Substance-in-blood concentration measurement method

Abstract

To stably perform measurement with high accuracy regardless of variations in a condition of a measurement target or an irradiation condition of a laser beam.SOLUTION: A substance-in-blood concentration measurement device 1 for measuring concentration of a substance in blood of a living body Ob, includes: a target placement unit 10 on which the living body Ob that includes a measurement target portion Mp is placed; a light emission unit 20 that irradiates the measurement target portion Mp with a laser beam L1; a photodetector 30 that receives reflected light L2 of the laser beam reflected from the measurement target portion Mp and detects intensity of the reflected light; and a condenser lens 40 disposed between the measurement target portion Mp and the photodetector 30. On an optical path Op2 from the measurement target portion Mp to the photodetector 30, the laser beam L2 propagates through a space, except where transmitted through the condenser lens 40, and the condenser lens 40 forms an image of the reflected light L2 reflected from the measurement target portion Mp on the photodetector 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 check the state of blood substances such as blood glucose levels and blood lipid levels. In particular, for patients with diabetes, which is 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 an invasive method of taking blood samples from patients and performing chemical analysis of the blood has been used until now.

[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 simply by irradiating a living body with high-intensity mid-infrared light through a waveguide and guiding the reflected light to a photodetector through 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 a problem in 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 measuring device and a blood substance concentration measuring method that are capable of stably performing highly accurate measurements regardless of fluctuations in the state of the measurement subject or the laser light irradiation conditions. [Means for solving the problem]

[0007] In order to achieve the above-mentioned 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 a subject 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 subject placement section to the photodetector in the optical path from the measurement target portion to the photodetector, the reflected light propagates in 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. Effect of the Invention

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

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

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

[0011] As shown in Fig. 17, the device 1X includes an object placement section 10X on which a living body Ob to be examined is placed, a light irradiation section 20X for irradiating a pulsed laser light L1 made of mid-infrared light, a light guide section 90X in which an entrance side waveguide 91X and an exit side waveguide 92X made of through holes are opened, a photodetector 30X for receiving reflected light LX2 from the living body Ob and detecting its intensity, and a control section 60X for these. Patent Document 1 describes that the device 1X can measure blood glucose concentration non-invasively and with a simple configuration by irradiating high-intensity mid-infrared light.

[0012] However, as described above, the inventors' experiments 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 or slight changes in the conditions of the irradiated laser light, making it difficult to perform stable, normal measurements.

[0013] According to the inventors' study, the reason for the measurement value fluctuation is that the light component reflected from the skin surface and the light component reflected from the inside of the body below the skin surface, which contains the blood glucose that is the original measurement target, are not separated, and the two components are mixed and detected by the photodetector. To solve this, for example, it is necessary to set the optical system for each subject and each measurement so that it matches the subject's biological conditions and measurement conditions. However, it requires high skill to appropriately adjust the optical system for each living body and each measurement, and performing this in blood glucose measurement that patients themselves perform daily will greatly impair the convenience of the non-invasive method.

[0014] Therefore, the inventors conducted extensive research into the configuration of an optical system that can stably achieve highly accurate measurements in a non-invasive blood substance concentration measurement method, regardless of fluctuations in the state of the measurement subject or the laser light irradiation conditions, and arrived at the following embodiment.

[0015] <<Overview of the embodiment of 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 a subject 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 subject 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] With this configuration, compared to conventional devices using a waveguide, it is possible to reduce false signal (noise) components caused by reflected light scattered on the skin surface, improving the S / N ratio in optical measurement. This makes it possible to always perform highly accurate optical measurement regardless of the condition of the skin surface, which varies from subject to subject and from measurement to measurement. This makes it possible to provide a blood substance concentration measuring device that can stably perform highly accurate measurements regardless of the condition of the measurement target or the variation in the laser light irradiation conditions. As a result, it is possible to realize a non-invasive and simple measurement method for blood glucose level measurement, which is performed daily by patients themselves, without 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 laser light onto the measurement target portion from the back side of the living body placement surface of the subject placement unit, and the light detector 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 is a portion of the living body located inward from 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 main part to be measured, are imaged on the screen of the photodetector and reflected in the optical measurement by the photodetector, thereby making it possible to perform measurements 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, the second lens focusing the laser light on the measurement target portion, and the laser light may be configured to propagate through space 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, except for the section passing through the second lens.

[0022] With this configuration, the laser light emitted from the light irradiating unit can be focused at a depth corresponding to a part of the living body located inside the epidermis, which is a measurement target part located a predetermined distance from the surface of the target placement unit. At this time, the irradiation range of the laser light can be reduced to a size corresponding to the measurement target part.

[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 an image forming position of the reflected light 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 inward from 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 changed to change 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, making it 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 regular 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 mounting portion on which the living body is placed, and the angle of emission of the optical 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 receiving optical system and the emitting optical system can be constructed to a certain extent.

[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 the measurement of blood glucose concentration, which is more highly absorbed by glucose than the near-infrared light conventionally used. Also, since the transmittance into the body is lower than that of the near-infrared light conventionally used to measure blood glucose levels, only the epidermis is observed, and the effect is that it is 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 measurement device.

[0036] 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 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, it is possible to observe only the epidermis, and the 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 which outputs the intensity of the reflected light as a one-dimensional value, and may be configured to be arranged 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 which receives the reflected light reflected from the measurement target portion and detects whether an image based on the reflected light has been formed.

[0041] With this configuration, the process of adjusting the optical path length from the measurement target portion to the photodetector in order to form an image of 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 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 on the photodetector.

[0044] In another aspect, in any of the above aspects, the subject placement portion may have a through hole opened in an area where the surface of the living body is abutted, 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 further, the laser light irradiated from the light irradiating unit can be directly irradiated onto the surface of the living body Ob, 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 an 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] With this configuration, total reflection on the surface of the living body can be suppressed, 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 the optical systems such as the light irradiation section are located, thereby providing the target placement section with a dustproof function.

[0048] Furthermore, a blood substance concentration measuring method according to an embodiment of the present disclosure may be a blood substance concentration measuring 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 imaging reflected light reflected from the measurement target portion on the light detector using a first lens located between the measurement target portion and a light detector on the back side of the subject placement unit, and a light detection step of receiving the reflected light with the light detector and detecting the intensity of the reflected light.

[0049] With this configuration, highly accurate measurements can be stably performed 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 process 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 section can be focused at a depth corresponding to a measurement target portion of a living body that is spaced a predetermined distance from the surface of the subject placement section.

[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 portion to the photodetector in the optical path from the portion to be measured to the photodetector, except for a section that passes through the first lens; and in the light irradiation step, the laser light is propagated in space in a section from the light irradiation portion to the object placement portion in the optical path from the light irradiation portion to the portion to be measured, 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 section, 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 section.

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

[0055] In another aspect, in any of the above aspects, prior to the step of forming an image of the reflected light on a photodetector, a step of adjusting the optical path length from the portion to be measured to the photodetector may be included so that the reflected light reflected from the portion to be measured is formed on the photodetector.

[0056] With this configuration, it is possible to form an image of the reflected light from the measurement target portion on the photodetector.

[0057] In another aspect, in any of the above aspects, the step of adjusting the optical path length may be performed by having a two-dimensional imaging means arranged in a relative positional relationship with respect to the measurement portion equivalent to that of the photodetector receive reflected light from the measurement portion, and detecting whether or not 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 form an image of 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 The 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" surface and the surface facing the negative height direction may be referred to as the "back" surface. Also, the scale of the components in each drawing is not necessarily the same as the actual scale. In this specification, the symbol "~" used to indicate a numerical range includes both ends of the range. The materials, numerical values, etc. described in this embodiment are merely examples of preferred ones, and are not limited thereto.

[0060] <Overall composition> The blood substance concentration measuring device 1 (hereinafter, sometimes referred to as "device 1") is a medical device that non-invasively measures the blood substance concentration of a living body at a measurement target part by irradiating a laser light of a specific wavelength from a light source to the measurement target part of the living body and detecting the intensity of the reflected light from the measurement target part. The laser light is light of a specific wavelength that can be absorbed by the substance to be measured. When the blood substance concentration is high, the intensity of the reflected light from the measurement target part decreases due to absorption by the substance, so the device 1 measures the blood substance concentration 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, and may be a predetermined wavelength selected from the range of 2.5 μm to 12 μm. More preferably, it may be a predetermined wavelength selected from the range of 6.0 μm to 12 μm. Specifically, for example, it may be 9.26±0.05 μm (9.21 μm to 9.31 μm). Alternatively, 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, 9.57 μm, 9.77 μm, 10.04 μm, or 10.92 μm. This allows the glucose concentration in the epithelial interstitial fluid to be measured as the blood glucose level. In this case, it is necessary to measure the glucose concentration in the interstitial fluid just below the skin, and it is preferable to use mid-infrared light, which has high absorption and does not penetrate deep into the body. In addition, by using mid-infrared light, the influence of overtones and combination tones is small, and glucose can be measured more accurately than with near-infrared light.

[0061] Fig. 1 is a schematic diagram showing a configuration of an apparatus 1 according to embodiment 1. As shown in Fig. 1, the apparatus 1 has an object placement unit 10, a light irradiation unit 20, a light detector 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 section 10 is a plate-like guide member for restricting the measurement target portion Mp of the subject Ob to a specified position and angle suitable for measurement by abutting the surface of the skin of the subject Ob against its surface 10a. In this case, the surface 10a of the subject placement section 10 becomes the subject placement surface. By covering the optical system of the subject placement section 10, such as the light irradiation section 20, with a housing (not shown) and providing the subject placement section 10 on the outer periphery of the housing, the subject placement section 10 can function as an irradiation window through which the laser light L1 is irradiated from the inside.

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

[0065] The object placement section 10 is arranged so that the laser light L1 irradiated from the light irradiating section 20 enters from the back surface 10d side, and the relative angle with the light irradiating section 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 based on the normal to the front surface 10a of the object placement section 10 on which the living body Ob is placed.

[0066] 2(a) and (b) are enlarged cross-sectional views showing the aspect of part A in FIG. 1. The enlarged views show the part where the measurement target part Mp of the living body Ob is abutted against the object placement part 10. As shown in FIG. 2(a), the surface 10a of the object placement part 10 may be formed with a recessed part 10b so that a gap is formed between the surface 10a and the living body Ob. In this case, the laser light L1 irradiated from the light irradiating part 20 passes through the bottom part of the recessed part 10b in the object placement part 10 and is irradiated to the surface of the living body Ob. Since the object placement part 10 does not have an opening, it is possible to prevent dust, dirt, water vapor, etc. from entering the atmosphere in which the optical system such as the light irradiating part 20 exists, and the object placement part 10 can have a dustproof function.

[0067] By providing the recess 10b, an air layer is formed between the surface 10a of the target placement part 10 and the living body Ob, and total reflection on the surface of the living body Ob can be suppressed compared to the case where the living body Ob is in contact with the target placement part 10. Furthermore, by providing the recess 10b, the living body Ob can be more easily attached to the surface 10a of the target placement part 10 in the area other than the recess 10b. In this embodiment, as an example, the thickness of the target placement part 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 about 400 μm.

[0068] 2(b), an opening 10c may be formed in a region of the surface 10a of the target placement part 10 that contacts the surface of the living body Ob. The opening 10c allows the laser light L1 irradiated from the light irradiating part 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 part 10.

[0069] By providing the opening 10c, an air layer can be formed in the portion where the surface 10a of the object placement part 10 contacts the living body Ob, and total reflection on the surface of the living body Ob can be suppressed compared to the case where the living body Ob is in contact with the object placement part 10. Furthermore, by providing the opening 10c, a configuration can be achieved in which the living body Ob can be more easily attached to the surface 10a of the object placement part 10 around the opening 10c of the surface 10a. In this embodiment, as an example, the thickness of the object placement part 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 a 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 disposed 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 irradiation unit 20 in the blood substance concentration measuring device 1. As shown in FIG. 3, the light irradiation unit 20 has a light source 21 that oscillates pump light L0 with a wavelength shorter than the pulsed mid-infrared light, and an optical parametric oscillator (OPO) 22 that converts the pump light L0 to a longer wavelength, amplifies it, and outputs it as laser light L1. In the optical parametric oscillator 22, the pump light L0 is incident on a nonlinear optical crystal contained therein, so that light of two different wavelengths is oscillated, and a short-wavelength signal light and a long-wavelength idler light are generated. In the light irradiation unit 20, the idler light is output to the subsequent stage as the laser light L1 and used for measuring the blood glucose level. The optical parametric oscillator 22 may have a configuration described in a known document, for example, JP 2010-281891 A. Here, mid-infrared light is used as the wavelength oscillated by optical parametric oscillation, which is a wavelength that is more highly absorbed by glucose than the near-infrared light conventionally used, and is set to 9.26 μm in this embodiment. Since this mid-infrared light has a lower transmittance into the body than the near-infrared light conventionally used to measure blood glucose levels, only the epidermis is observed, and the effect is that it is less susceptible to the influence of other biological components present deep inside. In addition, the effect is that the overlap of harmonics and combination tones of the normal vibration has less adverse effects on the measurement.

[0072] The light source 21 may include 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 the pump light L0, which has a wavelength shorter than mid-infrared light, to be oscillated in a pulsed form. The pump light L0 may have a pulse width of about 8 ns and a frequency of 10 Hz or more, for example. Furthermore, the 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, so the light source 21 can be simplified and made compact.

[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, and 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. The light L01 transmitted through the incident side semi-mirror 221 enters the nonlinear optical crystal 223 and is converted to light of 9.26 μm, which is a wavelength 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] In the nonlinear optical crystal 223, AgGaS suitable for wavelength conversion is used under phase matching conditions. The wavelength of the oscillated laser light L1 can be adjusted by adjusting the type and matching conditions of the nonlinear optical crystal 223. GaSe, ZnGeP2, CdSiP2, LiInS2, LiGaSe2, LiInSe2, LiGaTe2, etc. may 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 irradiation unit 20 uses the light source 21 and the optical parametric oscillator 22, and thus can achieve a wavelength of 10 times faster than 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 as that of the conventional laser light source.

[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 in the optical path Op1 of the laser light L1 from the light irradiating unit 20 to the measurement target portion Mp to condense the irradiated light on the measurement target portion Mp of the living body Ob. In the section from the light irradiating unit 20 to the back surface 10d of the object placement portion 10a in the optical path Op1, the laser light L1 is configured to propagate in a space such as a 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 irradiating unit 20 is condensed at a depth corresponding to the measurement target portion Mp of the living body Ob, which is located a predetermined distance away from the surface 10a of the object placement portion 10, for example, a biological part located inward from the epidermis such as the dermis. The incident angle θ of the laser light L1 onto the measurement target portion Mp is determined by the angle of the light irradiating unit 20 with respect to the surface 10a of the target mounting portion 10 and the refraction angle of the laser light L1 incident onto the target mounting portion 10. In this embodiment, the incident angle θ may be, for example, 45 degrees or more, and 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 part 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 and to use this for normalization processing of the detection signal in the photodetector 30. The output of the photodetector 30 can be compensated based on the fluctuation 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 and is scattered or diffusely reflected as reflected light L2, which passes through the object placement section 10 again and 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 part 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 part Mp of the living body Ob to the photodetector 30 to image the reflected light L2 diffusely reflected at the measurement target part 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 part 10 to the photodetector 40, the reflected light L2 is configured to propagate through a space such as a 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 imaged Im2 on the screen 30a of the photodetector 30 by the imaging lens 40 as reflected light L2.

[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 equivalent lengths, and a positional relationship is established in which an image Im1 at a depth corresponding to a portion of the living body located inside the epidermis such as the dermis (hereinafter sometimes referred to as an "inner portion of the living body") that corresponds to the measurement target portion Mp of the living body Ob irradiated with mid-infrared light 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 the above, and the magnifications of distances Op21 and Op22 may be set so that the image Im1 of the target mounting 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 to the imaging lens 40 is determined by the angle of the imaging lens 40 with respect to the surface 10a of the target mounting portion 10 and the refraction angle of the reflected light L2 emitted from the target mounting portion 10. In this embodiment, the incident angle may be, for example, from 0 degrees to 40 degrees, and more preferably from 20 degrees to 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 mounting surface 10a of the subject mounting unit 10, and is configured to receive reflected light from the measurement target portion Mp of the living body Ob on the living body mounting surface (front surface 10a) from the back surface 10d side of the subject mounting unit 10. The photodetector 30 outputs an electrical signal according 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 irradiating unit 20 increases the intensity of the irradiated laser light L1, and the imaging lens 40 forms an image of the reflected light reflected from the measurement target portion Mp on the photodetector 30, so that the photodetector 30 can receive reflected light with a sufficiently high intensity compared to the background light, achieving a high S / N ratio and enabling highly accurate measurement. As described above, since the laser light L1 and the reflected light L2 are monochromatic and of high intensity, the only processing required for the photodetector 30 is the detection of the light intensity, and there is no need to perform spectrum analysis based on wavelength sweeping or multivariate analysis as in the photoacoustic optical method using a quantum cascade laser. Therefore, the accuracy required for detection is relaxed, and a simple electronic cooling method or the like can be used.

[0087] For example, a HgCdTe infrared detector cooled with liquid nitrogen may be used as the photodetector 30. In this case, by cooling the detector to about 77 K with liquid nitrogen, the light 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, and 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 the fluctuation 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 Related to Blood Substance Concentration Measuring Device 1) [Test equipment and conditions] As an example, a 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 part 10 was set horizontally, and a mid-infrared laser beam was emitted upward from the light irradiation part 20 at a launch angle of 24.5 degrees, and irradiated onto a measurement position marked from the bottom of the object placement part 10. At this time, the irradiation range of the laser beam L1 was reduced by the condenser lens 50 to a size according to the measurement position.

[0093] (2) The subject's fingertip was placed on the upper surface 10a of the subject placement section 10, and the incidence 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 under the object placement unit 10, and imaged 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 2F, and a positional relationship was set such that an image Im1 of a depth corresponding to the part of the living body located inward from the epidermis, which corresponds to the measurement target portion Mp, is transferred to the photodetector 30 with an equivalent size.

[0095] (4) The angle of the optical path Op2 between the photodetector 30 and the imaging lens 40 was set to be inclined by 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 0 min, the measurement start time), placed the subject's fingertip on the upper surface 10a of the subject placement unit 10, and continuously performed optical measurements according to the embodiment 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 intensity of the mid-infrared light when it was irradiated onto the human body.

[0098] (2) In parallel with the optical measurements, blood glucose levels were measured by subjects taking their own blood samples (SMBG: Self Monitoring of Blood Glucose).

[0099] (3) Optical measurement and blood glucose measurement by self-drawing 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 diagrams comparing, over time, the change in the glucose concentration measured by the photodetector of conventional device 1X and the change in the glucose concentration measured by an invasive measuring device according to a comparative example. Figures 6(a) to (d) are diagrams 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 (d) show the results of tests conducted on the same subject on different test days.

[0103] After ingestion of 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) 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 measured 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 and the response was extremely small (Figure 6(d)).

[0106] In this way, with the conventional device 1X according to the comparative example, normal measurement was not possible depending on the test day even under the same conditions.

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

[0108] Figures 7(a) to (c) are diagrams 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. 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 an invasive blood glucose concentration measuring device in Figures 7(a) to (c).

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

[0110] As shown in Figures 7(a) to (c), the detected light intensity from the measurements decreases and then increases over time after the 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(b), and negative correlations were 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 performed on different test days.

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

[0113] 9 is a schematic diagram of an experimental apparatus for measuring glucose concentration values ​​measured by a photodetector by changing the angle and optical path length of the optical path on the light receiving side in a blood substance concentration measuring device 1. Using the blood substance concentration measuring device 1 of the embodiment in Test 1, optical measurement was 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 based on the normal to the surface of the subject mounting unit 10 on which the living body Ob is placed (vertical direction in FIG. 9). 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 Fig. 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 variability in the measurement results for each measurement at each angle φ.

[0115] From FIG. 10(a), absorption was observed when the angle φ was between 0 degrees and 40 degrees, and the largest absorption was observed when the angle was between 20 degrees 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 regular reflection of the incident light, and it is considered to be unsuitable for use in optical measurement. Furthermore, since an input / output ratio value of 0.2 or less is preferable from the viewpoint of measurement accuracy, it is even more preferable that the angle φ is 30 degrees or less, and since an input / output ratio value of less than 0.1 is not preferable from the viewpoint of the S / N ratio of the measurement signal, it is even more preferable that the angle φ is 20 degrees or more.

[0116] In addition, as shown in Fig. 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] In addition, when the angle φ is 45 degrees or more, measurement is difficult due to the device configuration. When the angle φ is in the range of less than 20 degrees, the light receiving optical system and the light emitting optical system are close to each other, which makes the layout of the optical system of the blood substance concentration measuring device 1 difficult.

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

[0119] (Test 3: Evaluation test with different 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] with respect 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 change in glucose concentration measured by a photodetector when the length of the light path on the light receiving side in the blood substance concentration measuring device 1 is changed, and the change in glucose concentration measured by an invasive measuring device.

[0122] 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 2F [mm], as described above, the detected light intensity from the measurement, as shown in Figure 7(a), 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 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 did not show a tendency to decrease and then increase over time after ingestion of the aqueous solution due to light absorption accompanying an increase in blood glucose concentration, as shown in Figure 11 (a) and (b). In Figure 11 (a), the reaction due to the change in blood glucose level was extremely small, and in Figure 11 (b), the reaction due to the change in blood glucose level was almost nonexistent. In addition, the correlation with the blood glucose level measurement results by SMBG was low (Figures 12 (a) and (b)).

[0125] From the above results, it is considered preferable that the light receiving side optical path length L, 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 part 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 the reflected light from the measurement target part 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. At this time, the distance between the upper surface 10a of the target placement part 10, which corresponds to the skin surface, and the center of the imaging lens 40 is about 50 mm, which is about 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 the optical measurement by the blood substance concentration measuring device 1 according to the embodiment provides measurement results that are highly correlated with the blood glucose level measurement results by SMBG and highly reproducible, compared to the conventional device 1X according to the comparative example. The blood substance concentration measuring device 1 employs an optical system having an imaging lens 40 between the measurement target portion Mp and the photodetector 30, and an image of the reflected light L2 reflected from the measurement target portion Mp on the photodetector 30, which is thought to have enabled highly reproducible optical measurement.

[0128] The reason for this is that in the conventional device 1X using the waveguide of the comparative example, it was not possible 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 in the blood substance concentration measuring device 1 of the embodiment, the signal from under the skin is collected on the optical sensor, so the impact of slight changes in the measurement conditions on the measurement results is reduced, and it is believed 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 an optical path from a light irradiator 20X to a 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, the 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 part Mp of the living body Ob. At this time, in addition to the reflected light component (Im11) from the inside part of the living body below the skin surface to be measured that can be absorbed by blood glucose, a reflected light component (Im12) from the skin surface is generated. In the conventional device 1X using a waveguide, these reflected light components (Im11, Im12) enter the exit side waveguide 92X and are configured to be guided to the screen 30Xa of the photodetector 30.

[0131] That is, in the conventional device 1X, the reflected light component (Im12) from the skin surface and the reflected light component (Im11) from the inside of the living body below the skin surface are not separated, and the two components are mixed and detected by the photodetector. As a result, the measurement result includes the reflected light component (Im12) other than the reflected light component (Im11) from the inside 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 irradiating unit 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 irradiating unit 20 enters the living body Ob at an incident angle θ along an optical path toward the test target part Mp of the living body Ob, and in addition to the light component (Im11) absorbed by blood glucose and reflected from the inside of the living body below the skin surface to be the measurement target part Mp, a light component (Im12) reflected from the skin surface is generated.

[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 since 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 reflected light component is guided outside the range of the screen 30a of the photodetector 30, or even if it is guided within the range of the screen 30a of the photodetector 30, it is not imaged (is blurred), and therefore the amount of light decreases and the signal intensity detected by the photodetector 30 decreases. As a result, the reflected light component (Im12) from the skin surface, which is detected as noise, has a small influence on the optical measurement.

[0134] In other words, with the blood substance concentration measuring device 1, the reflected light component (Im11) from the inner part of the body below the skin surface, 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, so it is thought that the measurement results are more highly correlated with the blood glucose level measurement results by SMBG and more reproducible than the comparative example.

[0135] Thus, in the blood substance concentration measuring device 1, compared to the conventional device 1X using a waveguide, it is possible to reduce false signal (noise) components caused by reflected light scattered on the skin surface, and improve the S / N ratio in optical measurement. This also makes it possible to always perform highly accurate optical measurement regardless of the state of the skin surface, which varies from test subject to test subject, or from measurement to measurement. Furthermore, by adjusting the position of the photodetector, it is possible to obtain the effect of being able to accommodate measurement subjects with thick skin by changing the optical path length L on the light receiving side.

[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 body Ob, and includes a subject placement section 10 on which a measurement target portion Mp of the living body 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 body placement surface (front surface 10a) of the subject placement section 10, and a light irradiating section 20 that irradiates the measurement target portion Mp with laser light L1 from the back surface 10d side of the subject placement section 10. 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 in space except for the section passing 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 allows for stable and highly accurate measurement regardless of the state of the measurement target or the fluctuations in the laser light irradiation conditions. As a result, it is possible to realize a non-invasive and simple measurement method that eliminates the need to appropriately adjust the optical system for each living body or each time a measurement is performed, in blood glucose level measurements that are performed daily by patients themselves.

[0138] Second Embodiment The blood substance concentration measuring device 1 of embodiment 1 comprises a subject mounting section 10, a light irradiation section 20, a photodetector 30, and an imaging lens 40, and is configured so 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 form an image of the reflected light L2 reflected from the measurement target portion Mp on the photodetector 30 is not limited to these, and may be another embodiment.

[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 will not be described.

[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 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) has been 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 the light detector 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. When the two-dimensional imaging means 71A is positioned on the optical path L2, 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 light detector 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 the 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 respect to the measurement target portion Mp.

[0146] Next, in this state, the two-dimensional imaging means 71A is caused to receive the reflected light reflected from the measurement target portion Mp, and it is detected whether or not an image based on the reflected light has been formed. If an image has not been formed, the position of the two-dimensional imaging means 71A on the optical path L2 is gradually moved, and the detection of whether or not an image has been 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 marked with a scale in 0.5 mm increments on the object placement section 10 as shown in FIG. 15, acquiring an image with the two-dimensional imaging means 71A, and detecting the focus position within the image. At this time, for example, the focus position may be the maximum point of the luminance 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 match, 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 match on the optical path L2, and it is determined whether an image is formed or not.

[0149] Then, 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 of embodiment 2 is configured to be configurable 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) has been 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 configure 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 section 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 section 20 may be varied depending on the type of blood component to be detected.

[0154] Hereinafter, a blood substance concentration measuring device according to the third embodiment will be described with reference to the drawings. In the blood substance concentration measuring device according to the third embodiment, the wavelength of the laser light L1 emitted by the light irradiating unit 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 5.77 μm, 6.87 μm, 7.27 μm, 8.87 μm, or 9.55 μm, and may be in the range of -0.05 μm or more and +0.05 μm or less.

[0155] 16 is a diagram showing changes in the lactate concentration measured by the photodetector when the wavelength of light emitted by the 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 by optical measurement roughly correlates with the lactate level measurement result (comparison value) 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 that has a different phase matching condition of the nonlinear crystal 223.

[0157] Furthermore, in the light irradiation unit 20, a device configuration may be adopted in which a plurality of optical parametric oscillators 22 can be selectively used to selectively irradiate laser light L1 of a plurality of wavelengths, thereby making it possible to make the device capable of measuring a plurality of 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 light guided, and can share an optical system consisting of a focusing lens 50, a subject mounting portion 10, an imaging lens 40, and a photodetector 30 capable of detecting mid-infrared light with a measuring device for other blood components such as glucose.

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

[0160] <<Variations>> Although 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. For example, the present disclosure also includes forms obtained by applying 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 having 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 may be changed as appropriate to another aspect as the light receiving optical system. For example, a configuration using multiple lenses or a configuration in which a mirror is disposed in the middle of the optical path may be used.

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

[0163] (3) In the above embodiment, the photodetector 30 is an infrared sensor composed of a single light receiving element capable of detecting mid-infrared light. However, the photodetector 30 may be 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 the light receiving surface. 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 in order to form an image of the reflected light from the measurement target portion Mp on the photodetector 30. Specifically, in the optical path length adjustment step, the photodetector 30 is made to receive the reflected light reflected from the measurement target portion Mp, and it is detected whether an image based on the reflected light is formed or not. If an image is not formed, the position of the photodetector 30 on the optical path L2 is gradually moved, and the detection of whether an image is formed or not is repeated. This makes it possible to perform the step of adjusting the optical path length from the measurement target portion Mp to the photodetector 30 using the photodetector 30 itself, 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 laser light L1 to the measurement target portion Mp from the back surface 10d of the living body placement surface (front surface 10a) of the subject placement unit 10, and the photodetector 30 is configured to receive 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 section 20 may be configured to irradiate the laser light L1 to the measurement target portion Mp from the surface 10a side of the living body placement surface (surface 10a) of the subject placement section 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 subject placement section 10.

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

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

[0168] With this configuration, the light irradiating section 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 section 10, thereby measuring the concentration of a substance in blood.

[0169] <Additional Information> The above-described embodiments each show a preferred specific example of the present invention. The numerical values, shapes, materials, components, the arrangement and connection of the components, steps, and the order of steps shown in the embodiments are merely examples and are not intended to limit the present invention. Furthermore, among the components in the embodiments, those that are not described in the independent claims showing the highest concept of the present invention are described as optional components constituting a more preferred embodiment.

[0170] In addition, the order in which the above-mentioned methods are performed is merely for illustrative purposes, and orders other than those described above may be used. In addition, some of the above-mentioned 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 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 without departing from the gist of the present invention.

[0172] Furthermore, at least some of the functions of each of the embodiments and their modified examples 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, blood lipid levels, etc. 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, comprising: 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 an optical path of the reflected light; the reflected light propagates in a space in a section from the object placement part to the photodetector in the optical path from the measurement object part 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 reflected light from the measurement target portion of the laser light irradiated on the back side of the target placement portion. 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 irradiation area of ​​the laser light on the measurement target onto a light receiving surface of a detector.

3. The blood substance concentration measuring device according to claim 1 or 2.

4. a second lens that is located between the light irradiation unit and the measurement target portion in the optical path of the laser light and focuses the laser light on the measurement target portion; In a section from the light irradiation unit to the object placement unit in an optical path from the light irradiation unit to the measurement object portion, the laser light propagates in a 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 image forming position of the reflected light on the skin surface.

5. The blood substance concentration measuring device according to claim 1.

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 angle of incidence of the laser light on the measurement target portion is different from the angle of emergence of the light path from the measurement target portion to the light detector.

7. The blood substance concentration measuring device according to claim 1.

8. The emission angle of the optical path from the measurement target portion to the photodetector is 0 degrees or more and 90 degrees or less with respect to a normal line to a surface on which the living body is placed in the target placement unit, and is different from the incidence angle of the laser light to the measurement target portion with respect to the normal line. 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 placed; The emission angle of the optical path from the measurement target portion to the optical detector 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 arranged so that a relative positional relationship with respect to the measurement target portion is equivalent to that of the photodetector, receiving light reflected from the measurement target portion and detecting 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 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.

16. An apparatus for measuring the concentration of a substance in blood according to claim 1.

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 subject placement section and irradiated onto the surface of the living body, The reflected light is transmitted through the object placement portion and received by the photodetector.

16. An apparatus for measuring the concentration of a substance in blood according to claim 1.

18. A method for measuring a 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 located 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 located 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 in a space in a section from the object placement part to the photodetector in an optical path from the measurement object part 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 an 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, a laser light is irradiated onto the measurement target portion from a rear side of the living body placement surface of the target placement portion, In the step of forming an image on the photodetector, reflected light of the irradiated laser light from the measurement target portion is received on the back side of the target placement portion. 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 a 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 performed by receiving light reflected from the measurement target portion using a two-dimensional imaging means that is disposed in a positional relationship equivalent to that of the photodetector relative to the measurement target portion, 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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