally, and mid-infrared laser light was emitted upward from the light irradiation unit 20 at a launch angle of 24.5 degrees, and irradiated onto a measurement position marked from below the object placement unit 10. At this time, the condenser lens 50 reduced the irradiation range of the laser light L1 to a size corresponding to the measurement position.

[0093] (2) The subject's fingertip was placed on the upper surface 10a of the object placement section 10, and the incident angle was set to 65.5 degrees.

[0094] (3) An image of the measurement target portion Mp of the living body Ob irradiated with mid-infrared light was transferred by the imaging lens 40 disposed below the object mounting portion 10 and formed on the photodetector 30. When the focal length of the imaging lens 40 is F, the distance between the screen 30a of the photodetector 30 and the center of the imaging lens 40, and the distance between the center of the imaging lens 40 and the measurement target portion Mp of the living body Ob are both set to 2F, and a positional relationship was established such that an image Im1 of a depth corresponding to the portion of the living body located inward from the epidermis, which corresponds to the measurement target portion Mp, is transferred to the photodetector 30 at an equivalent size.

[0095] (4) The angle of the optical path Op2 between the photodetector 30 and the imaging lens 40 was set to an angle inclined 25 degrees clockwise from the vertical direction of the object placement unit 10.

[0096] As a comparative example, a conventional blood substance concentration measuring device 1X disclosed in Patent Document 1 shown in FIG. 17 was used.

[0097] [Test method] (1) The subject ingested an aqueous solution containing 40 g of glucose (the time of ingestion was set as the measurement start time 0 minutes), placed the subject's fingertip on the upper surface 10a of the subject placement unit 10, and continuously performed optical measurements according to the example and comparative example. In the optical measurements, mid-infrared laser light was irradiated for a certain period of time, and the blood glucose level was calculated from the change in the intensity of the mid-infrared light when irradiated onto the human body.

[0098] (2) In parallel with the optical measurements, blood glucose levels were measured by self-monitoring of blood glucose (SMBG) from the subjects.

[0099] (3) Optical measurement and blood glucose measurement by self-sampling were repeated at regular intervals (10 to 15 minutes), and the measured values ​​were plotted over time.

[0100] [Test Results] First, the results obtained by the conventional device 1X, which is a comparative example, will be described.

[0101] Figures 5(a) to (d) are graphs comparing, over time, the changes in the glucose concentration measured by the photodetector of conventional device 1X and the changes in the glucose concentration measured by an invasive measuring device according to a comparative example. Figures 6(a) to (d) are graphs showing the correlation between the glucose concentration measurement results by the photodetector and the glucose concentration measurement results by the invasive measuring device in Figures 5(a) to (d).

[0102] 5(a) to 5(d) show the results of tests conducted on the same subject on different test days.

[0103] After ingesting the aqueous solution, blood glucose levels measured by SMBG rise over time and then fall.

[0104] In Figure 5(a), the detected light intensity by optical measurement decreased and then increased over time after ingestion of the aqueous solution due to light absorption associated with an increase in blood glucose concentration, and a negative correlation was confirmed with the blood glucose level measurement results by SMBG (Figure 6(a)).

[0105] However, in the results shown in Figure 5(b)(c) conducted on different test days, there was no tendency for blood glucose levels to decrease and then increase over time after ingestion of the aqueous solution, and the correlation with the blood glucose level measurement results by SMBG was low (Figure 6(a)(c)). Alternatively, in the results shown in Figure 5(d), there was a tendency for blood glucose levels to decrease and then increase over time after ingestion of the aqueous solution, but the negative correlation was small, resulting in an extremely small response (Figure 6(d)).

[0106] As described above, with the conventional device 1X according to the comparative example, normal measurements could not be performed depending on the test day even under the same conditions.

[0107] Next, the results obtained by the blood substance concentration measuring device 1 according to the example will be described.

[0108] Figures 7(a) to (c) are diagrams comparing, over time, the changes in the glucose concentration measured by the photodetector of the blood substance concentration measuring device 1 and the changes in the glucose concentration measured by an invasive measuring device. Figures 8(a) to (c) are diagrams showing the correlation between the glucose concentration measurement results by the photodetector and the glucose concentration measurement results by the invasive blood glucose concentration measuring device in Figures 7(a) to (c).

[0109] 7(a) to 7(c) show the results of tests conducted on the same subject on different test days.

[0110] In Figures 7(a) to (c), the detected light intensity from the measurements decreased over time after ingestion of the aqueous solution due to light absorption associated with an increase in blood glucose concentration, and then increased.When compared with the blood glucose level measurement results using SMBG, a high negative correlation was confirmed in Figure 8(b), and a negative correlation was also confirmed in Figures 8(a) and (c).

[0111] From the above results, it was confirmed that the blood substance concentration measuring device 1 of the embodiment can obtain stable measurement results that are highly correlated with the blood glucose level measurement results by SMBG compared to the comparative example in repeated experiments conducted on different test days.

[0112] (Test 2: Evaluation test with varying light receiving angle φ of the photodetector) [Test equipment and conditions] Optical measurements were performed by changing the angle φ of the optical path on the light receiving side.

[0113] 9 is a schematic diagram of an experimental device for measuring glucose concentration values ​​measured by a photodetector by changing the angle and optical path length of the light-receiving side of a blood substance concentration measuring device 1. Using the blood substance concentration measuring device 1 of the embodiment in Test 1, optical measurements were performed under conditions in which the angle φ (hereinafter sometimes referred to as "angle φ") of the optical path Op2 of the photodetector 30 and the imaging lens 40 was varied from 0 degrees to 40 degrees clockwise (vertical direction in FIG. 9) based on the normal to the surface of the subject mounting unit 10 on which the living body Ob is placed. Other device conditions and test methods were the same as in Test 1.

[0114] [Test Results] Figures 10(a) and (b) show the change in the measured glucose concentration when the light receiving angle of the photodetector in the blood substance concentration measuring device 1 is changed, where Figure 10(a) shows the relationship between the angle φ and the input / output ratio of the detected light in optical measurement, and (b) shows the experimental results showing the variation in the measurement results for each measurement at each angle φ.

[0115] As shown in Figure 10(a), absorption was observed when the angle φ was between 0 and 40 degrees, with the greatest absorption observed between 20 and 30 degrees. It was also confirmed that the signal increased when the angle exceeded 40 degrees. When the angle φ increased beyond 40 degrees, it became closer to the angle of specular reflection of the incident light, which is considered unsuitable for use in optical measurements. Furthermore, since an input / output ratio of 0.2 or less is preferable from the standpoint of measurement accuracy, it is even more preferable that the angle φ be 30 degrees or less. Furthermore, since an input / output ratio of less than 0.1 is undesirable from the standpoint of the S / N ratio of the measurement signal, it is even more preferable that the angle φ be 20 degrees or more.

[0116] Furthermore, as shown in Figure 10(b), the variation was small when the angle φ was 0 degrees, the smallest when it was 25 degrees, and the largest when it was 45 degrees. This is thought to be because when the angle φ is 45 degrees or more, it approaches the angle of specular reflection of the incident light.

[0117] Furthermore, when the angle φ is 45 degrees or more, measurement is difficult due to the device configuration. When the angle φ is less than 20 degrees, the light receiving optical system and the light emitting optical system are close to each other, which makes it difficult to lay out the optical system of the blood substance concentration measuring device 1.

[0118] From the above results, it is considered that the angle φ of the optical path on the light receiving side is preferably between 0 and 40 degrees, and even more preferably between 20 and 30 degrees. Furthermore, in order to suppress the influence of specular reflection of the incident light, it is preferable that the incident angle of the laser light is different from the output angle to the photodetector.

[0119] (Test 3: Evaluation test with varying optical path length L on the light receiving side) [Test equipment and conditions] Optical measurements were performed by changing the optical path length L on the light receiving side.

[0120] Using the blood substance concentration measuring device 1 of the embodiment in Test 1, optical measurement was performed under conditions in which the distance L between the screen 30a of the photodetector 30 and the center of the imaging lens 40 and the distance L between the center of the imaging lens 40 and the measurement target portion Mp of the living body Ob (hereinafter sometimes referred to as the "optical path length L") were varied to 2F-0.5 [mm], 2F [mm], and 2F+0.5 [mm] relative to the focal length F of the imaging lens 40. Other device conditions and test methods were the same as in Test 1.

[0121] [Test Results] Figures 11(a) and (b) are graphs comparing, over time, the changes in the glucose concentration measured by a photodetector when the length of the light-receiving side optical path is changed in the blood substance concentration measuring device 1 and the changes in the glucose concentration measured by an invasive measuring device.

[0122] Figures 7(a), 11(a), and (b) show the test results when the optical path length L was set to 2F [mm], 2F-0.5 [mm], and 2F+0.5 [mm], respectively.

[0123] When the optical path length L was set to 2F [mm], the detected light intensity measured, as shown in Figure 7(a) above, decreased and then increased over time after ingestion of the aqueous solution due to light absorption associated with an increase in blood glucose concentration. When compared with the blood glucose level measurement results using SMBG, a high negative correlation was confirmed in Figure 8(a).

[0124] In contrast, when the optical path length L was set to 2F-0.5 [mm] and 2F+0.5 [mm], the detected light intensity measured did not show a tendency to decrease and then increase over time after ingestion of the aqueous solution due to light absorption associated with an increase in blood glucose concentration, as shown in Figures 11(a) and 11(b). In Figure 11(a), the response to changes in blood glucose level was extremely small, and in Figure 11(b), almost no response to changes in blood glucose level was observed. In addition, the correlation with the blood glucose level measurement results by SMBG was low (Figures 12(a) and 12(b)).

[0125] From the above results, it is considered preferable that the optical path length L on the light receiving side, i.e., the distance L between the screen 30a of the photodetector 30 and the center of the imaging lens 40 and the distance L between the center of the imaging lens 40 and the measurement target portion Mp of the living body Ob, be a length corresponding to the imaging position of the imaging lens 40 (twice the focal length F). It is considered that reflected light from the measurement target portion Mp of the living body Ob, which corresponds to the part of the living body located inside the epidermis, is imaged on the screen 30a of the photodetector 30. In this case, the distance between the upper surface 10a of the subject mounting portion 10, which corresponds to the skin surface, and the center of the imaging lens 40 is approximately 50 mm, which is approximately 0.8 mm shorter than the distance L.

[0126] <Effects of the Blood Substance Concentration Measuring Device 1> As described above, according to the results of Test 1, the conventional device 1X using a waveguide, which is a comparative example, showed poor reproducibility, in that normal measurements could not be performed depending on the test date, even under the same conditions.

[0127] In contrast, it was confirmed that optical measurement using the blood substance concentration measuring device 1 according to the embodiment provides measurement results that are highly correlated with blood glucose level measurement results by SMBG and highly reproducible, compared to the conventional device 1X according to the comparative example. It is believed that the blood substance concentration measuring device 1 enables highly reproducible optical measurement by adopting an optical system that includes an imaging lens 40 between the measurement target portion Mp and the photodetector 30 and that forms an image of reflected light L2 reflected from the measurement target portion Mp on the photodetector 30.

[0128] The reason for this is that the conventional device 1X using the waveguide according to the comparative example was unable to separate components from the skin surface and components absorbed by blood sugar under the skin, and there were cases where normal measurement was not possible due to the condition of the skin surface or slight changes in the laser irradiation conditions, whereas with the blood substance concentration measuring device 1 according to the embodiment, signals from under the skin are collected on the optical sensor, reducing the impact of slight changes in the measurement conditions on the measurement results, and it is thought that stable and correct measurement results can be obtained.

[0129] A specific description will be given below with reference to the drawings.

[0130] FIG. 13(a) is a schematic diagram showing an outline of the optical path from the light irradiator 20X to the photodetector 30X in a conventional blood substance concentration measuring device 1X. As shown in FIG. 13(a), in the conventional device 1X using a waveguide, laser light LX1 irradiated from the light irradiator 20 enters the living body Ob at an incident angle θ along an optical path parallel to the incident-side waveguide 91X toward the measurement target portion Mp of the living body Ob. At this time, in addition to a reflected light component (Im11) from the internal portion of the living body below the skin surface to be measured, which may be absorbed by blood glucose, a reflected light component (Im12) from the skin surface is also generated. In the conventional device 1X using a waveguide, these reflected light components (Im11, Im12) enter the exit-side waveguide 92X and are guided to the screen 30Xa of the photodetector 30.

[0131] That is, with the conventional device 1X, the reflected light component (Im12) from the skin surface and the reflected light component (Im11) from the inner part of the living body below the skin surface are not separated, and the photodetector detects both components mixed together. As a result, the measurement results include the reflected light component (Im12) other than the reflected light component (Im11) from the inner part of the living body below the skin surface that should be measured, which is thought to increase the factors of variation and result in low reproducibility.

[0132] 13(b) is a schematic diagram showing an outline of the optical path from the light irradiator 20 to the photodetector 30 in the blood substance concentration measuring device 1. As shown in Fig. 13(b), in the blood substance concentration measuring device 1 as well, the laser light L1 irradiated from the light irradiator 20 enters the living body Ob at an incident angle θ along an optical path toward the test target portion Mp of the living body Ob, and is absorbed by blood glucose and generates a reflected light component (Im11) from the inside of the living body below the skin surface that should be the measurement target portion Mp, as well as a reflected light component (Im12) from the skin surface.

[0133] However, in the blood substance concentration measuring device 1, the imaging lens 40 is configured so that, of these reflected light components (Im11, Im12), mainly the reflected light component (Im11) from the inside of the living body is imaged on the screen 30a of the photodetector 30. The reflected light component (Im12) from the skin surface enters the imaging lens 40, but because the angle of incidence on the imaging lens 40 is different from that of the reflected light component (Im11) from the inside of the living body, the light is either guided outside the range of the screen 30a of the photodetector 30, or even if the light is guided within the range of the screen 30a of the photodetector 30, it does not form an image (is blurred), resulting in a decrease in the amount of light and a decrease in the signal strength detected by the photodetector 30. As a result, the reflected light component (Im12) from the skin surface, which is detected as noise, has little effect on the optical measurement.

[0134] In other words, in the blood substance concentration measuring device 1, the reflected light component (Im11) from the inner part of the body below the surface of the skin, which is the main measurement target, is imaged on the screen 30a of the photodetector 30 and reflected in the optical measurement by the photodetector 30, and therefore it is thought that the measurement results have a high correlation with the blood glucose level measurement results by SMBG and are highly reproducible compared to the comparative example.

[0135] Thus, compared to conventional devices 1X using waveguides, the blood substance concentration measuring device 1 can reduce false signal (noise) components caused by reflected light scattered on the skin surface, improving the S / N ratio in optical measurements. This also enables consistently accurate optical measurements regardless of the condition of the skin surface, which varies from subject to subject and from measurement to measurement. Furthermore, by adjusting the position of the photodetector, the optical path length L on the light receiving side can be changed, making it possible to accommodate measurement targets with thick skin.

[0136] <Summary> As described above, the blood substance concentration measuring device 1 according to the first embodiment is a blood substance concentration measuring device 1 for measuring the concentration of a substance contained in the blood of a living organism Ob, and includes an object placement section 10 on which a measurement target portion Mp of the living organism Ob is placed, a light irradiating section 20 that irradiates the measurement target portion Mp with laser light L1 from the back surface 10d side of the living organism placement surface (front surface 10a) of the object placement section 10, and a light irradiating section 20 that irradiates the irradiated laser light L1 from the back surface 10d side of the measurement target portion Mp. The device is equipped with a photodetector 30 that receives light L2 and detects the intensity of the reflected light L2, and an imaging lens 40 between the measurement target portion Mp and the photodetector 30, and in the section from the target mounting portion 10 to the photodetector 40 on the optical path Op2 from the measurement target portion Mp to the photodetector 30, the laser light L2 propagates through space except for the section that passes through the imaging lens 40, and the imaging lens 40 forms an image of the reflected light L2 reflected from the measurement target portion Mp on the photodetector 30.

[0137] This configuration enables stable, highly accurate measurements to be performed regardless of fluctuations in the state of the measurement target or the laser light irradiation conditions. As a result, in blood glucose measurement, which is performed daily by patients themselves, work such as adjusting the optical system for each living body or each time a measurement is performed can be eliminated, realizing a non-invasive and simple measurement method.

[0138] Second Embodiment The blood substance concentration measuring device 1 according to embodiment 1 comprises a target placement section 10, a light irradiation section 20, a photodetector 30, and an imaging lens 40, and is configured such that the imaging lens 40 forms an image of reflected light L2 reflected from the measurement target portion Mp on the photodetector 30.

[0139] However, the specific configuration for the imaging lens 40 to image the reflected light L2 reflected from the measurement target portion Mp onto the photodetector 30 is not limited to these, and other configurations may be used.

[0140] Hereinafter, a blood substance concentration measuring device 1A according to embodiment 2 will be described with reference to the drawings. Fig. 14 is a schematic diagram showing the configuration of the blood substance concentration measuring device 1A according to embodiment 2. In Fig. 14, the same components as those in the blood substance concentration measuring device 1 are given the same numbers, and their description will be omitted.

[0141] The blood substance concentration measuring device 1A of embodiment 2 differs from embodiment 1 in that, in addition to the configuration of the blood substance concentration measuring device 1, it is further configured to be positionable so that its relative positional relationship with respect to the measurement target portion Mp is equivalent to that of the photodetector 30, and is equipped with a two-dimensional imaging means 71A that receives reflected light (Im11) reflected from the measurement target portion Mp and detects whether an image based on the reflected light (Im11) is formed.

[0142] The two-dimensional imaging means 71A is a two-dimensional infrared imaging element array in which a plurality of light-receiving elements capable of detecting mid-infrared light are arranged in a matrix on a light-receiving surface 71Aa. As shown in Fig. 14, the two-dimensional imaging means 71A is integrated with a photodetector 30 to form a light detection unit 70A, and the light detection unit 70A is configured to be slidable in a direction perpendicular to an optical path L2 from the measurement target portion Mp to the imaging lens 40. The two-dimensional imaging means 71A is positioned on the optical path L2 so that the relative positional relationship of the light-receiving surface 71Aa of the two-dimensional imaging means 71A to the measurement target portion Mp is equivalent to the relative positional relationship of the screen 30a of the photodetector 30 to the measurement target portion Mp.

[0143] With this configuration, the process of adjusting the optical path length from the measurement target portion Mp to the photodetector 30 in order to image the reflected light (Im11) from the measurement target portion Mp onto the photodetector 30 can be performed by replacing the photodetector 30 with a two-dimensional imaging means 71A.

[0144] FIG. 15 is a schematic diagram for explaining the operation of adjusting the optical path length from the measurement target portion Mp to the photodetector 30 by the blood substance concentration measuring device 1A.

[0145] In the optical path length adjustment process, first, as shown in Figure 15, the light receiving surface 71Aa of the two-dimensional imaging means 71A is positioned on the optical path L2 so that its relative positional relationship with the measurement target portion Mp is equivalent to the relative positional relationship of the screen 30a of the photodetector 30 with the measurement target portion Mp.

[0146] Next, in this state, the two-dimensional imaging means 71A receives the reflected light reflected from the measurement target portion Mp, and detects whether an image based on the reflected light is formed. If an image is not formed, the position of the two-dimensional imaging means 71A on the optical path L2 is gradually moved, and the detection of whether an image is formed is repeated.

[0147] Specifically, the focus position of the memory image changes as the two-dimensional imaging means 71A scans along the optical path L2. This is determined by image analysis, and the position of the two-dimensional imaging means 71A when the focus position coincides with the previously determined irradiation position is determined as the imaging position. Whether an image is formed or not is determined by mounting a scale graduated in 0.5 mm increments on the object placement unit 10, acquiring an image using the two-dimensional imaging means 71A, and detecting the focus position within the image, as shown in FIG. 15. In this case, the focus position may be, for example, the maximum point of the brightness distribution within the image.

[0148] 15, at position X1 on the scale, the focus position in the acquired image and the irradiation position of the laser light L1 are misaligned, and it is determined that an image is not formed. At position X2 on the scale, the focus position in the acquired image and the irradiation position of the laser light L1 are aligned, and it is determined that an image is formed. Then, the light detection unit 70A is gradually moved parallel to the optical path L2 until the focus position in the acquired image and the irradiation position of the laser light L1 are aligned on the optical path L2, and it is determined whether an image is formed.

[0149] After it is confirmed that an image has been formed, the two-dimensional imaging means 71A is returned to the photodetector 30, and the optical path length from the measurement target portion Mp to the photodetector 30 is determined.

[0150] As described above, the blood substance concentration measuring device 1A according to embodiment 2 is configured to be positionable so that its relative positional relationship with respect to the measurement target portion Mp is equivalent to that of the photodetector 30, and is configured to include a two-dimensional imaging means 71A that receives reflected light (Im11) reflected from the measurement target portion Mp and detects whether an image based on the reflected light (Im11) is formed.

[0151] This allows the step of adjusting the optical path length from the measurement target portion Mp to the photodetector 30, in order to image the reflected light (Im11) from the measurement target portion Mp on the photodetector 30, to be performed by replacing the photodetector 30 with the two-dimensional imaging means 71A. As a result, it is possible to easily construct a blood substance concentration measuring device 1A that can stably perform highly accurate measurements regardless of fluctuations in the state of the measurement target or the irradiation conditions of the laser light.

[0152] Third Embodiment In the blood substance concentration measuring devices 1 and 2 according to the first embodiment, the wavelength of the laser light L1 emitted by the light irradiating unit 20 is 9.26 μm, and the blood component to be detected is glucose.

[0153] However, the wavelength of the laser light L1 emitted by the light irradiating unit 20 may be varied depending on the type of blood component to be detected.

[0154] A blood substance concentration measuring device according to a third embodiment will now be described with reference to the drawings. The blood substance concentration measuring device according to the third embodiment is characterized in that the wavelength of the laser light L1 emitted by the light irradiator 20 may be 8.23±0.05 μm (8.18 μm or more and 8.28 μm or less), and the blood component is lactic acid. Alternatively, the wavelength may be in the range of −0.05 μm or more and +0.05 μm or less from 5.77 μm, 6.87 μm, 7.27 μm, 8.87 μm, or 9.55 μm.

[0155] 16 is a diagram showing changes in the lactate concentration measured by the photodetector when the wavelength of light emitted by light irradiator 20 is set to 8.23 ​​μm in the blood substance concentration measuring device according to embodiment 3. As shown in FIG. 16, it was confirmed that the measurement value obtained by optical measurement roughly correlates with the lactate level measurement result (comparison value) obtained by self-blood sampling.

[0156] In order to change the wavelength of the light emitted by the light irradiation unit 20, it is necessary to change the oscillation wavelength of the optical parametric oscillator 22 of the light irradiation unit 20 to a different mode, and the device can be realized by changing the phase matching condition of the nonlinear crystal 223 in the optical parametric oscillator 22, or by changing the optical parametric oscillator 22 with a different phase matching condition of the nonlinear crystal 223.

[0157] Furthermore, the light irradiation unit 20 may be configured to selectively use multiple optical parametric oscillators 22 and selectively irradiate laser light L1 of multiple wavelengths, thereby making it possible to make the device capable of measuring multiple types of blood components.

[0158] In this case, the blood substance concentration measuring device of embodiment 3 differs from a configuration that employs an optical system using a waveguide in which the width and thickness of the optical path vary depending on the wavelength of the guided light, and can share an optical system consisting of a focusing lens 50, a subject placement unit 10, an imaging lens 40, and a photodetector 30 capable of detecting mid-infrared light with measuring devices for other blood components such as glucose.

[0159] As described above, the blood substance concentration measuring device according to the third embodiment can detect different types of blood constituents by changing the wavelength of the laser light L1 emitted by the light irradiator 20. Alternatively, a plurality of different types of blood constituents can be detected by selectively irradiating laser light L1 of different wavelengths using the same measuring device. As a result, a measuring device that is even easier to use for measuring blood glucose levels that patients themselves measure on a daily basis can be realized.

[0160] <<Variations>> While the specific configuration of the present disclosure has been described above using the embodiments as examples, the present disclosure is not limited to the above embodiments except for the essential characteristic components thereof. For example, the present disclosure also includes forms obtained by various modifications to the embodiments and forms realized by arbitrarily combining the components and functions of each embodiment within the scope of the present invention.

[0161] (1) In the above embodiment, the blood substance concentration measuring device is exemplified by an optical system including an imaging lens 40 between the measurement target portion Mp and the photodetector 30. However, the blood substance concentration measuring device according to the present disclosure may be configured to image the reflected light L2 reflected from the measurement target portion Mp of the living body Ob on the photodetector 30, and the light receiving optical system may be modified as appropriate. For example, a configuration using multiple lenses or a configuration with a mirror disposed midway along the optical path may be used.

[0162] (2) In the above embodiment, glucose or lactic acid is used as an example of a blood component to be detected by the blood substance concentration measuring device. However, the blood components that can be detected by the blood substance concentration measuring device according to the present disclosure are not limited to those described above. By varying the wavelength of the laser light L1 emitted by the light irradiating unit 20 depending on the type of blood component, the device can be widely used for detecting other blood components.

[0163] (3) In the above embodiment, the photodetector 30 is an infrared sensor having a single light-receiving element capable of detecting mid-infrared light. However, the photodetector 30 may be a two-dimensional infrared imaging element array having a plurality of light-receiving elements capable of detecting mid-infrared light arranged in a matrix on its light-receiving surface. This allows the photodetector 30 itself to be used to adjust the optical path length from the measurement target portion Mp to the photodetector 30 so that the reflected light from the measurement target portion Mp forms an image on the photodetector 30. Specifically, in the optical path length adjustment step, the photodetector 30 receives the light reflected from the measurement target portion Mp and detects whether an image based on the reflected light has been formed. If an image has not been formed, the position of the photodetector 30 on the optical path L2 is gradually moved, and the detection of whether an image has been formed is repeated. This makes it possible to use the photodetector 30 itself to adjust the optical path length from the measurement target portion Mp to the photodetector 30, thereby simplifying the device compared to the second embodiment.

[0164] (4) In the above embodiment, in the blood substance concentration measuring device 1, the light irradiating unit 20 irradiates the measurement target portion Mp with laser light L1 from the back surface 10d of the living body placement surface (surface 10a) of the subject placement unit 10, and the photodetector 30 receives reflected light L2 from the measurement target portion of the irradiated laser light L1 on the back surface 10d of the subject placement unit 10.

[0165] However, the light irradiating unit 20 may be configured to irradiate the measurement target portion Mp with laser light L1 from the surface 10a side of the living body placement surface (surface 10a) of the target placement unit 10. The photodetector 30 may be configured to receive reflected light L2 from the measurement target portion of the irradiated laser light L1 on the surface 10a side of the target placement unit 10.

[0166] In this case, for example, the measurement target portion Mp of the living body Ob may be placed facing upward on the object placement portion 10, and a plate material through which the laser light L1 passes (transparent to the laser light) may be used to slightly compress the living body Ob from above, thereby determining the height of the measurement target portion Mp relative to the object placement portion 10 (and the light irradiation portion 20).

[0167] Alternatively, an optical means may be provided that detects the position of the measurement target portion Mp by measuring the time it takes for laser light to be emitted and reflected light from the measurement target portion Mp of the living body Ob to be received, and feedback may be provided, such as changing the direction of irradiation or focusing distance of the laser light L1 in measuring the concentration of a substance in the blood, based on the detected position information of the measurement target portion Mp.

[0168] With this configuration, the light irradiating unit 20 can irradiate the measurement target portion Mp with laser light L1 from the surface 10a side of the living body placement surface (surface 10a) without passing through the target placement unit 10, thereby measuring the concentration of a substance in the blood.

[0169] <<Additional Information>> The embodiments described above each illustrate a preferred specific example of the present invention. The numerical values, shapes, materials, components, component placement and connection configurations, steps, and step sequences shown in the embodiments are merely examples and are not intended to limit the present invention. Furthermore, among the components in the embodiments, those not described in the independent claims that represent the highest concept of the present invention are described as optional components that constitute more preferred embodiments.

[0170] The order in which the above methods are performed is merely an example for specifically explaining the present invention, and other orders may be used. Also, some of the above methods may be performed simultaneously (in parallel) with other methods.

[0171] In order to facilitate understanding of the invention, the scale of the components in the drawings of the above embodiments may differ from the actual scale. Furthermore, the present invention is not limited to the description of the above embodiments, and can be modified as appropriate within the scope of the gist of the present invention.

[0172] Furthermore, at least some of the functions of the embodiments and their modifications may be combined. [Industrial Applicability]

[0173] A blood substance concentration measuring device and a blood substance concentration measuring method according to one embodiment of the present disclosure can be widely used as medical equipment for measuring blood substance conditions such as blood glucose levels and blood lipid levels on a daily basis in the prevention and treatment of lifestyle-related diseases. [Explanation of symbols]

[0174] 1 Blood substance concentration measuring device 10, 10X target placement area 20, 20X light irradiation section 21 Light source 22 Optical Parametric Oscillator 221 Semi-transparent mirror on the entrance side 222 Output side semi-transparent mirror 223 Nonlinear Optical Crystals 30 Photodetector 40 Imaging lens (first lens) 50 Condenser lens (second lens) 70A Optical Detection Unit 71A 2D imaging means 90X light guide plate 91X Input side waveguide 92X Output waveguide

Claims

1. A blood substance concentration measuring device for measuring the concentration of a substance contained in the blood of a living body, a subject placement section on which a living body including a measurement target portion is placed; a light irradiation unit that irradiates the measurement target portion with laser light; a photodetector that receives reflected light of the irradiated laser light from the measurement target portion and detects the intensity of the reflected light; a first lens between the measurement target portion and the photodetector in the optical path of the reflected light; the reflected light propagates through space in a section from the object placement unit to the photodetector in the optical path from the measurement object portion to the photodetector, except for a section passing through the first lens; The first lens focuses the reflected light onto a photodetector. Blood substance concentration measuring device.

2. the light irradiating unit irradiates the measurement target portion with laser light from a rear side of the living body placement surface of the target placement unit; The photodetector receives the reflected light from the measurement target portion of the laser light irradiated on the back surface side of the target placement unit. The blood substance concentration measuring device according to claim 1 .

3. The measurement target portion is a portion of the living body located inside the epidermis, and the first lens transfers the irradiated area of ​​the laser light on the measurement target onto a light receiving surface of a detector. The blood substance concentration measuring device according to claim 1 or 2.

4. further comprising a second lens positioned between the light irradiation unit and the measurement target portion in the optical path of the laser light, the second lens focusing the laser light on the measurement target portion; In a section from the light irradiation unit to the measurement target portion in the optical path from the light irradiation unit to the target placement unit, the laser light propagates in space except for a section passing through the second lens. The blood substance concentration measuring device according to any one of claims 1 to 3.

5. The light receiving surface of the photodetector is spaced from the first lens by a predetermined distance from the position where the reflected light is focused on the skin surface. The blood substance concentration measuring device according to any one of claims 1 to 4.

6. The position of the photodetector is varied to vary the depth of the measurement target portion from the skin surface. The blood substance concentration measuring device according to any one of claims 1 to 5.

7. The incident angle of the laser light on the measurement target portion is different from the exit angle of the light path from the measurement target portion to the photodetector. The blood substance concentration measuring device according to any one of claims 1 to 6.

8. The emission angle of the optical path from the measurement target portion to the photodetector is between 0 degrees and 90 degrees with respect to a normal to the surface of the target placement unit on which the living body is placed, and is different from the incident angle of the laser light to the measurement target portion with respect to the normal. The blood substance concentration measuring device according to claim 7.

9. an incident angle of the laser light on the measurement target portion is 45 degrees or more with respect to a normal to a surface of the target mounting portion on which the living body is mounted; The emission angle of the optical path from the measurement target portion to the photodetector is 0 degrees or more and 40 degrees or less with respect to the normal line. The blood substance concentration measuring device according to claim 7.

10. The wavelength of the laser light is a predetermined wavelength selected from the range of 2.5 μm to 12 μm. The blood substance concentration measuring device according to any one of claims 1 to 9.

11. The wavelength of the laser light is modulated to vary the types of blood components that can be detected. The blood substance concentration measuring device according to claim 10.

12. The wavelength of the laser light is a predetermined wavelength selected from the range of 6.0 μm to 12 μm, and the blood component is glucose. The blood substance concentration measuring device according to claim 10.

13. The wavelength of the laser light is a predetermined wavelength selected from the range of 5.0 μm to 12 μm, and the blood component is lactic acid. The blood substance concentration measuring device according to claim 10.

14. the photodetector is an infrared sensor that outputs the intensity of the reflected light as a one-dimensional value; and a two-dimensional imaging means configured to be configurable so that its relative positional relationship with respect to the measurement target portion is equivalent to that of the photodetector, and which receives light reflected from the measurement target portion and detects whether an image based on the reflected light is formed. The blood substance concentration measuring device according to any one of claims 1 to 13.

15. The photodetector is a two-dimensional infrared sensor array in which a plurality of light receiving elements capable of detecting mid-infrared light are arranged in a matrix on a light receiving surface. The blood substance concentration measuring device according to any one of claims 1 to 13.

16. the subject placement portion has a through-hole formed in a region where the surface of the living body comes into contact; The laser light is irradiated onto the surface of the living body through the through-hole, The reflected light is received by the photodetector through the through-hole. The blood substance concentration measuring device according to any one of claims 1 to 15.

17. the subject placement portion has a recess formed in a region where the surface of the living body comes into contact; the laser light is transmitted through the object placement unit and irradiated onto the surface of the living body; The reflected light is transmitted through the object placement portion and received by the photodetector. The blood substance concentration measuring device according to any one of claims 1 to 15.

18. A method for measuring the concentration of a substance in blood of a living body, comprising: a subject placement step of placing a living body including a measurement target portion; a light irradiation step of irradiating the measurement target portion with laser light from a light irradiation unit; forming an image of the light reflected from the measurement target portion onto the photodetector using a first lens positioned between the measurement target portion and the photodetector; a light detection step of receiving the reflected light with the light detector and detecting the intensity of the reflected light. Blood substance concentration measurement method.

19. In the light irradiation step, the laser light is focused on the measurement target portion using a second lens positioned between the light irradiation unit and the measurement target portion. The method for measuring the concentration of a substance in blood according to claim 18.

20. In the step of forming an image of the reflected light on the photodetector, the reflected light is propagated through space in a section from the object placement unit to the photodetector in the optical path from the measurement object portion to the photodetector, except for a section passing through the first lens; In the light irradiation step, the laser light is propagated in a space in a section from the light irradiation unit to the object placement unit in the optical path from the light irradiation unit to the measurement object portion, except for a section passing through the second lens. The method for measuring the concentration of a substance in blood according to claim 19.

21. In the light irradiation step, laser light is irradiated onto the measurement target portion from a rear side of the living body placement surface of the target placement unit, In the step of forming an image on the photodetector, reflected light from the measurement target portion of the irradiated laser light is received on the back side of the target placement unit. The method for measuring the concentration of a substance in blood according to claim 20.

22. prior to imaging the reflected light onto a photodetector; adjusting the optical path length from the measurement target portion to the photodetector so that the reflected light from the measurement target portion forms an image on the photodetector; A method for measuring the concentration of a substance in blood according to any one of claims 18 to 21.

23. The step of adjusting the optical path length is carried out by receiving the reflected light reflected from the measurement target portion using a two-dimensional imaging means that is positioned in a positional relationship with respect to the measurement target portion equivalent to that of the photodetector, and detecting whether an image based on the reflected light is formed. The method for measuring the concentration of a substance in blood according to claim 22.

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