In-blood substance concentration measurement device, in-blood substance concentration measurement method, and program

Abstract

The present invention comprises: a light irradiation unit 20 that focuses laser light on a specific region of a subject part Mp0 in the skin of a living body OB on the opposite side to the side of the skin surface of the living body facing a main surface 10a of a base 10; a light detector 30 that, on the main surface side of the base, receives signal light, in which the intensity of light of some wavelengths has been decreased from that of the laser light, and that detects the intensity of the signal light; a lens 40 that is disposed at a position at which it is possible to form, on the light detector, an image of the signal light emitted from a laser light focus region FA; and a measurement control unit 60 that measures the concentration of an in-blood substance on the basis of the intensity of the signal light. The angle A formed by the normal of the skin surface of the subject part and the optical path of laser light L1 differs from the angle B formed by the normal and the optical path of signal light L2 from the laser light focus region to the light detector. An image of signal light emitted from a blood vessel region Mp which overlaps with the laser light focus region is formed on a light-receiving surface of the light detector by the lens.

Description

Blood substance concentration measuring device, blood substance concentration measuring method, and program

[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.

[0002] In the prevention and treatment of lifestyle-related diseases, it is important to routinely monitor blood glucose levels, blood lipid levels, etc. In particular, patients with diabetes, one of the lifestyle-related diseases, are required to measure the glucose concentration in their blood and manage their blood glucose levels on a daily basis to prevent complications. This has traditionally been achieved by invasive methods, in which blood samples are taken from patients and chemical analysis is performed.

[0003] In response to this, simple non-invasive methods have been proposed in recent years for optically analyzing the state of blood in the body without blood sampling (for example, Patent Documents 1 and 2).

[0004] International Publication No. 2016 / 117520 Japanese Patent Application Laid-Open No. 2009-168670

[0005] However, in the blood substance concentration measuring devices described in Patent Documents 1 and 2, measurements are performed by bringing the measured area into contact with a light irradiation window provided on the outer surface of the measuring device. Therefore, depending on how the measured area is placed on the light irradiation window, the pressure applied to the measured area and the measurement position may change, resulting in changes in the measurement results, making it difficult to obtain stable and sufficient measurement accuracy.

[0006] The present disclosure has been made in consideration of the above-mentioned problems, and aims to provide a blood substance concentration measurement device, a blood substance concentration measurement method, and a program that can suppress changes in measurement results due to differences in how the measurement site is placed on the device, and can stably perform highly accurate measurements.

[0007] In order to achieve the above object, a blood substance concentration measuring device according to one aspect of the present disclosure is a blood substance concentration measuring device for measuring the concentration of a blood substance contained in the blood of a subject part of a living organism, comprising: a base on a main surface of which the living organism can be placed; a light irradiating unit that irradiates, from the main surface side of the base, laser light by concentrating it onto a specific region in the subject part that is located on the skin surface of the living organism on the side facing the main surface and in the skin located on the opposite side of the living organism; a photodetector on the main surface side of the base that receives signal light that is reflected light based on the laser light and in which the intensity of light of some wavelengths from the laser light is weakened, and detects the intensity of the signal light; and a light detector that is located between the subject part and the photodetector and that is capable of forming an image of the signal light emitted from the laser light concentration region in the subject part on the photodetector. and a measurement control unit that measures the concentration of the blood substance in the laser light focusing area based on the intensity of the signal light, wherein a first angle formed between a normal to the skin surface of the subject and the optical path of the laser light is different from a second angle formed between the normal and the optical path of the signal light from the laser light focusing area to the photodetector, the position of the living body relative to the light irradiating unit is defined so that a blood vessel area located inside the epidermis in the subject and the laser light focusing area overlap, and the position of the photodetector relative to the living body is defined so that an image of the signal light emitted from the blood vessel area Mp that overlaps with the laser light focusing area is transferred by the imaging lens and focused on the light receiving surface of the photodetector.

[0008] According to the blood substance concentration measuring device, blood substance concentration measuring method, and program of one aspect of the present disclosure, it is possible to suppress changes in measurement results due to differences in how the measurement site is placed on the device, and to perform highly accurate measurements stably.

[0009] 1 is a schematic diagram showing a state during measurement of the blood substance concentration measuring device 1 according to embodiment 1. FIG. 2 is a side view showing the configuration of the blood substance concentration measuring device 1. FIG. 3 is an enlarged view showing a part of the living body placed on the base in FIG. 2. FIG. 4 is a schematic diagram showing the configuration of the light irradiating unit 20 in the blood substance concentration measuring device 1. FIG. 5 is a diagram for explaining an overview of the light receiving side optical path in the blood substance concentration measuring device 1. FIG. 6 is a schematic diagram showing an overview of the optical path from the light irradiating unit 20 to the photodetector 30 in the blood substance concentration measuring device 1. FIG. 7 is a schematic diagram for explaining the operation of adjusting the optical path length from the laser light focusing area FA to the photodetector 30 by the blood substance concentration measuring device 1. FIG. 8 is a diagram showing the laser light irradiation position on the surface of a living body in measurement of a blood substance concentration by the blood substance concentration measuring device 1. FIG. 9 is a flowchart showing one aspect of the blood substance measurement operation by the blood substance concentration measuring device 1. FIG. 10 is a flowchart showing another aspect of the blood substance measurement operation by the blood substance concentration measuring device 1. FIG. 11 is a flowchart showing yet another aspect of the blood substance measurement operation by the blood substance concentration measuring device 1. 1 is a schematic diagram showing a state during measurement of a blood substance concentration measuring device 1A according to embodiment 2. FIG. 1 is a schematic diagram showing a state of an example of the blood substance concentration measuring device 1A. FIG. 14 is a schematic diagram showing a state during measurement of a blood substance concentration measuring device 1B according to embodiment 3, illustrating the results of a blood substance concentration measurement test using an example of the device 1A and a comparative example using SMBG.

[0010] Overview of Modes for Carrying Out the Invention A blood substance concentration measuring device according to an embodiment of the present disclosure is a blood substance concentration measuring device for measuring the concentration of a blood substance contained in the blood of a subject part of a living organism Ob, comprising: a base on a main surface of which the living organism can be placed; a light irradiation unit that irradiates, from the main surface side of the base, laser light by concentrating it onto a specific region in the subject part that is located on the skin surface of the living organism on the side facing the main surface and in the skin located on the opposite side of the living organism; a photodetector that, on the main surface side of the base, receives signal light that is reflected light based on the laser light and in which the intensity of light of some wavelengths from the laser light is weakened, and detects the intensity of the signal light; an imaging lens that is located between the subject part and the photodetector and at a position where an image of the signal light emitted from a laser light concentration region in the subject part can be formed on the photodetector; and a measurement control unit that measures the concentration of the blood substance in the laser light concentration region based on the intensity of the signal light, a first angle formed between a normal to the skin surface of the subject and the optical path of the laser light is different from a second angle formed between the normal and the optical path of the signal light from the laser light focusing area to the photodetector; the position of the living body relative to the light irradiation unit is defined so that a blood vessel area Mp located inside the epidermis in the subject and the laser light focusing area overlap; and the position of the photodetector relative to the living body is defined so that an image of the signal light emitted from the blood vessel area Mp that overlaps with the laser light focusing area is transferred by the imaging lens and focused on the light receiving surface of the photodetector.

[0011] With this configuration, laser light is focused and irradiated from the main surface of the base onto a specific area in the subject part located on the opposite side of the skin surface facing the main surface of the living body, and reflected light based on the laser light, i.e., signal light in which the intensity of light of some wavelengths from the laser light has been weakened, is received and measured on the main surface of the base, thereby preventing changes in the measurement results due to differences in how the part to be measured is placed on the device, and enabling stable, highly accurate measurements to be performed.

[0012] In another aspect, in any of the above aspects, the base may be configured to be able to adjust the position of the living body relative to the light irradiation unit by varying the height in the direction perpendicular to the main surface.

[0013] With this configuration, the positional relationship of the living body with respect to the light irradiation unit can be adjusted according to the shape of the individual living body so that the laser light is focused and irradiated onto the blood vessel region located inside the epidermis of the subject part. As a result, the position of the living body with respect to the light irradiation unit is regulated so that the blood vessel region located inside the epidermis of the subject part and the laser light focusing region overlap in the XZ plane.

[0014] In another aspect, in any of the above aspects, the position of the photodetector may be configured to be adjustable relative to the living body in a direction intersecting with the optical path of the signal light by changing the position of the photodetector in that direction.

[0015] With this configuration, the position of the photodetector can be adjusted so that the center of the photodetector screen and the position where the laser light is focused and irradiated onto the subject (laser light focusing area) roughly coincide with each other in a direction perpendicular to the optical path of the photodetector, or so that they partially overlap.

[0016] In another aspect, in any of the above aspects, the base may be configured to be able to simultaneously adjust the first angle and the second angle by varying the angle of the main surface with respect to the optical path of the laser light within a plane defined by the optical path of the laser light and the optical path from the subject area to the photodetector.

[0017] With this configuration, the incident angle and the installation angle with respect to the subject part can be simultaneously adjusted to match the shape of the individual living body.

[0018] In another aspect, in any of the above aspects, the position of the photodetector is configured to be adjustable relative to the living body in a direction along the optical path of the signal light by varying the position of the photodetector, and the position of the photodetector may be configured to be adjusted based on the concentration of the substance in the blood so that the image of the signal light emitted from the vascular region is transferred by the imaging lens and formed on the light receiving surface of the photodetector.

[0019] With this configuration, the position of the photodetector parallel to the optical path can be adjusted so that an image of a depth corresponding to the blood vessel region in the subject area is transferred to the screen of the photodetector as an image of equivalent size.

[0020] As a result, by using an imaging lens to focus the signal light emitted from the laser light focusing area on the screen of the photodetector, the photodetector can receive signal light with a sufficiently high intensity compared to the background light, achieving a high S / N ratio and enabling high-precision measurements.

[0021] In another aspect, in any of the above aspects, the light irradiating unit is configured to selectively irradiate a first laser light for subject measurement that is absorbed by a first blood substance, which is the substance to be measured, and a second laser light for reference measurement that is absorbed by a second blood substance, which is a reference substance, and the absorption rate of the second laser light by the second blood substance in the reference measurement may be greater than the absorption rate of the first laser light by the first blood substance in the subject measurement.

[0022] With this configuration, the first laser light is focused and emitted from the light emitting unit at the position of the detector where the signal light from the blood vessel is detected, and the signal light from the laser focused area is received by the detector, thereby making it possible to consistently and stably measure the concentration of the first blood substance with high accuracy regardless of individual differences in the position of the blood vessel in the depth direction from the skin surface of the subject. Therefore, it is possible to stably perform highly accurate measurements regardless of individual differences in the measurement subject.

[0023] In another aspect, in any of the above aspects, the reference substance may have a more stable concentration in blood than the measurement target substance.

[0024] With this configuration, the measurement accuracy of the measurement target can be improved by performing a reference measurement on a reference substance and then performing a target measurement.

[0025] In another aspect, in any of the above aspects, the measurement control unit may be configured to measure the concentration of the second blood substance when the specific region is included in a vascular region in the subject region based on the irradiation of the second laser light, and to be able to measure the concentration of the first blood substance in the specific region as the concentration of the first blood substance in the measurement target portion based on the irradiation of the first laser light.

[0026] With this configuration, the concentration of the first blood substance can be measured in a state where the laser focusing area is included in the blood vessel area in the subject part.

[0027] In another aspect, any of the above aspects may be configured to include a focusing lens located between the light irradiation unit and the subject part in the optical path of the laser light, which focuses the laser light onto the irradiation area.

[0028] This configuration can reduce the variation in the measurement results of the blood substance concentration for each measurement.

[0029] In another aspect, in any of the above aspects, in the section from the object placement section to the photodetector in the optical path from the object section to the photodetector, the signal light may propagate in space except for the section passing through the imaging lens, and in the section from the light irradiation section to the object placement section in the optical path from the light irradiation section to the object section, the laser light may propagate in space except for the section passing through the focusing lens.

[0030] With this configuration, compared to the conventional device described in Patent Document 1 that uses 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 measurements.

[0031] In another aspect, any of the above aspects may further include an imaging means for capturing an image including the living body, the measurement control unit may detect an image portion corresponding to the living body from the acquired image and calculate the amount of positional deviation of the image portion from a reference position where it should be, and the base may be configured to be able to change the height in the direction perpendicular to the main surface so as to compensate for the amount of positional deviation.

[0032] With this configuration, the position of the living body relative to the light irradiating unit can be easily adjusted to match the shape of the individual living body.

[0033] In another aspect, any of the above aspects may further include an imaging means for capturing an image including the living body, the measurement control unit may detect an image portion corresponding to the living body from the acquired image and calculate the amount of angular deviation from a reference angle at which the image portion should be, and the base may be configured to be able to change the angle of the main surface relative to the optical path of the laser light so as to compensate for the amount of angular deviation.

[0034] With this configuration, the incident angle and the installation angle with respect to the object part Mp0 can be simultaneously and easily adjusted to match the shape of an individual living body.

[0035] In another aspect, any of the above aspects may further include a light irradiation angle adjustment mechanism that holds the light irradiation unit and the photodetector and rotates to change the angles of the optical paths of the laser light and signal light relative to the skin surface of the living body within the laser light incident plane.

[0036] With this configuration, the angle of incidence of the laser light irradiated from the light irradiating unit onto the subject part and the installation angle of the photodetector relative to the subject part can be simultaneously adjusted, and the positions and angles of the photodetector and the light irradiating unit can be specified so that the optical paths of the laser light and the signal light intersect at a predetermined position.

[0037] In another aspect, any of the above aspects may further include a position adjustment mechanism that changes the position of the light irradiation angle adjustment mechanism within the laser light incident surface.

[0038] With this configuration, the intersection of the optical path of the laser light and the optical path of the signal light relative to the skin surface of the living body can be moved to the position that should be the test area of ​​the living body, allowing the subject to more easily measure the concentration of a substance in their blood without being concerned about how to place the test area on the device or the angle of incidence of the laser or the installation angle of the detector.

[0039] A blood substance concentration measurement method according to an embodiment of the present disclosure is a blood substance concentration measurement method for measuring the concentration of a blood substance contained in the blood of a subject part of a living organism, comprising: placing the living organism on a main surface of a base; and using a light irradiator to irradiate, from the main surface side of the base, a specific region of the subject part located on the skin surface of the living organism facing the main surface and in the skin located on the opposite side of the living organism, laser light for measuring the target substance, which is absorbed by the blood substance, by concentrating the laser light; using an imaging lens located between the subject part and a photodetector on the main surface side of the base, an image of signal light, which is reflected light of the laser light and emitted from a laser light concentration region in the subject part, with the intensity of light of some wavelengths of the laser light weakened, on the photodetector; receiving the signal light by the photodetector, and measuring the concentration of the blood substance in the specific region based on the intensity of the signal light; The configuration may be such that a first angle formed between a normal to the skin surface of the subject and the optical path of the laser light is different from a second angle formed between the normal and the optical path of the signal light from the specific region to the photodetector, the position of the living body relative to the light irradiation unit is defined so that a blood vessel region Mp located inside the epidermis in the subject and the laser light focusing region overlap, and the position of the photodetector relative to the living body is defined so that an image of the signal light emitted from the blood vessel region Mp that overlaps the laser light focusing region is transferred by the imaging lens and focused on the light receiving surface of the photodetector.

[0040] This configuration makes it possible to provide a method for measuring the concentration of a substance in blood that can suppress changes in measurement results due to differences in how the measurement site is placed on the device, and can perform highly accurate measurements stably.

[0041] In another aspect, in any of the above aspects, the height of the base in a direction perpendicular to the main surface may be varied prior to the measurement to adjust the position of the living body relative to the light irradiation unit.

[0042] In another aspect, in any of the above aspects, prior to the measurement, the position of the photodetector may be changed in a direction intersecting with the optical path of the signal light, and the position of the photodetector relative to the living body in that direction may be adjusted.

[0043] In another aspect, in any of the above aspects, prior to the target measurement, a reference measurement may be performed in which the angle of the principal surface is changed within a plane defined by the optical path of the laser light and the optical path from the subject part to the photodetector, and the concentration of the blood substance in the specific region is measured, thereby simultaneously adjusting the first angle and the second angle based on the concentration of the blood substance.

[0044] In another aspect, in any of the above aspects, prior to the target measurement, the position of the photodetector relative to the living body in that direction may be adjusted by performing a reference measurement in which the position of the photodetector is changed along the optical path of the signal light and the concentration of the blood substance is measured, and in this adjustment, the position of the photodetector may be adjusted based on the concentration of the blood substance so that the image of the signal light emitted from the vascular region Mp is transferred by the imaging lens and imaged on the light receiving surface of the photodetector.

[0045] In another aspect, in any of the above aspects, when the laser light is a first laser light, the blood substance is a first blood substance, and the concentration of the blood substance is the concentration of a first blood substance, in the reference measurement, the light irradiation unit irradiates the irradiation area with a second laser light for reference measurement that is absorbed by a second blood substance that is a reference substance, the imaging lens is used to form an image of signal light of the second laser light reflected from the specific area on the photodetector, the photodetector receives the signal light of the second laser light, and the concentration of the second blood substance based on the signal light is measured as the concentration of the second blood substance in the measurement target area, and the configuration may be such that the absorption rate of the second laser light by the second blood substance is greater than the absorption rate of the first laser light by the first blood substance in the target measurement.

[0046] A program according to an embodiment of the present disclosure is a program that causes a computer to perform a blood substance concentration measurement process for measuring the concentration of a blood substance contained in the blood of a subject part of a living organism, wherein the blood substance concentration measurement process includes: placing the living organism on a main surface of a base; and using a light irradiator from the main surface side of the base, concentrating and irradiating target measurement laser light that is absorbed by the blood substance, which is the measurement target substance, onto a specific region of the subject part that is on the skin surface facing the main surface of the living organism and in the skin located on the opposite side of the living organism; using an imaging lens located between the subject part and a photodetector on the main surface side of the base, forming an image of signal light, which is reflected light of the laser light and is emitted from a laser light concentration region in the subject part, with the intensity of light of some wavelengths of the laser light weakened, on a photodetector; receiving the signal light with the photodetector, and measuring the concentration of the blood substance in the specific region based on the intensity of the signal light; a first angle formed by a normal to the skin surface of the subject and the optical path of the laser light is different from a second angle formed by the normal and the optical path of the signal light from the specific region to the photodetector; the position of the living body relative to the light irradiation unit is defined so that a blood vessel region located inside the epidermis in the subject and the laser light focusing region overlap; and the position of the photodetector relative to the living body is defined so that an image of the signal light emitted from the blood vessel region overlapping with the laser light focusing region is transferred by the imaging lens and focused on the light receiving surface of the photodetector.

[0047] With this configuration, it is possible to provide a program that can suppress changes in measurement results due to differences in how the measurement site is placed on the device, and that can stably perform highly accurate measurements.

[0048] Embodiment 1 A blood substance concentration measuring device 1 according to this embodiment will be described with reference to the drawings. In this specification, the positive height direction may be referred to as the "up" direction, and the negative height direction may be referred to as the "down" direction. 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. The scales of the components in the drawings are not necessarily the same as those of the actual components. Furthermore, "perpendicular" and "parallel" may have an angle difference from 90° or 0°, respectively, as long as the functionality is not substantially impaired. Furthermore, in this specification, the symbol "to" used to indicate a numerical range includes both the values ​​at both ends. Furthermore, the materials, values, etc. described in this embodiment are merely preferred examples and are not limited thereto.

[0049] <Overall Configuration> 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 organism in a vascular region by irradiating a vascular region of the living organism with laser light of a specific wavelength from a light source and detecting the intensity of signal light emitted from the vascular region. The laser light used is light of a specific wavelength that can be absorbed by the substance to be measured. When the blood substance concentration is high, absorption by the substance causes the vascular region to emit signal light in which the intensity of light of some wavelengths is weakened compared to the irradiated laser light, and therefore device 1 measures the blood substance concentration by measuring the intensity of the signal light with a photodetector.

[0050] 1 is a schematic diagram showing the state of measurement by the device 1. The device 1 is a blood substance concentration measurement device configured such that, when a subject inserts a living subject Ob (e.g., a finger) into an opening 1a provided on the front surface of the device 1 and places the living subject Ob on a main surface 10a of a base 10 inside the device 1, laser light L1 is irradiated from a light irradiating unit 20 arranged on the main surface 10a side of the base 10 to a skin surface of the living subject Ob facing the main surface 10a and a living subject Mp0 located in the skin on the opposite side of the living subject Ob, and signal light L2 reflected from the living subject Mp0 is received by a photodetector 30 arranged on the main surface 10a side of the base 10 to perform measurement.

[0051] Fig. 2 is a schematic diagram showing the configuration of the apparatus 1. As shown in Fig. 2, the apparatus 1 includes a base 10, a light irradiation unit 20, a photodetector 30, a condenser lens 50, an imaging lens 40, a measurement control unit 60, a light detection unit 70, and an aperture 80.

[0052] The configuration of each part of the device 1 will be described below.

[0053] <Configuration of Each Part> (Base 10) The base 10 is a plate-like member on whose principal surface 10a, which is the surface facing upward, the living body Ob is placed during measurement. The base 10 is a guide member that stabilizes the position of the subject part Mp0 of the living body Ob during measurement and regulates the vascular region Mp included in the subject part Mp0 of the living body Ob to a predetermined position and angle suitable for irradiation with the laser light L1.

[0054] FIG. 3 is an enlarged view showing a portion of the living body placed on the base in FIG.

[0055] In this embodiment, the fingers of the living body Ob are placed with the palm surface of the fingers in contact with the main surface 10a, and measurement is performed on the back side of the fingers as the subject part Mp0. That is, when viewed from the skin surface of the living body Ob facing the main surface 10a, the subject part Mp0 is present in the skin located on the opposite side of the living body Ob from the skin surface (A1 in FIGS. 2 and 3 ).

[0056] Measurement positions are marked on the main surface 10a of the base 10, and by aligning the living body Ob with the markings and bringing the palmar surfaces of the fingers of the living body Ob into contact with the main surface 10a, it is possible to hold the test subject Mp0 in the skin on the back of the fingers of the living body Ob at a predetermined distance from the main surface 10a of the base 10. Furthermore, the position of the markings on the main surface 10a is specified so that the test subject Mp0 of the living body Ob aligned with the markings will be at a predetermined position with respect to the light irradiation unit 20 and the photodetector 30 when the angle of the main surface 10a is restricted to a predetermined angle.

[0057] The base 10 is also arranged so that the laser light L1 emitted from the light irradiator 20 enters from the main surface 10a side. The angle of the main surface 10a relative to the light irradiator 20 is regulated so that the incident angle A of the laser light L1 on the subject part Mp0 of the living body Ob is a predetermined angle θA.

[0058] Here, the incident angle A refers to the angle θA of the optical path Op1 of the laser light L1 from the light irradiation unit 20 to the area of ​​the subject part Mp0 where the laser light L1 is focused (hereinafter, sometimes referred to as the "laser light focusing area FA"), based on the normal to the skin surface of the living body Ob placed on the main surface 10a of the base 10.

[0059] At the same time, the base 10 regulates the angle of the main surface 10a relative to the photodetector 30 so that the installation angle B of the photodetector 30 relative to the object part Mp0 of the living body Ob is a predetermined angle θB.

[0060] Here, the installation angle B refers to the angle of the optical path Op2 of the signal light L2 from the laser light focusing area FA in the subject part Mp0 to the photodetector 30, with respect to the normal to the skin surface of the living body Ob placed on the main surface 10a of the base 10. In this case, the angle θA is different from the installation angle B.

[0061] That is, in the device 1, the position of the light irradiator 20 is restricted relative to the main surface 10a of the base 10, and at the same time, the position of the photodetector 30 is restricted via a movable mechanism 71 (described later) relative to the main surface 10a of the base 10 and the light irradiator 20. Therefore, the device 1 can be configured so that the installation angle B becomes a predetermined angle θB when the incident angle A becomes a predetermined angle θA.

[0062] By using a base 10 having such a configuration, simply by contacting the palm surface of the fingers of the living body Ob with the main surface 10a, the incident angle A of the laser light L1 relative to the subject part Mp0, the installation angle B of the photodetector 30 relative to the subject part Mp0, and the position at which the laser light L1 is irradiated onto the subject part Mp0 can be roughly regulated to near the appropriate values ​​required for measurement.

[0063] Furthermore, the base 10 is configured with a rotation stage mechanism 11 that changes the angle θC of the main surface 10a with respect to the optical paths of the laser light L1 and the signal light L2 within a plane (hereinafter sometimes referred to as the "laser light incident plane") defined by the optical path of the laser light L1 irradiated from the light irradiation unit 20 and the optical path of the signal light L2 from the subject area to the photodetector 30.

[0064] The rotating stage mechanism 11 is equipped with an angle change mechanism incorporating a motor, and the motor is driven by a control signal issued from the measurement control unit 60, which operates the angle change mechanism to change the angle θC of the main surface 10a and outputs information about the angle θC to the measurement control unit 60.

[0065] This rotating stage mechanism 11 allows the incident angle A and the installation angle B with respect to the subject part Mp0 to be simultaneously adjusted to match the shape or size of the individual living body Ob, even if the shape of the skin surface of the living body Ob differs depending on the subject.

[0066] In this case, when the living body Ob is aligned with the marking on the main surface 10a, the positional relationship between the main surface 10a, the center of rotation of the rotating stage mechanism 11, and the optical path of the laser light L1 may be specified so that, as the angle θC changes due to rotation, the direction in which the subject part Mp0 located in the skin on the back of the finger moves becomes approximately parallel to the normal direction to the skin surface on the back of the finger.

[0067] This makes it possible to prevent the position at which the laser light L1 is irradiated on the living body Ob from changing when the angle θC is changed to adjust the incident angle A and the installation angle B with respect to the object Mp0.

[0068] The base 10 is also configured with a height adjustment mechanism 12 so that the height ht in a direction perpendicular to the main surface 10a can be varied. The height adjustment mechanism 12 can be, for example, a lead screw or a well-known linear motion mechanism such as a linear motor. The height adjustment mechanism 12 is driven by a control signal issued from the measurement control unit 60, and operates the linear motion mechanism to change the height ht of the base 10, while outputting information about the height ht to the measurement control unit 60.

[0069] The height adjustment mechanism 12 can adjust the positional relationship of the subject part Mp0 in the living body Ob with respect to the light irradiation unit 20 in accordance with the shape or size of the individual living body Ob so that the laser light is focused and irradiated onto the blood vessel region Mp located inward from the epidermis of the subject part Mp0. This restricts the position of the living body Ob with respect to the light irradiation unit 20 so that the blood vessel region Mp located inward from the epidermis of the subject part Mp0 and the laser light focusing region FA overlap in the XZ plane.

[0070] Furthermore, by adjusting the height ht using the height adjustment mechanism 12, it is possible to absorb fluctuations in the distance from the main surface 10a to the subject part Mp0 (located in the skin on the back of the finger of the living body Ob) caused by the thickness of the finger of the living body Ob, thereby absorbing variations in the thickness of the finger of the living body Ob that differ from subject to subject.

[0071] As a result, even if the fingers of the subject's living body Ob are thick (or thin), by adjusting the height ht using the height adjustment mechanism 12 in a direction that compensates for the excess or deficiency in the thickness of the fingers, the position at which the laser light L1 is irradiated onto the subject part Mp0 of the living body Ob, the incident angle A of the laser light L1 relative to the subject part Mp0, and the installation angle B of the photodetector 30 relative to the subject part Mp0 can be restricted to near the appropriate values ​​required for measurement.

[0072] (Light Irradiation Unit 20) The light irradiation unit 20 is a light source that irradiates a laser light L1 of a specific wavelength toward the subject portion Mp0 of the living body Ob. The light irradiation unit 20 is configured to be able to irradiate a laser light for measurement (hereinafter, sometimes referred to as "first laser light") that oscillates at a wavelength that is absorbed by a first blood substance (hereinafter, sometimes referred to as "first blood substance") that is a measurement target substance.

[0073] Furthermore, in the device 1, the light irradiating unit 20 is configured to selectively irradiate the laser light for reference measurement (hereinafter sometimes referred to as "second laser light"), which oscillates at a wavelength that is absorbed by a second blood substance (hereinafter sometimes referred to as "second blood substance") that is the reference substance, with the laser light for target measurement. This allows for different types of detectable blood substances.

[0074] 4 is a schematic diagram showing the configuration of the light irradiation unit 20 in the blood substance concentration measurement device 1. As shown in FIG. 4, the light irradiation unit 20 includes a light source 21 that oscillates pump light L0 having a wavelength shorter than pulsed mid-infrared light, and an optical parametric oscillator (OPO) 22 that converts the pump light L0 to a longer wavelength, amplifies it, and emits it as laser light L1. In the OPO 22, the pump light L0 is incident on an internal nonlinear optical crystal, which oscillates light of two different wavelengths to generate signal light of a short wavelength and idler light of a long wavelength.

[0075] The light irradiating unit 20 outputs the idler light as laser light L1 to a subsequent stage and uses it to measure blood glucose levels. The optical parametric oscillator 22 may have a configuration described in a known document, for example, Japanese Patent Application Laid-Open No. 2010-281891.

[0076] In this embodiment, for example, glucose can be used as the first blood substance to be measured. In this case, the irradiated laser light is light of a wavelength selected from mid-infrared light, and mid-infrared light is used as the wavelength oscillated by optical parametric oscillation, as it is a wavelength that is more highly absorbed by glucose than the conventionally used near-infrared light. The predetermined wavelength may be selected from the range of 2.5 μm to 12 μm. More preferably, the predetermined wavelength is selected from the range of 6.0 μm to 12 μm.

[0077] Specifically, in this embodiment, the selected wavelength is 9.26 μm. For example, it may be 9.26±0.05 μm (9.21 μm or more and 9.31 μm or less). Alternatively, the wavelength may be selected in the range of −0.05 μm or more and +0.05 μm or less, based on 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.

[0078] This allows the glucose concentration in the subject's blood to be measured as a blood glucose level. In this case, it is necessary to measure the glucose concentration in the blood vessels inside the skin, and mid-infrared light, which does not easily penetrate deep into the body, is irradiated directly onto the blood vessels (capillaries) inside the skin.

[0079] Since mid-infrared light has a lower transmittance into the body than near-infrared light, which has traditionally been used to measure blood glucose levels, it is possible to identify the location of blood vessels inside the skin and irradiate them with mid-infrared light, thereby enabling observation of only the blood vessels, with the advantage of being less affected by other biological components present deep inside.Furthermore, the use of mid-infrared light reduces the adverse effects on measurement caused by overlapping harmonics and combination tones of the normal vibration, resulting in more accurate glucose measurement than near-infrared light.

[0080] On the other hand, the reference substance (second blood substance) to be subjected to the reference measurement is selected to have a higher absorption rate of laser light than the substance to be measured, and therefore a blood substance with high measurement sensitivity, high stability of blood concentration, and small variability in measurement results.

[0081] That is, it is preferable that the absorption rate of the laser light in the reference measurement by the reference substance (second blood substance) is greater than the absorption rate of the laser light for the object measurement by the measurement target substance (first blood substance) in the object measurement, and / or that the reference substance (second blood substance) has a more stable concentration in blood than the measurement target substance (first blood substance).

[0082] By performing a reference measurement on the reference substance having such a configuration and then performing an object measurement, the measurement accuracy of the measurement object can be improved.

[0083] In this embodiment, hemoglobin can be selected as an example of the reference substance (second blood substance). By detecting hemoglobin in blood vessels, the position of capillaries in the living body can be detected, and the optimal position of the measurement target portion Mp in the test portion Mp0 in the living body Ob can be identified when measuring the measurement target substance (first blood substance).

[0084] When the first blood substance or the second blood substance is hemoglobin, the laser light to be irradiated for measurement is light of a wavelength selected from mid-infrared light, and has a predetermined wavelength selected from the range of 5.0 μm or more and 12 μm or less.

[0085] Specifically, for example, the wavelength may be 8.00±0.1 μm (7.9 μm or more and 8.1 μm or less). Alternatively, the wavelength may be selected from the range of 5.26 μm or more and 6.76 μm or less, the range of −0.1 μm or more and +0.1 μm or less with 7.17 μm as the reference, the range of −0.1 μm or more and +0.1 μm or less with 7.58 μm as the reference, the range of 7.58 μm or more and 8.33 μm or less, or the range of −0.1 μm or more and +0.1 μm or less with 8.55 μm as the reference.

[0086] The light source 21 may be equipped with a Q-switched Nd:YAG laser (oscillation wavelength: 1.064 μm) or a Q-switched Yb:YAG laser (oscillation wavelength: 1.030 μm). This allows for pulsed oscillation of pump light L0, which has a wavelength shorter than mid-infrared light. The pump light L0 may have a pulse width of approximately 8 ns and a frequency of 10 Hz or higher, for example.

[0087] Furthermore, with a Q-switched Nd:YAG laser or Yb:YAG laser, the light source 21 can be simplified and made smaller because it operates as a passive Q-switch that performs a passive switching operation using a saturable absorber.

[0088] 4, the optical parametric oscillator 22 includes an incident-side semi-mirror 221, an exit-side semi-mirror 222, and a nonlinear optical crystal 223. The nonlinear optical crystal 223 is disposed in an optical resonator in which the incident-side semi-mirror 221 and the exit-side semi-mirror 222 face each other. Light L01 transmitted through the incident-side semi-mirror 221 enters the nonlinear optical crystal 223 and is converted into light with 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.

[0089] For the nonlinear optical crystal 223, AgGaS, which is 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 of nonlinear optical crystal 223 and the matching conditions. GaSe, ZnGeP2, CdSiP2, LiInS2, LiGaSe2, LiInSe2, LiGaTe2, etc. may also be used as the nonlinear optical crystal. The laser light L1 emitted from the optical parametric oscillator 22 has a repetition frequency corresponding to the pump light L0, for example, a pulse width of approximately 8 ns, and the short pulse width allows for high intensity peak output of 10 W to 1 kW.

[0090] In this way, the light irradiation unit 20 uses the light source 21 and the optical parametric oscillator 22, and thus, the light irradiation unit 20 can achieve 10 times the light intensity compared to a conventional light source such as a quantum cascade laser. 3 ~10 5 It is possible to obtain a laser beam L1 having an intensity about twice as high as that of the conventional laser beam L1.

[0091] In order to change the wavelength of the light emitted by the light irradiation unit 20, the oscillation wavelength of the optical parametric oscillator 22 of the light irradiation unit 20 can be changed to a different mode, thereby changing the phase matching condition of the nonlinear crystal 223 in the optical parametric oscillator 22, or the device can be realized by changing the optical parametric oscillator 22 that has a different phase matching condition of the nonlinear crystal 223.

[0092] This configuration enables blood glucose measurement using mid-infrared light, which has low transmittance into the body.

[0093] The light irradiating unit 20 is electrically connected to a measurement control unit 60 (described later), and outputs laser light L1 based on a control signal from the measurement control unit 60 .

[0094] 2, a condenser lens 50 (sometimes referred to as a "second lens" in this specification) for condensing the irradiated light onto a specific region in the subject part Mp0 is arranged on the optical path Op1 of the laser light L1 from the light irradiator 20 to the subject part Mp0 of the living body Ob. In the section on the optical path Op1 from the light irradiator 20 to the surface of the living body Ob, the laser light L1 is configured to propagate through space, such as gas, except for the section passing through the condenser lens 50.

[0095] In the device 1, when the palm surface of the fingers of the living body Ob is placed in a predetermined position on the main surface 10a, the condenser lens 50 is optically designed so that the laser light L1 emitted from the light irradiation unit 20 located on the main surface 10a side of the base 10 is condensed and irradiated onto a specific area in the subject part Mp0 located on the opposite side of the skin surface facing the main surface 10a of the living body.

[0096] Furthermore, the optical design is such that the region where the laser light L1 is focused is set at a depth corresponding to a blood vessel region Mp located inward from the epidermis in the subject portion Mp0, for example, a biological portion located inward from the epidermis, such as the dermis. In this specification, as described above, the region in the subject portion Mp0 where the laser light L1 is focused is referred to as a laser light focusing region FA.

[0097] The incident angle A of the laser light L1 onto the subject part Mp0 is determined by the angle of the optical path Op1 of the laser light L1 from the light irradiation part 20 to the laser light concentration area FA, based on the normal to the part where the laser light L1 is incident on the skin surface of the living body Ob placed on the main surface 10a of the base 10.

[0098] In this embodiment, the incident angle θA may be, for example, 45 degrees or more, or may be 60 degrees or more and 70 degrees or less.

[0099] 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, which may then be used for normalizing the detection signal in the photodetector 30. The output of the photodetector 30 can be compensated based on the fluctuations in the intensity of the laser light L1.

[0100] The laser light L1 that passes through the focusing lens 50 is incident on the living body Ob on the main surface 10a of the base 10, passes through the epithelial interstitial tissue of the living body, is scattered or diffusely reflected, and passes through the base 10 again as signal light L2, which is emitted toward the photodetector 30.

[0101] (Aperture 80) The aperture 80 is disposed in the optical path Op1 of the laser light L1 from the light irradiation unit 20 to the subject part Mp0 of the living body Ob, in the section between the light irradiation unit 20 and the condenser lens 50. The aperture 80 is made of a plate-like member having light-blocking properties, and has an opening 80a (aperture) in the center.

[0102] The center of the opening 80a coincides with the optical axis of the laser light L1. The opening 80a may be configured to narrow the beam diameter of the laser light L1 to, for example, about 1 / 3.

[0103] The focusing lens 50 defines a distance between the light irradiation unit 20 and the aperture 80 as f ＩＮ , 1 / f ＩＮ = 1 / a ＩＮ +1 / b ＩＮ When this is the case, a ＩＮ :b ＩＮ Alternatively, the two electrodes may be arranged at a position that divides the two electrodes into two.

[0104] In this way, by providing the diaphragm 80 between the light irradiating unit 20 and the condenser lens 50 in the optical path Op1, it is possible to reduce variations in the irradiation position of the laser light L1 irradiated onto the living body Ob.

[0105] 5 is a diagram for explaining an overview of the light-receiving side optical path in the device 1, and is a schematic diagram depicting a cross-sectional view of the subject portion Mp0 of the living body Ob and the screen 30a of the photodetector 30. As shown in FIGS. 2 and 5 , an imaging lens 40 (sometimes referred to as a “first lens” in this specification) is arranged in the optical path Op2 of the signal light L2 from the laser beam focusing area FA in the subject portion Mp0 of the living body Ob to the photodetector 30. The imaging lens 40 is diffusely reflected at the laser beam focusing area FA in the subject portion Mp0, and focuses the signal light L2 emitted from the laser beam focusing area FA on the photodetector 30.

[0106] In the optical path Op2, the signal light L2 is configured to propagate through space in the section from the surface of the living body Ob including the object part Mp0 to the photodetector 30, except for the section passing through the condenser lens 50.

[0107] The imaging lens 40 is optically designed so that an image Im1 of the signal light L2 emitted by diffuse reflection from the area where the vascular area Mp in the subject area Mp0 overlaps with the laser light focusing area FA is transferred by the imaging lens 40 and imaged as an image Im2 on the screen 30a of the photodetector 30.

[0108] In this embodiment, the distance Op21 between the center of the imaging lens 40 and the laser light focusing area FA 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.

[0109] This creates a positional relationship in which an image Im1 at a depth corresponding to the vascular region Mp in the subject part Mp0 irradiated with mid-infrared light is transferred as an image Im2 of equivalent size onto the screen 30a of the photodetector 30.

[0110] Here, the blood vessel region Mp is located in a portion of the living body that is located inward from the epidermis, such as the dermis (hereinafter sometimes referred to as an "inner portion of the living body"). In this embodiment, the depth corresponding to the blood vessel region Mp may be, for example, 0.5 mm or more and 3.5 mm or less, or may be, for example, 1.5 mm. In this case, when the focal length of the focal point Fp of the imaging lens 40 is f, the distances Op21 and Op22 may both be 2f.

[0111] However, the lengths of distances Op21 and Op22 are not limited to those described above, and the magnifications of distances Op21 and Op22 can be set so that the image Im1 of the base 10 irradiated with mid-infrared light fits just enough within the screen 30a of the photodetector 30, and the imaging lens 40 can be set to achieve that magnification.

[0112] The angle of incidence of the signal light L2 on the imaging lens 40 is determined by the angle of the optical axis of the signal light L2, which passes through the center of the imaging lens 40, relative to a normal to the portion of the skin surface of the subject Mp0 from which the signal light L2 is emitted. The angle of the optical axis passing through the center of the imaging lens 40 is equal to the installation angle B of the photodetector 30 with respect to the skin surface of the living body Ob described above, and in this embodiment may be, for example, between 0 degrees and 40 degrees, and more preferably between 20 degrees and 30 degrees.

[0113] (Optical detection unit 70) The blood substance concentration measuring device 1 is configured so that, while the light irradiating unit 20 is irradiating the second laser light for reference measurement, the photodetector 30 is moved along the optical path Op2 of the signal light L2 from the subject portion Mp0 to the photodetector 30 to vary the distance of the photodetector 30 from the imaging lens 40. The photodetector 30 is also configured to be able to adjust the positional relationship between the laser light condensing area FA and the photodetector 30 in the direction perpendicular to the optical path Op2 by moving the photodetector 30 in a direction intersecting the optical path Op2 of the signal light L2 from the laser light condensing area FA in the subject portion Mp0 to the photodetector 30 at a predetermined angle, for example, in a substantially perpendicular direction. In this case, the photodetector 30 may be configured to be moved in a direction along the optical path Op1 of the laser light L1.

[0114] [Photodetector 30] The photodetector 30 is a near-infrared and mid-infrared sensor that receives the signal light L2 emitted from the laser light focusing area FA based on the irradiated laser light L1 and detects the intensity of the signal light L2. The photodetector 30 outputs an electrical signal corresponding to the intensity of the received signal light L2. The photodetector 30 may be, for example, an infrared sensor consisting of a single element that outputs the intensity of the signal light L2 as a one-dimensional voltage value.

[0115] In the device 1, the light irradiation unit 20 increases the intensity of the irradiated laser light L1, and the imaging lens 40 forms an image of the signal light L2 emitted from the laser light focusing area FA on the screen 30a of the photodetector 30, so that the photodetector 30 can receive signal light of a sufficiently high intensity compared to the background light, achieving a high S / N ratio and enabling high-precision measurements.

[0116] In this way, since the laser light L1 and the signal light L2 are monochromatic and have high intensity, the only processing required for the photodetector 30 is to detect 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.

[0117] It should be noted that a liquid nitrogen-cooled HgCdTe infrared photodetector may be used as the photodetector 30. In this case, by cooling the detector to approximately 77 K with liquid nitrogen, the intensity of the signal light L2 can be detected with a higher S / N ratio.

[0118] The photodetector 30 is electrically connected to the measurement control unit 60 described later, and outputs the intensity of the received signal light to the measurement control unit 60 as a one-dimensional voltage value based on a control signal from the measurement control unit 60.

[0119] [Movable mechanism 71] The movable mechanism 71 is composed of a first linear transport mechanism 711 that can reversibly move the photodetector 30 along the optical path Op2 of the signal light L2 from the subject portion Mp0 to the photodetector 30, and a second linear transport mechanism 712 that can reversibly move the photodetector 30 in a direction perpendicular to the optical path Op2.

[0120] The first linear transport mechanism 711 can adjust the position of the signal light L2 parallel to the optical path Op2 leading to the photodetector 30 so that an image Im1 at a depth corresponding to the blood vessel region Mp in the subject part Mp0 is transferred as an image Im2 of equivalent size to the screen 30a of the photodetector 30. The first linear transport mechanism 711 may also be configured to reversibly move the imaging lens 40 along the optical path Op2 together with the photodetector 30.

[0121] Furthermore, by the function of the second linear conveying mechanism 712, the position of the photodetector 30 can be adjusted so that the center of the screen 30a of the photodetector 30 and the position where the laser light L1 is focused and irradiated onto the subject part Mp0 (laser light focusing area FA) roughly coincide or overlap in a direction perpendicular to the optical path Op2 of the signal light L2 reaching the photodetector 30.

[0122] The first linear conveying mechanism 711 and the second linear conveying mechanism 712 can be general-purpose linear conveying mechanisms such as linear motors, lead screws, ball screws, rack and pinions, etc. Alternatively, instead of using the linear conveying mechanisms 711 and 712, a reflecting mechanism (mirror) equipped with a MEMS (Micro Electro Mechanical Systems) actuator using a piezoelectric element may be inserted into the laser optical path to change the laser optical path and switch to the correct detector position. The movable mechanism 71 is electrically connected to the measurement control unit 60 (described later) and conveys the photodetector 30 to a predetermined position based on a control signal supplied from the measurement control unit 60.

[0123] For example, the first linear transport mechanism 711 is driven by a control signal issued from the measurement control unit 60, operates the linear motion mechanism to change its position in a direction parallel to the optical path Op2 to the photodetector 30, and outputs position information in that direction to the measurement control unit 60. Similarly, the second linear transport mechanism 712 is driven by a control signal issued from the measurement control unit 60, operates the linear motion mechanism to change its position in a direction perpendicular to the optical path Op2 to the photodetector 30, and outputs position information in that direction to the measurement control unit 60.

[0124] Furthermore, the device 1 may be configured such that, in conjunction with the operation of varying the height ht in the direction perpendicular to the main surface 10a by the height adjustment mechanism 12, the second linear transport mechanism 712 changes the position in the direction perpendicular to the optical path Op2 to the photodetector 30. This makes it possible to vary and adjust the irradiation position of the laser light L1 on the skin surface of the dorsal surface of the finger in the direction parallel to the center line of the finger. Details will be described later.

[0125] (Measurement control unit 60) The measurement control unit 60 is a circuit that is electrically connected to the light irradiation unit 20, the photodetector 30, and the movable mechanism 71, 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 signal light L2 based on the output signal from the photodetector 30, to calculate the blood substance concentration in the vascular region Mp in the subject part Mp0.

[0126] Alternatively, at this time, the measurement 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 output of the monitor photodetector may be used to normalize the output of the photodetector 30, thereby compensating for the effect of fluctuations in the intensity of the laser light L1 and calculating the concentration of a substance in the blood.

[0127] The measurement control unit 60 is also electrically connected to the rotation stage mechanism 11 and height adjustment mechanism 12 of the base 10, and functions as a control circuit that drives these. That is, the measurement control unit 60 outputs a control signal to the base 10 to drive the rotation stage mechanism 11 of the base 10 and adjust the angle of incidence A with respect to the test part Mp0, and also drives the height adjustment mechanism 12 of the base 10 to change the height ht in the direction perpendicular to the main surface 10a, thereby adjusting the position at which the laser light L1 is irradiated with respect to the test part Mp0.

[0128] Furthermore, the measurement control unit 60 is electrically connected to the movable mechanism 71 and functions as a control circuit that drives the first linear transport mechanism 711 and the second linear transport mechanism 712. That is, the measurement control unit 60 outputs a control signal to the movable mechanism 71 to drive the first linear transport mechanism 711 to transport the photodetector 30 to a predetermined position along the optical path Op2 of the signal light L2, and also drives the second linear transport mechanism 712 to transport the photodetector 30 to a predetermined position in a direction perpendicular to the optical path Op2 of the signal light L2. The first linear transport mechanism 711 may also be configured to reversibly move the imaging lens 40 along the optical path Op2 together with the photodetector 30.

[0129] The measurement control unit 60 may be configured to include, for example, a control unit (not shown) incorporating a CPU (Central Processing Unit) and a data storage unit (not shown).

[0130] The data storage unit includes a volatile memory such as a dynamic random access memory (DRAM) and a nonvolatile memory such as a hard disk. The output signal acquired by the photodetector 30 is transmitted to and stored in the data storage unit. Information on the angle θC output from the rotating stage mechanism 11, information on the height ht output from the height adjustment mechanism 12, position information of the photodetector 30 parallel to the optical path Op2 output from the first linear transport mechanism 711, and position information of the photodetector 30 perpendicular to the optical path Op2 output from the second linear transport mechanism 712 are also transmitted and stored. Blood substance concentrations calculated by the control unit may also be stored. The data storage unit stores programs and other information necessary for executing the functions of the device 1, and also functions as a temporary storage area for temporarily storing calculation results from the control unit.

[0131] The CPU realizes the functions of the device 1 by reading and executing a program from the data storage unit.

[0132] As a result, the measurement control unit 60 performs the operations described above, such as transporting the photodetector 30, irradiating the laser light L1 from the light irradiation unit 20, and calculating the blood substance concentration based on the signal from the photodetector 30, based on a predetermined program, in the blood substance concentration measurement process described below.

[0133] <Effects of the blood substance concentration measuring device 1> (Realization of a configuration that enables stable, highly accurate measurements by irradiating laser light from the main surface 10a side) With the above-described configuration, the device 1 can irradiate laser light L1 onto the subject part Mp0 of the living body Ob from the main surface 10a side of the base 10 on which the living body Ob is placed, and receive reflected light based on the laser light L1 on the main surface 10a side to measure the blood substance concentration, thereby enabling stable, highly accurate measurements.

[0134] Specifically, in the device 1, the position of the light irradiation unit 20 is restricted with respect to the main surface 10a of the base 10, and at the same time, the position of the photodetector 30 is restricted via the movable mechanism 71 with respect to the main surface 10a of the base 10 and the light irradiation unit 20. Therefore, the device 1 can be configured so that the installation angle B becomes a predetermined angle θB when the incident angle A becomes a predetermined angle θA.

[0135] Furthermore, by providing a rotating stage mechanism 11 that changes the angle θC of the main surface 10a of the base 10, even if the shape of the skin surface of the living body Ob differs depending on the subject, the incident angle A and the installation angle B with respect to the subject part Mp0 can be simultaneously adjusted to suit the shape or size of the individual living body Ob.

[0136] Furthermore, by providing a height adjustment mechanism 12 capable of adjusting the height ht of the main surface 10a of the base 10, it is possible to absorb fluctuations in the distance from the main surface 10a to the subject part Mp0 located in the skin on the back of the fingers of the living subject Ob due to the thickness of the fingers of the living subject Ob, thereby absorbing variations in the thickness of the fingers of the living subject Ob that differ from subject to subject.

[0137] As a result, when the height ht is adjusted to suit the subject, the position at which the laser light L1 is irradiated onto the subject part Mp0 of the living body Ob, the incident angle A of the laser light L1 relative to the subject part Mp0, and the installation angle B of the photodetector 30 relative to the subject part Mp0 can be regulated to near the appropriate values ​​required for measurement.

[0138] This prevents the measurement results from changing due to differences in how the measurement area is placed on the device, which occurs in configurations where measurements are performed by abutting the measurement area against the light irradiation window, and enables highly accurate measurements to be performed stably.

[0139] (Improvement of S / N ratio) Improvement of the S / N ratio during measurement by the optical system of the device 1 will be described.

[0140] FIG. 6 is a schematic diagram showing an outline of the optical path from the light irradiation unit 20 to the photodetector 30 in the device 1.

[0141] As shown in Figure 6, in the device 1, the laser light L1 condensed and irradiated from the light irradiating unit 20 enters the living body Ob at an incident angle A (angle θA) along an optical path Op1 toward a specific region (laser light condensing region FA) in the inner part of the living body in the subject part Mp0, and is absorbed by substances in the blood in the vascular region Mp located in the inner part of the living body, and in addition to an image (Im1) of signal light L2 emitted from the inner part of the living body below the skin surface (laser light condensing region FA) in which the intensity of light of some wavelengths from the laser light L1 has been weakened, surface reflection from the skin surface occurs.

[0142] Of these, the device 1 is configured such that an image (Im1) of the signal light L2 emitted mainly from the laser light focusing area FA in the interior portion of the living body is focused on the screen 30a of the photodetector 30 by the imaging lens 40. For example, when the focal length of the imaging lens 40 is f, the optical distance OP21 between the laser light focusing area FA (blood vessel area Mp) and the imaging lens 40 is a, and the optical distance OP22 between the screen 30a of the photodetector 30 and the imaging lens 40 is b, the positional relationship between the laser light focusing area FA, the imaging lens 40, and the photodetector 30 is set so as to satisfy the relationship 1 / f = 1 / a + 1 / b.

[0143] Therefore, by positioning the screen 30a of the photodetector 30 at a position where the optical distance OP22 is b, the image (Im1) of the signal light L2 emitted from the laser light focusing area FA is clearly formed on the screen 30a, and the signal intensity detected by the photodetector 30 becomes a relatively high value.

[0144] In contrast, the light reflected from the skin surface enters the imaging lens 40, but because the angle of incidence on the imaging lens 40 is different from that of the signal light L2 from the laser light focusing area FA, the light is guided outside the range of the screen 30a of the photodetector 30, or even if the light is guided within the range of the screen 30a of the photodetector 30, it does not form an image (becomes blurred), reducing the amount of light and the signal strength detected by the photodetector 30.

[0145] That is, since the epidermis is slightly closer to the imaging lens 40 than the blood vessel region Mp, if the optical distance OP21 between the epidermis and the imaging lens 40 is a', then the image transfer position is position b', which satisfies 1 / f = 1 / a' + 1 / b'. Therefore, on the screen 30a placed at position b, the image from the epidermis is blurred and not clear, and as a result, the signal intensity detected by the photodetector 30 is relatively reduced.

[0146] As a result, the influence of surface reflection from the skin surface, which is detected as noise, on the optical measurement is small.

[0147] Therefore, in the device 1, an image (Im1) of the signal light L2 emitted from the laser light focusing area FA in the blood vessel area Mp (inner part of the living body) below the surface of the skin, which is the main measurement target, is transferred by the imaging lens 40 and focused on the screen 30a of the photodetector 30, and is reflected in the optical measurement by the photodetector 30, so that measurement results that are highly correlated with the blood glucose measurement results by SMBG (Self Monitoring of Blood Glucose) and have high reproducibility can be obtained.

[0148] If a lens were installed simply to collect diffused light (scattered light) and the photodetector 30 were located near its focal point, the signal light from the blood vessel region Mp (intravital portion) would be essentially the same as scattered light, making it difficult to distinguish it from scattered light from the skin surface. In contrast, by installing components such as the imaging lens 40 and photodetector 30 at a position where image transfer is possible and transferring the signal light L2 from the blood vessel region Mp (intravital portion), the amount of scattered light from the epidermis can be relatively reduced, and the S / N ratio of the signal light L2 can be improved.

[0149] In this way, the device 1 can reduce false signal (noise) components due to signal light scattered on the skin surface, and improve the S / N ratio in optical measurement.

[0150] (Regarding Detection of Blood Vessel Region in Subject Part Mp0) Improvement of measurement accuracy based on detection of blood vessel region Mp in subject part Mp0 by the optical system of device 1 will be described.

[0151] FIG. 7 is a schematic diagram for explaining the operation of adjusting the optical path length from the laser beam focusing area FA to the photodetector 30 by the device 1. As shown in FIG.

[0152] As shown in Figure 7, the device 1 is configured such that, while irradiating laser light (second laser light) L1 for reference measurement from the light irradiation unit 20, the first linear conveying mechanism 711 of the movable mechanism 71 moves the photodetector 30 along the optical path Op2 of the signal light L2 from the subject portion Mp0 to the photodetector 30, thereby adjusting the distance of the photodetector 30 from the imaging lens 40.

[0153] This configuration realizes the function of causing the images (Im11, Im12, Im13) of the signal light L2 formed on the screen 30a of the photodetector 30 to differ in the image source areas (IA1, IA2, IA3) extracted from the subject part Mp0.

[0154] Here, the image source regions (IA1, IA2, IA3) are focus regions in the object part Mp0 where the focal point Fp of the imaging lens 40 is aligned.

[0155] For example, by disposing the photodetector 30 at the position shown in Fig. 7, an image Im11 of the signal light L2 emitted from an image source area IA1 located in the blood vessel area Mp in the subject area Mp0 can be formed on the screen 30a. Since the image source area IA1 is located in the area where the laser light collection area FA and the blood vessel area Mp overlap, by disposing the photodetector 30 at the position shown in Fig. 7, an image Im11 of the signal light L2 emitted from the blood vessel area Mp in the subject area Mp0 can be formed on the screen 30a.

[0156] At this time, the image Im12 of the signal light L2 emitted from the image source area IA2 located in the dermis portion of the subject part Mp0 is originally formed in front of the screen 30a (Im22), so the image (Im22) on the screen 30a is blurred and unclear, and the detected signal intensity is relatively reduced.

[0157] Similarly, the image Im13 of the signal light L2 emitted from the image source area IA3 located in the epidermis portion of the subject part Mp0 is originally formed (Im23) deeper than the screen 30a, so the image (Im23) is not clear on the screen 30a and the detected signal intensity is relatively reduced.

[0158] With this function, while gradually moving the photodetector 30 along the optical path Op2 of the signal light L2, the signal light from the blood vessels is detected based on the signal light of the laser light (first laser light) for measuring the target, and the position of the photodetector 30 where the intensity of the signal light increases can be detected, thereby detecting the state in which the image source region, which should be the measurement target region for the concentration of blood substances, is located in the region in the living body where the blood vessel region Mp and the laser light focusing region FA overlap, i.e., the state in which the imaging lens 40 is focused on that region.

[0159] That is, the device 1 receives signal light L2 emitted from the laser light focusing area FA while irradiating laser light (second laser light) L1 for reference measurement, and measures the concentration of a reference substance (second blood substance) that has a higher laser light absorption rate and / or a more stable blood concentration than the substance to be measured (first blood substance), thereby detecting the state in which an image Im11 based on the signal light L2 emitted from the area where the laser light focusing area FA and the vascular area Mp overlap is formed on the photodetector 30.

[0160] As described above, while gradually moving the photodetector 30, signal light from the blood vessels can be detected based on the signal light of the laser light for measuring the object (first laser light).

[0161] (Regarding Appropriate Measurement Positions on the Skin Surface of a Living Body Ob) Reduction of measurement variability due to measurement positions on the skin surface of a living body Ob using the optical system of the device 1 will be described.

[0162] 8 is a diagram showing the laser light irradiation positions on the surface of a living body when measuring the concentration of a substance in blood using the device 1. Using the index finger as the living body Ob, measurement positions 1 are a center line toward the fingertip, a cutting line displaced by δ from the base of the nail toward the base of the finger, measurement positions 2 and 3 are offset by 3 mm above and below the center line on the paper, and measurement positions 4 and 5 are offset by 3 mm to the left and right on the cutting line on the paper, and at measurement positions 4 and 5, there is a large amount of laser light absorption by hemoglobin, and a vascular region Mp exhibiting a high hemoglobin concentration is present.

[0163] Furthermore, at planar measurement positions 4 and 5 where signal light indicating the vascular region Mp is detected, laser light for measuring the object (first laser light) is irradiated from the light irradiation unit 20, and the signal light at that measurement position is received by the photodetector 30, so that the concentration of the substance to be measured can be measured when the planar measurement position is included in the vascular region Mp in the subject part Mp0.

[0164] As a result, it is possible to consistently perform highly accurate measurements regardless of individual differences in the position of blood vessels in the planar direction between subjects and between measurements.

[0165] As described above, the device 1 is configured to define the laser light focusing area FA on the biological surface during measurement by setting the markings on the main surface 10a of the base 10 at predetermined positions in advance. Therefore, by varying the positions of the markings at the measurement positions on the main surface 10a in advance, the laser light focusing area FA on the biological surface during measurement can be adjusted. In the device 1, for example, the positions of the markings on the main surface 10a of the base 10 may be set in advance so that the laser light is irradiated onto measurement positions 4 and 5 during measurement. This makes it possible to consistently perform highly accurate measurements of the vascular region Mp as the measurement target.

[0166] Furthermore, the device 1 may be configured to vary the irradiation position of the laser light L1 in a direction parallel to the center line of the finger on the skin surface of the back of the finger (hereinafter, sometimes referred to as the "center line direction of the finger") by combining an operation of varying the height ht in a direction perpendicular to the main surface 10a using the height adjustment mechanism 12 and an operation of changing the position in a direction perpendicular to the optical path Op2 of the signal light L2 leading to the photodetector 30 using the second linear transport mechanism 712.

[0167] Specifically, for example, when the palm surface of a finger of the living body Ob is aligned with the marking on the main surface 10a, increasing the height ht of the main surface 10a moves the laser light concentration area FA toward the tip of the finger. Therefore, the second linear transport mechanism 712 moves the laser light concentration area FA in a direction perpendicular to the optical path Op2 to the photodetector 30 and closer to the light irradiation unit 20 so that the laser light concentration area FA and the center of the screen 30a of the photodetector 30 roughly coincide or overlap in a direction perpendicular to the optical path Op2 to the photodetector 30.

[0168] Conversely, for example, in the same state, when the height ht of the main surface 10a is reduced, the laser light concentration area FA moves toward the base of the fingers. Therefore, the second linear transport mechanism 712 moves the photodetector 30 in a direction perpendicular to the optical path Op2 and away from the light irradiation unit 20 so that the laser light concentration area FA and the center of the screen 30a of the photodetector 30 roughly coincide or overlap in a direction perpendicular to the optical path Op2 of the signal light L2.

[0169] Furthermore, in the measurement control unit 60, the height ht of the main surface 10a and the position in the direction perpendicular to the optical path Op2 may be stored in advance in a data storage unit or the like as a pair of combined information. Based on this information, the measurement control unit 60 may vary the laser light focusing area FA in the direction of the center line of the finger by concurrently performing an operation to vary the height ht using the height adjustment mechanism 12 and an operation to change the position of the photodetector 30 using the second linear transport mechanism 712.

[0170] <Operation of Blood Substance Concentration Measuring Device 1> Next, an outline of the operation of the device 1 will be described with reference to FIGS.

[0171] (Operation of Determining Whether or Not the Laser Light Convergence Area FA Belongs to the Blood Vessel Area Mp in the Subject Area Mp0) FIG. 9 is a flowchart showing one aspect of the operation of measuring substances in blood by the apparatus 1. In FIG.

[0172] In Figure 9, steps S11 to S12 are steps for performing a reference measurement in which the concentration of a reference substance (a second blood substance) in a specific area (laser light focusing area FA) irradiated with focused laser light L1 is measured, and whether or not the laser light focusing area FA is included in the vascular area Mp in the subject area Mp0 is determined.

[0173] Steps S21 and S22 are steps of subject measurement for measuring the concentration of a measurement target substance (first blood substance) in a state where the laser light focusing area FA is included in the blood vessel area Mp in the subject part Mp0.

[0174] 9, first, it is determined whether or not to perform a reference measurement (step S1). This determination may be made based on operational input from the operator or identification information such as the subject's ID. For example, when the same subject is repeatedly measured daily, the results of a reference measurement already obtained can be used, and the reference measurement can be omitted. If the determination in step S1 determines that a reference measurement will be performed (step S1: Yes), the process proceeds to step S11. If the determination in step S1 determines that a reference measurement will not be performed (step S1: No), the process proceeds to step S21.

[0175] Next, in steps S11 and S12, a reference measurement is performed. First, based on a control signal, the measurement control unit 60 causes the light irradiation unit 20 to irradiate a specific region in the subject Mp0 with focused laser light for reference measurement (second laser light) (step S11), measures the concentration of the reference substance (second blood substance) in the laser light focused region FA using the photodetector 30 (step S12), and determines whether the measured concentration of the reference substance is equal to or greater than a reference value (step S13).

[0176] In step S13, if the value is not equal to or greater than the reference value (step S13: No), the processing is terminated; if the value is equal to or greater than the reference value (step S13: Yes), it is determined that the laser light focusing area FA is included in the vascular area Mp in the subject part Mp0, and therefore the concentration of the substance to be measured (first blood substance) is measured in steps S21 to S22.

[0177] Specifically, the light irradiation unit 20 irradiates a specific area in the subject Mp0 with laser light for measuring the target (first laser light) (step S21), and the photodetector 30 measures the concentration of the substance to be measured (target measurement) in the laser light focusing area FA, outputs the measurement results (step S22), and ends the process.

[0178] (Operation of Adjusting the Position of the Photodetector Along the Optical Path) FIG. 10 is a flowchart showing another aspect of the operation of measuring a substance in blood by the blood substance concentration measuring device 1.

[0179] In Figure 10, steps S10 to S16 are steps in which the concentration of a reference substance (second blood substance) in a specific area irradiated with focused laser light L1 is measured as a reference measurement, and the position of the photodetector is adjusted along the optical path Op2 based on the concentration of the reference substance in the laser light focus area FA so that the laser light focus area FA is included in the vascular area Mp in the subject area Mp0.

[0180] Steps S21 and S22 are steps of measuring the concentration of a measurement target substance (first blood substance) when the laser light focusing area FA is included in the blood vessel area Mp in the subject part Mp0. The same steps as in Figure 9 are indicated by the same numbers as in Figure 9.

[0181] In FIG. 10 , if the determination in step S1 indicates that a reference measurement should be performed (step S1: Yes), the reference measurement is performed in steps S10 to S16. First, the measurement control unit 60 drives the first linear transport mechanism 711 of the movable mechanism 71 based on a control signal to move the photodetector 30 to the starting position (step S10). Then, the light irradiation unit 20 focuses and irradiates a specific region in the subject portion Mp0 with laser light for reference measurement (second laser light) (step S11). The photodetector 30 then measures the concentration of the reference substance (second blood substance) in the laser light focusing region FA (reference measurement, step S12). At this time, the measurement control unit 60 detects the light intensity of the signal light L2 based on the output signal from the photodetector 30, calculates and stores the concentration of the reference substance in the laser light focusing region FA. At the same time, the measurement control unit 60 stores the position information of the photodetector 30 in the direction of the optical path Op2 on the first linear transport mechanism 711.

[0182] Next, it is determined whether the photodetector 30 is at the end position (step S14), and if it is not at the end position (step S14: No), the position of the photodetector 30 is gradually moved (step S15) and the process returns to step S11, whereas if it is at the end position (step S14: Yes), the process proceeds to step S16, assuming that the measurement of the reference substance concentration in the laser beam focusing area FA has been completed for all the photodetectors 30. In this state, the measurement control unit 60 stores the position information of the photodetector 30 for all the positions of the photodetector 30 and the concentration of the reference substance in the laser beam focusing area FA.

[0183] In step S16, the measurement control unit 60 selects the optimal position where the highest concentration of the reference substance was obtained based on the concentration measurement results of the reference substance in the laser light collection area FA at all positions of the photodetector 30, and issues a control signal to the movable mechanism 71 to drive the first linear transport mechanism 711 to move the photodetector 30 to the optimal position. At the optimal position, it is estimated that the laser light collection area FA is included in the blood vessel region Mp in the subject portion Mp0. Note that even if the determination in step S1 indicates that reference measurement will not be performed (step S1: No), the photodetector 30 is moved to, for example, the predetermined optimal position in step S16.

[0184] Next, in steps S21 and S22, the concentration of the substance to be measured (first blood substance) is measured. Specifically, a laser beam for measuring the object (first laser beam) is focused and irradiated from the light irradiating unit 20 onto a specific region in the subject portion Mp0 (step S21), and the photodetector 30 measures the concentration of the measurement object in the laser beam focusing region FA, outputting the result (object measurement, step S22), and ending the process. (Operation of adjusting the irradiation position of the laser beam L1 in the planar direction) Figure 11 is a flowchart showing yet another aspect of the blood substance measurement operation by the blood substance concentration measuring device 1.

[0185] 11 , steps S10A to S16A are steps of measuring the concentration of a reference substance (second blood substance) in a specific region as a reference measurement by varying the planar position at which the laser light L1 is focused and irradiated in the subject region Mp0, and then adjusting the planar irradiation position based on the concentration of the reference substance at the different irradiation positions so that the irradiation position is included in the vascular region Mp in the planar direction in the subject region Mp0. In this example, a configuration will be described in which the planar position adjustment of the irradiation position of the laser light L1 is performed by varying the irradiation position of the laser light L1 in the direction of the center line of the finger.

[0186] Steps S21 and S22 are target measurement steps for measuring the concentration of a measurement target substance (first blood substance) in a state where the irradiation position is included in a vascular region Mp in the planar direction of the subject part Mp0.

[0187] The same processes as those in FIGS. 9 and 10 are indicated by the same numbers.

[0188] 11, if the determination in step S1 indicates that a reference measurement should be performed (step S1: Yes), the reference measurement is performed in steps S10A to S16A. First, the measurement control unit 60 moves the planar position of the laser light L1 (here, the position along the center line of the finger) to the starting position based on the control signal (step S10A). Then, the light irradiation unit 20 focuses and irradiates a specific region of the subject portion Mp0 with a laser light (second laser light) for reference measurement (step S11). The photodetector 30 then measures the concentration of the reference substance (second blood substance) in the laser light focusing region FA (step S12). Here, the device 1 varies the irradiation position of the laser light L1 along the center line of the finger by combining an operation of varying the height ht in the direction perpendicular to the main surface 10a using the height adjustment mechanism 12 and an operation of changing the position perpendicular to the optical path Op2 using the second linear transport mechanism 712.

[0189] First, the measurement control unit 60 detects the light intensity of the signal light L2 based on the output signal from the photodetector 30 at the start position, calculates and stores the concentration of the reference substance in the laser light focusing area FA, and simultaneously stores information on the height ht of the main surface 10a in the height adjustment mechanism 12 and the position information of the photodetector 30 in the direction perpendicular to the optical path Op2 in the second linear transport mechanism 712.

[0190] Next, it is determined whether the irradiation position is at the end point position (step S14). If it is not at the end point position (step S14: No), the irradiation position is changed (step S15A) and the process returns to step S11. If it is at the end point position (step S14: Yes), it is assumed that the measurement of the reference substance concentration in the laser beam focusing area FA at all irradiation positions has been completed and the process proceeds to step S16A. In this state, the measurement control unit 60 stores the position information of the photodetector 30 at all irradiation positions of the laser beam L1 in the center line direction of the finger, information on the height ht of the main surface 10a, and the concentration of the reference substance in the laser beam focusing area FA.

[0191] In step S16A, the measurement control unit 60 selects the optimal irradiation position at which the highest concentration of the reference substance (second) was obtained based on the blood concentration measurement results of the reference substance (second) in the laser light focusing area FA at all irradiation positions. The measurement control unit 60 then issues a control signal to drive the height adjustment mechanism 12 to change the height ht of the main surface 10a of the base 10 to a height corresponding to the optimal irradiation position, and issues a control signal to the movable mechanism 71 to drive the second linear transport mechanism 712 to move the photodetector 30 to a position corresponding to the optimal irradiation position, thereby changing the irradiation position of the laser light L1 to the optimal position. At the optimal position, the irradiation position is estimated to be included in the vascular region Mp in the planar direction of the subject Mp0. Note that even if the determination in step S1 determines that reference measurement will not be performed (step S1: No), the irradiation position of the laser light L1 is moved to, for example, the predetermined optimal position in step S16A.

[0192] Next, in steps S21 and S22, the concentration of the measurement target substance (first blood substance) is measured. Specifically, a laser beam for measuring the target (first laser beam) is focused and irradiated from the light irradiating unit 20 onto a specific region in the subject portion Mp0 (step S21), the photodetector 30 measures the concentration of the measurement target in the laser beam focusing region FA, and the result is output (target measurement, step S22), thereby ending the process.

[0193] <Summary> As explained above, the blood substance concentration measuring device 1 according to the first embodiment is a blood substance concentration measuring device 1 that measures the concentration of a blood substance contained in the blood of a subject portion Mp0 of a living organism Ob, and includes a base 10 on whose main surface 10a a living organism can be placed, a light irradiating unit 20 that condenses and irradiates laser light L1 from the main surface 10a side of the base 10 onto a specific region in the subject portion Mp0 that is located on the skin surface on the side facing the main surface 10a of the living organism and in the skin located on the opposite side of the living organism Ob, a photodetector 30 that receives, on the main surface 10a side of the base 10, signal light that is reflected light based on the laser light L1 and has light intensities of some wavelengths from the laser light L1 attenuated, and detects the intensity of that signal light, and a light irradiating unit 20 that is located between the subject portion Mp0 and the photodetector 30 and that forms an image of the signal light emitted from a laser light condensing region FA in the subject portion Mp0 on the photodetector 30. and a measurement control unit that measures the concentration of blood substances in the laser light focusing area FA based on the intensity of the signal light, wherein a first angle formed between a normal to the skin surface of the subject part Mp0 and an optical path Op1 of the laser light L1 is different from a second angle formed between the normal and an optical path Op2 from the laser light focusing area FA to the photodetector 30, the position of the subject part Mp0 in the living body Ob relative to the light irradiation unit 20 is defined so that a blood vessel area Mp located inside the epidermis in the subject part Mp0 overlaps with the laser light focusing area FA, and the position of the photodetector 30 relative to the subject part Mp0 in the living body Ob is defined so that an image of the signal light emitted from the blood vessel area Mp that overlaps with the laser light focusing area FA is transferred by the imaging lens 40 and focused on the light receiving surface of the photodetector.

[0194] Conventionally, blood substance concentration measuring devices have been configured to perform measurements by placing the area to be measured against a light irradiation window on the outer surface of the measuring device. Therefore, depending on how the area to be measured is placed on the light irradiation window, the pressure applied to the area to be measured and the measurement position can change, resulting in changes in the measurement results, making it difficult to obtain stable, sufficient measurement accuracy.

[0195] In contrast, with the above-described configuration of the device 1, laser light L1 is focused and irradiated from the main surface 10a of the base 10 onto a specific area in the subject part Mp0 located on the skin surface facing the main surface 10a of the living body and in the skin located on the opposite side of the living body Ob, and reflected light based on the laser light L1, i.e., signal light in which the intensity of light of some wavelengths from the laser light L1 is weakened, is received on the main surface 10a of the base 10 to measure the concentration of substances in the blood.This prevents the measurement results from changing depending on how the measured part is placed on the device, and enables stable, highly accurate measurements to be performed.

[0196] The base 10 may be configured so that the position of the living body Ob relative to the light irradiating unit 20 can be adjusted by varying the height of the main surface 10a in the direction perpendicular to the main surface 10a.

[0197] With this configuration, the positional relationship of the living body Ob with respect to the light irradiation unit 20 can be adjusted in accordance with the shape of the individual living body Ob so that the laser light is focused and irradiated onto the blood vessel region Mp located inward from the epidermis of the subject part Mp0. As a result, the position of the living body Ob with respect to the light irradiation unit 20 is regulated so that the blood vessel region Mp located inward from the epidermis of the subject part Mp0 and the laser light focusing region FA overlap in the XZ plane.

[0198] In addition, the position of the photodetector 30 may be configured to be adjustable relative to the living body Ob in a direction that intersects with the optical path Op2 of the signal light L2 at a predetermined angle, such as perpendicularly, for example.

[0199] With this configuration, the position of the photodetector 30 can be adjusted so that the center of the screen 30a of the photodetector 30 and the position where the laser light L1 is focused and irradiated onto the subject part Mp0 (laser light focusing area FA) roughly coincide or overlap in a direction perpendicular to the optical path Op2 of the photodetector 30.

[0200] In addition, the base 10 may be configured to be able to simultaneously adjust the first angle and the second angle by varying the angle of the main surface 10a with respect to the optical path of the laser light L1 within a plane defined by the optical path Op1 of the laser light L1 and the optical path Op2 from the subject area to the photodetector 30.

[0201] With this configuration, the incident angle A and the installation angle B with respect to the object part Mp0 can be simultaneously adjusted to match the shape of the individual living body Ob.

[0202] Furthermore, by varying the position of the photodetector 30 in a direction along the optical path Op2 of the signal light L2, the position of the photodetector 30 relative to the living body Ob in that direction can be adjusted, and the position of the photodetector 30 may be configured to be adjusted based on the concentration of substances in the blood so that the image of the signal light emitted from the vascular region Mp is transferred by the imaging lens 40 and formed on the light receiving surface of the photodetector.

[0203] With this configuration, the position of the photodetector 30 can be adjusted parallel to the optical path Op2 so that an image Im1 at a depth corresponding to the vascular region Mp in the subject part Mp0 is transferred to the screen 30a of the photodetector 30 as an image Im2 of equivalent size.

[0204] As a result, by using the imaging lens 40 to image the signal light L2 emitted from the laser light focusing area FA onto the screen 30a of the photodetector 30, the photodetector 30 can receive signal light with a sufficiently high intensity compared to the background light, thereby achieving a high S / N ratio and enabling high-precision measurements.

[0205] Second Embodiment A blood substance concentration measuring device 1A according to a second embodiment will be described with reference to the drawings.

[0206] (Configuration) In the above-mentioned embodiment 1, the base 10 is equipped with a rotating stage mechanism 11 and a height adjustment mechanism 12, and the angle and height of the base 10 are adjusted so that the vascular region Mp included in the subject part Mp0 of the living body Ob is restricted to a specified position and angle suitable for irradiation with the laser light L1.

[0207] FIG. 12 is a schematic diagram showing the state of the blood substance concentration measuring device 1A according to the second embodiment during measurement.

[0208] The blood substance concentration measuring device 1A (hereinafter sometimes referred to as "device 1A") according to embodiment 2 is configured to include a base 10, a light irradiation unit 20, a photodetector 30, an imaging lens 40, a measurement control unit 60A, a movable mechanism 71, a rotation stage mechanism 11, a position adjustment mechanism 12A, an imaging means 91A arranged in a normal direction to the main surface 10a of the base 10, and an imaging means 92A arranged in a direction parallel to the main surface 10a of the base 10.

[0209] The base 10 is provided with a position adjustment mechanism 12A that can vary the height ht in a direction perpendicular to the main surface 10a and change the position (X1A, Y1A) in a plane direction (X1-Y1 direction) parallel to the main surface 10a.

[0210] Furthermore, similar to the apparatus 1, the base 10 is mechanically coupled to a rotation stage mechanism 11 that changes the angle θC (see FIG. 3) of the main surface 10a with respect to the optical path Op1 of the laser light L1 and the optical path Op2 of the signal light L2 within the laser light incident plane. The rotation stage mechanism 11, for example, has a built-in motor and constitutes an angle changing mechanism that can reversibly rotate around a rotation axis CL parallel to the Y1 axis. The rotation axis CL may be configured to intersect with a spatial position where the test portion Mp0 is located.

[0211] The motor of the rotating stage mechanism 11 is driven by a control signal issued from the measurement control unit 60A, which operates the angle changing mechanism to rotate the base 10 connected to the rotating stage mechanism 11 around the rotation axis CL. This makes it possible to simultaneously adjust the incident angle A (see FIG. 3 ) of the laser light L1 irradiated from the light irradiation unit 20 onto the specimen Mp0 and the installation angle B (see FIG. 3 ) of the photodetector 30 relative to the specimen Mp0. As a result, the rotating stage mechanism 11 makes it possible to simultaneously set the incident angle A and the installation angle B to predetermined angles θA and θB (see FIG. 3 ), respectively.

[0212] The configurations of the light irradiator 20, photodetector 30, imaging lens 40, and movable mechanism 71 in the device 1A are the same as those in the device 1. Laser light L1 irradiated from the light irradiator 20 is irradiated onto a subject part Mp0 of a living body Ob, and signal light L2 reflected by the subject part Mp0 is received by the photodetector 30.

[0213] Also in the apparatus 1A, similarly to the apparatus 1, a movable mechanism 71 is connected to the photodetector 30, and the position of the photodetector 30 relative to the base 10 can be changed. That is, by operating the movable mechanism 71 based on a control signal from the measurement control unit 60A, the photodetector 30 can be reversibly moved in a direction parallel to the optical path Op2 of the signal light L2 from the laser light focusing area FA in the subject portion Mp0 to the photodetector 30. Similarly, the photodetector 30 can be reversibly moved in a direction perpendicular to the optical path Op2 of the signal light L2. Furthermore, the movable mechanism 71 may be configured to move the imaging lens 40 together with the photodetector 30.

[0214] The imaging means 91A and the imaging means 92A are imaging means that capture images of the living body Ob, for example, using a CCD (Charge Coupled Device) image sensor. The imaging means 91A is arranged facing the main surface 10a of the base 10 in the normal direction of the main surface 10a, and captures a planar image of the living body Ob placed on the main surface 10a. The imaging means 92 is arranged to the side of the main surface 10a of the base 10, facing the base 10, and captures a side image of the living body Ob placed on the main surface 10a. The image data captured by the imaging means 91A and the imaging means 92A is output to the measurement control unit 60A.

[0215] The measurement control unit 60A detects the image portion corresponding to the living body Ob from the received image, calculates the amount of positional deviation from the reference position where that image portion should be, and outputs a control signal to the position adjustment mechanism 12A to compensate for this.

[0216] Specifically, for example, when a height deviation in the height direction is detected based on an image from the imaging means 92A, the position adjustment mechanism 12A changes the height ht in the direction perpendicular to the main surface 10a based on the control signal to compensate for the height deviation of the living body Ob. Similarly, when a position deviation in the planar direction is detected based on an image from the imaging means 91A, the position adjustment mechanism 12A changes the position (X1A, Y1A) of the base 10 in the planar direction (X1-Y1 direction) of the main surface 10a based on the control signal to compensate for the position deviation in the planar direction of the living body Ob.

[0217] Alternatively, the amount of angular deviation from the reference angle that should be present can be calculated, a control signal to compensate for this can be output to the position adjustment mechanism 12A, and the base 10 connected by the rotation stage mechanism 11 can be rotated around the rotation axis CL to compensate for the deviation in angle θC.

[0218] Furthermore, when laser light L1 is irradiated from the light irradiation unit 20 onto the subject part Mp0 of the living body Ob, the imaging means 91A, 92A may detect the positions of the laser light concentration area FA and the subject part Mp0, respectively, using images detected and captured using a wavelength different from that of the laser light L1, and based on the detection results, the rotating stage mechanism 11 and the position adjustment mechanism 12A may be driven to perform position control so that the subject part Mp0 and the laser light concentration area FA roughly coincide with each other.

[0219] By detecting the position using the imaging means 91A and 92A, the object part Mp0 and the laser beam focusing area FA can be roughly aligned with high precision.

[0220] <Evaluation Test> Performance evaluation was carried out by an evaluation test using the example and comparative example of the device 1A. The results are described below.

[0221] (Example) A usable prototype was created and evaluated as an example of the device 1A. Fig. 13 is a schematic diagram showing an aspect of the example of the device 1A.

[0222] In the example of the device 1A, the light irradiator 20 uses a laser light source with a wavelength selected from the range of 2.5 μm to 12 μm, and the incident angle A is 65 degrees. The photodetector 30 uses near-infrared and mid-infrared sensors, and the installation angle B is 25 degrees. The imaging lens 40 has an f=25 mm and is installed approximately 50 mm from the laser light focusing area FA of the subject portion Mp0 and the light receiving surface 30a of the photodetector 30, respectively. The photodetector 30 is installed at the image transfer (focus) position of the laser light focusing area FA. Here, the detector focus depth is selected from 0.5 mm to 3.5 mm inside the skin of the living body Ob, and in this example, it is 1.5 mm.

[0223] 13, in the embodiment of the apparatus 1A, the base 10 is made of a rectangular parallelepiped member. On the main surface 10a of the base 10, on which the living body Ob, which is the subject, is placed, a guide member 122 is arranged for regulating the position (X1A, Y1A) of the living body Ob in a planar direction (X1-Y1 direction) parallel to the main surface 10a. The guide member 122 is configured to be installed after confirming its position from the normal direction of the main surface 10a, thereby ensuring the positional accuracy of the living body Ob in the planar direction parallel to the main surface 10a.

[0224] A support member 121 is arranged on the side of the base 10, and is configured to be reversibly slidable in a direction perpendicular to the main surface 10a of the base 10, and has a function of varying the height ht of the living body Ob in a direction perpendicular to the main surface 10a. In the embodiment of the device 1A, the function of the position adjustment mechanism 12A is realized by the guide member 122 and the holding member 121.

[0225] Next, the embodiment of the apparatus 1A includes a rotor 111 and a stator member 112 that constitute the rotation stage mechanism 11. Specifically, as shown in Fig. 13, a holding member 121 is arranged on a side surface of the base 10, and the rotor 112 is mechanically connected to the side surface of the holding member 121 on the further lateral side. The rotor 111 is rotatably held by the stator member 112 via a rotation axis CL that is parallel to the Y1 axis, and the rotor 111 is configured to be rotatable around the rotation axis CL. The rotation axis CL is arranged at a position that intersects with a subject portion Mp0 of a living body Ob placed on the main surface 10a of the base 10.

[0226] Furthermore, a lead screw 711 is inserted into the stator member 112 and stands upright from the base member 712 in a direction parallel to an optical path Op2 that runs from the laser light focusing area FA in the subject part Mp0 to the photodetector 30. When the lead screw 711 rotates, the stator member 112 and the base 10 connected thereto are configured to be reversibly movable linearly in a direction parallel to the optical path Op2.

[0227] The stator member 112 also includes a linear motion mechanism (not shown) that is reversibly slidable relative to the base member 712 in a direction perpendicular to the optical path Op2. The linear motion mechanism allows the base 10 connected to the stator member 112 to be reversibly moved in a direction perpendicular to the optical path Op2. As described above, in the embodiment of the device 1A, the function of the movable mechanism 71 is realized by the stator member 112, the lead screw 711, and the base member 712.

[0228] Next, in the embodiment of the device 1A, an imaging means 92A is provided in a direction parallel to the main surface 10a of the base 10. As shown in Fig. 13, the imaging means 92A may be disposed on a rotation axis CL that intersects with a spatial position corresponding to a subject portion Mp0 of a living body Ob placed on the main surface 10a of the base 10. When a height deviation in the height direction is detected based on an image from the imaging means 92A, the height ht of the base 10 in a direction perpendicular to the main surface 10a is changed to compensate for the height deviation of the living body Ob.

[0229] In this embodiment, the imaging means 91A for capturing an image of the living body Ob in a planar direction (X1-Y1 direction) parallel to the main surface 10a is omitted, and the function of regulating the position in the planar direction (X1A, Y1A) is realized by the guide member 121.

[0230] Comparative Example As a comparative example, the results of blood glucose level measurement by SMBG using a commercially available blood glucose level measuring device were used.

[0231] (Test Method) Using the dorsal surface of the index finger of an adult male subject as the test object, blood glucose measurements were performed at approximately regular intervals from 12:00 to 21:30 using the Example using the device 1A and the Comparative Example using SMBG. In the measurement using the device 1A, the living body Ob was placed on the main surface of the base, and measurements were performed simultaneously for the Example and Comparative Example.

[0232] (Test Results) Figure 14 shows the results of a blood substance concentration measurement test using the example of device 1A and a comparative example using SMBG. As shown in Figure 14, the measured values ​​of the example were within ±5% of the measured values ​​of the comparative example at the same time, and it can be seen that they are in good agreement with the comparative example, which is a commercially available product that represents the current standard. This confirms that device 1A can suppress changes in measurement results due to differences in how the measurement site is placed on the device, and can perform highly accurate measurements stably.

[0233] <Summary> As explained above, the blood substance concentration measuring device 1A according to the second embodiment further includes, in the configuration according to the first embodiment, an imaging unit 91A and an imaging unit 92A that capture an image including a living body Ob, and the measurement control unit 60A detects an image portion corresponding to the living body Ob from the acquired image and calculates the amount of positional deviation from a reference position where the image portion should be, and the base 10 may be configured to be able to change the height in the vertical direction of the main surface 10a so as to compensate for the amount of positional deviation.

[0234] With this configuration, the imaging means 91A and the imaging means 92A can easily adjust the positional relationship of the living body Ob with respect to the light irradiation unit 20 to match the shape of the individual living body Ob so that laser light is focused and irradiated onto the vascular region Mp located inside the epidermis in the subject part Mp0.

[0235] In addition, the measurement control unit 60A calculates the amount of angular deviation from the reference angle at which the image portion corresponding to the living body Ob should be located from the acquired image, and the base 10 may be configured to be able to change the angle of the main surface 10a relative to the optical path Op1 of the laser light L1 so as to compensate for the amount of angular deviation calculated based on the acquired image within a plane defined by the optical path Op1 of the laser light L1 and the optical path Op2 from the subject portion to the photodetector 30.

[0236] This configuration allows the incident angle A and installation angle B with respect to the subject portion Mp0 to be simultaneously and easily adjusted to match the shape of the individual living body Ob. As a result, the subject can more easily measure the concentration of a substance in their blood without being concerned about how to place the measurement site on the device or the angle of incidence of the laser or the installation angle of the detector.

[0237] Embodiment 3 A blood substance concentration measuring device 1B according to embodiment 3 will be described with reference to the drawings. In the above example, the measurement is performed with the back side of the finger as the subject part Mp0, with the palm surface of the finger as the living body Ob being in contact with the base 10. However, instead of the finger as the living body Ob, another part of the body may be used as the subject part for measurement.

[0238] FIG. 13 is a schematic diagram showing the state of blood substance concentration measuring device 1B according to embodiment 3 during measurement. Blood substance concentration measuring device 1B (hereinafter sometimes referred to as "device 1B") is configured to perform measurement by irradiating laser light onto the forehead instead of a finger as the living body Ob, and does not have a base 10 on which the living body Ob is placed. Device 1B uses imaging means 91A, 92A to detect the positions of the subject part Mp0 and the laser light focusing area FA, and performs measurement by controlling the focusing position of the laser light based on the detection results so that the subject part Mp0 and the laser light focusing area FA roughly coincide. This configuration makes it possible to measure blood substance concentrations more easily.

[0239] The device 1B according to the third embodiment may be configured to measure another part of the body other than the forehead, that is, an exposed part of the skin, as the subject part Mp0 to be measured.

[0240] In the device 1B, similarly to the device 1, laser light L1 emitted from the light irradiating unit 20 is irradiated onto the subject part Mp0 of the living body Ob, and signal light L2 reflected by the subject part Mp0 is received by the photodetector 30. The configurations of the light irradiating unit 20, the photodetector 30, the imaging lens 40, and the movable mechanism 71 in the device 1B are the same as those of the device 1 in the first and second embodiments.

[0241] (Light irradiation angle adjustment mechanism 93B) The device 1B includes a light irradiation angle adjustment mechanism 93B, which is a structural member that holds the light irradiation unit 20 and the photodetector 30 via the movable mechanism 71, between the light irradiation unit 20 and the photodetector 30. This light irradiation angle adjustment mechanism 93B has a function of defining the positions and angles of the photodetector 30 and the light irradiation unit 20 so that the optical path Op1 of the laser light L1 and the optical path Op2 of the signal light L2 intersect at a predetermined position.

[0242] The light irradiation angle adjustment mechanism 93B has a motor built in and an angle changing mechanism that can reversibly rotate around a rotation axis CL parallel to the Y1 axis. The rotation axis CL may be configured to intersect with the spatial position where the subject part Mp0 is located in three-dimensional space. By rotating the light irradiation angle adjustment mechanism 93B, the angles of the optical path Op1 of the laser light L1 and the optical path Op2 of the signal light L2 relative to the skin surface of the living body Ob can be changed within the laser light incident plane.

[0243] Specifically, the laser beam irradiation angle adjustment mechanism 93B operates an angle change mechanism by driving a motor in response to a control signal issued from the measurement control unit 60B. The light irradiator 20 and the photodetector 30 held by the laser beam irradiation angle adjustment mechanism 93B are then rotated around the rotation axis CL. This allows simultaneous adjustment of the incident angle A of the laser beam L1 irradiated from the light irradiator 20 onto the test part Mp0 and the installation angle B of the photodetector 30 relative to the test part Mp0. As a result, the laser beam irradiation angle adjustment mechanism 93B allows the incident angle A and the installation angle B to be simultaneously set to predetermined angles θA and θB, respectively.

[0244] (Position Adjustment Mechanism 94B) A position adjustment mechanism 94B that changes the position of the light irradiation angle adjustment mechanism 93B within the laser light incident plane is connected to the light irradiation angle adjustment mechanism 93B. The position adjustment mechanism 94B operates the position adjustment mechanism 94B in response to a control signal from the measurement control unit 60B to move the light irradiation angle adjustment mechanism 93B within the laser light incident plane, thereby moving the intersection of the optical path Op1 of the laser light L1 and the optical path Op2 of the signal light L2 relative to the skin surface of the living body Ob to a position that should be the test part Mp0 of the living body Ob.

[0245] Similarly to the apparatus 1, a movable mechanism 71 is interposed between the photodetector 30 and the light irradiation angle adjustment mechanism 93B, and is configured to change the position of the photodetector 30 relative to the light irradiation angle adjustment mechanism 93B. That is, by operating the movable mechanism 71 based on a control signal from the measurement control unit 60B, the photodetector 30 can be reversibly moved in directions parallel to and perpendicular to the optical path Op2 of the signal light L2 from the subject portion Mp0 to the photodetector 30. The movable mechanism 71 may be, for example, a linear motion mechanism using a lead screw or a MEMS actuator using a piezoelectric element. The movable mechanism 71 may also be configured to move the imaging lens 40 together with the photodetector 30.

[0246] (Imaging Units 91A, 92A) The device 1B includes an imaging unit 91A arranged in a normal direction to the skin surface near the subject part Mp0 of the living body Ob, and an imaging unit 92A arranged in a direction parallel to the skin surface.

[0247] The imaging means 91A and the imaging means 92A are imaging means for capturing images of the living body Ob. The imaging means 91A is arranged facing the test part Mp0 in the normal direction of the skin surface of the living body Ob, captures a planar image of the skin surface of the living body Ob, and outputs the image data to the measurement control unit 60B. The imaging means 92A is arranged to the side of the skin surface of the living body Ob, facing the test part Mp0, captures an image of the living body Ob viewed from the side, and outputs the image data to the measurement control unit 60B.

[0248] The measurement control unit 60B detects the image portion corresponding to the living body Ob from the received image, calculates the positional deviation of that image portion from the reference position where it should be, and outputs a control signal to the position adjustment mechanism 94B to compensate for this positional deviation.

[0249] Specifically, for example, when a height deviation in the height direction is detected based on an image from the imaging means 92A, the position adjustment mechanism 94B changes the height ht in the direction perpendicular to the skin surface of the living body Ob based on the control signal to compensate for the height deviation of the living body Ob. Similarly, when a position deviation in the planar direction is detected based on an image from the imaging means 91A, the position adjustment mechanism 94B changes the positions X1A, Y1A of the light irradiation angle adjustment mechanism 93B in the direction parallel to the skin surface of the living body Ob (X1-Y1 direction) based on the control signal to compensate for the position deviation in the planar direction of the light irradiation unit 20 and the photodetector 30.

[0250] Furthermore, a configuration may be adopted in which, when the laser light L1 is irradiated from the light irradiating unit 20 onto the subject part Mp0 of the living body Ob, the positions of the laser light condensing area FA and the subject part Mp0 are detected by the imaging means 91A, 92A, and based on the detection results, the position adjustment mechanism 94B and / or the irradiation angle adjustment mechanism 93B are driven to perform position control so that the subject part Mp0 and the laser light condensing area FA generally coincide with each other. With such a configuration, the subject can more easily measure the concentration of a substance in their blood without being concerned about how the measurement site is placed on the device or the angle of incidence of the laser or the installation angle of the detector.

[0251] <Summary> As explained above, the blood substance concentration measuring device 1B according to the third embodiment may be configured in the same manner as the second embodiment, further including a light irradiation angle adjustment mechanism 93B that holds the light irradiation unit 20 and the photodetector 30 and that, by rotation, changes the angle of the optical path Op2 of the laser light L1 and the signal light L2 relative to the skin surface of the living body Ob within the laser light incident plane.

[0252] With this configuration, the incident angle A of the laser light L1 irradiated from the light irradiation unit 20 onto the test part Mp0 and the installation angle B of the photodetector 30 relative to the test part Mp0 can be simultaneously adjusted, and the positions and angles of the photodetector 30 and the light irradiation unit 20 can be determined so that the optical path Op1 of the laser light L1 and the optical path Op2 of the signal light L2 intersect at a predetermined position.

[0253] Furthermore, the configuration may further include a position adjustment mechanism 94B that changes the position of the light irradiation angle adjustment mechanism 93B within the laser light incident plane. With this configuration, the intersection of the optical path Op1 of the laser light L1 and the optical path Op2 of the signal light L2 relative to the skin surface of the living body Ob can be moved to a position that should be the test part Mp0 of the living body Ob.

[0254] With this configuration, the subject can more easily measure the concentration of a substance in the blood without being concerned about how to place the measurement site on the device or the angle at which the laser is incident or the detector is installed.

[0255] While specific configurations of the present disclosure have been described above using exemplary embodiments, the present disclosure is not limited to the above-described embodiments except for its 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 the embodiments within the scope of the present invention.

[0256] (1) In the above embodiment, glucose is used as an example of a measurement target substance (first blood substance) 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 those described above. By varying the wavelength of the laser light L1 emitted by the light irradiating unit 20 depending on the type of blood component, the device can be widely used for detecting other detection targets.

[0257] For example, the wavelength of the laser light L1 emitted by the light irradiator 20 may be 8.23±0.05 μm (8.18 μm or more and 8.28 μm or less), and the blood component may be 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 in the range of −0.05 μm or more and +0.05 μm or less. Experiments by the inventors have confirmed that the lactate concentration measured by a photodetector when the wavelength of light emitted by the light irradiator 20 is 8.23 ​​μm generally correlates with the lactate level measurement results from a self-drawn blood sample.

[0258] (2) In the above embodiment, hemoglobin is used as an example of the reference substance (second blood substance) to be detected in the reference measurement. However, the reference substance according to the present disclosure is not limited to the above, and can be used for other reference substances by varying the wavelength of the laser light L1 emitted by the light irradiator 20 depending on the type of blood component used as the reference substance.

[0259] (3) In the above embodiment, the wavelength of the oscillated laser light L1 can be switched and adjusted by adjusting the type and matching conditions of the nonlinear optical crystal 223 in the optical parametric oscillator 22.

[0260] However, the light irradiating unit 20 may be configured to selectively use multiple optical parametric oscillators 22 and selectively irradiate laser light L1 of multiple wavelengths, thereby making it possible to measure multiple types of blood components.The light emitted from the light source 21 may be switched to enter multiple optical parametric oscillators emitting light of different wavelengths, and each optical parametric oscillator may selectively emit light of a different wavelength, allowing reference measurement and main measurement of the measurement target to be selectively performed using each wavelength.

[0261] Alternatively, a configuration may be adopted in which a plurality of light irradiating units 20 emitting light of different wavelengths are used, and light from two of the light irradiating units 20 is selectively emitted as laser light L1 using an optical coupler, mirror, etc. In this case, unlike a configuration employing an optical system in which the width or thickness of the optical path varies depending on the wavelength of light, for example, an optical system for a plurality of blood components can share an optical system consisting of a condenser lens 50, a base 10, an imaging lens 40, and a photodetector 30 capable of detecting mid-infrared light.

[0262] (4) In the above embodiment, the light irradiation unit 20 is configured such that the first laser light for object measurement and the second laser light for reference measurement have different wavelengths. However, as long as the first laser light for object measurement is absorbed by the measurement target substance and the second laser light for reference measurement is absorbed by the reference substance, the first laser light and the second laser light may be configured to have different irradiation conditions other than wavelength. For example, the first laser light and the second laser light may have different intensities of light emitted from the irradiation unit.

[0263] (5) In the above embodiment, the measurement target substance and the reference substance are different blood substances. However, the reference measurement may be performed using the same substance as the measurement target substance.

[0264] (6) In the above embodiment, the blood substance concentration measuring device is exemplified by an optical system including an imaging lens 40 between the subject Mp0 and the photodetector 30. However, the blood substance concentration measuring device according to the present disclosure may be configured to image the signal light L2 reflected from the vascular region Mp of the living body Ob on the photodetector 30, and the light receiving optical system may be modified as appropriate. For example, a configuration using multiple lenses or a configuration with a mirror disposed midway along the optical path may be used.

[0265] (7) The order in which steps are performed in the embodiments is merely an example for specifically explaining the present invention, and other orders may be used. Also, some of the steps may be performed simultaneously (in parallel) with other steps.

[0266] Furthermore, at least some of the functions of the embodiments and their modifications may be combined.

[0267] <<Supplementary Information>> The above-described embodiments each illustrate a preferred specific example of the present invention. The numerical values, shapes, materials, components, component placement and connection configurations, steps, and step order shown in the embodiments are merely examples and are not intended to limit the present invention. Furthermore, among the components in the embodiments, those not recited in the independent claims that represent the highest concept of the present invention are described as optional components that constitute more preferred embodiments.

[0268] The order in which the above methods are performed is merely an example for specifically explaining the present invention, and other orders may be used. Also, some of the above methods may be performed simultaneously (in parallel) with other methods.

[0269] In order to facilitate understanding of the invention, the scale of the components in the drawings of the above embodiments may differ from the actual scale. Furthermore, the present invention is not limited to the description of the above embodiments, and can be modified as appropriate within the scope of the gist of the present invention.

[0270] Furthermore, all the numbers used above are merely examples for the purpose of specifically explaining the present invention, and the present invention is not limited to the numbers used as examples.

[0271] A blood substance concentration measuring device, a blood substance concentration measuring method, and a program according to one embodiment of the present disclosure can be widely used as medical equipment for measuring blood substance conditions such as blood glucose levels and blood lipid levels on a daily basis in the prevention and treatment of lifestyle-related diseases.

[0272] 1, 1A, 1B Blood substance concentration measuring device 10 Base 11 Rotating stage mechanism 12 Height adjustment mechanism 12A Position adjustment mechanism 20 Light irradiation unit 21 Light source 22 Optical parametric oscillator 221 Incident side semi-transparent mirror 222 Exit side semi-transparent mirror 223 Nonlinear optical crystal 30 Photodetector 30a Screen (light receiving surface) 40 Imaging lens (first lens) 50 Condenser lens (second lens) 60, 60A, 60B Measurement control unit 70 Photodetection unit 71 Movable mechanism 711 First linear transport mechanism 712 Second linear transport mechanism 80 Aperture 80a Opening 91A Imaging means 92A Imaging means 93B Light irradiation angle adjustment mechanism 94B Position adjustment mechanism

Claims

1. A blood substance concentration measuring device that measures the concentration of blood substances contained in the blood of a subject in a living organism, A base on which the living organism can be placed, A light irradiation unit that focuses and irradiates laser light from the main surface side of the base onto the skin surface of the living body on the side opposite to the main surface and onto a specific region in the subject area located in the skin on the opposite side of the living body, On the main surface side of the base, a photodetector is provided to receive reflected light based on the laser light, which is signal light in which the intensity of some wavelengths of light from the laser light has been weakened, and to detect its intensity. An imaging lens is positioned between the subject area and the photodetector, such that an image of the signal light emitted from the laser light focusing region in the subject area can be formed on the photodetector. The system includes a measurement and control unit that measures the concentration of the blood substance in the laser light focusing region based on the intensity of the signal light, The first angle between the normal to the skin surface of the subject and the optical path of the laser light is different from the second angle between the normal and the optical path of the signal light from the laser light focusing region to the photodetector. The position of the living organism relative to the light irradiation area is defined such that the vascular region located inward from the epidermis in the subject area overlaps with the laser light focusing region. The position of the photodetector relative to the living organism is defined such that the image of the signal light emitted from the vascular region overlapping the laser light focusing region is transferred by the imaging lens and imaged onto the light-receiving surface of the photodetector. Blood substance concentration measuring device.

2. The base is configured to allow adjustment of the position of the living organism relative to the light irradiation area by varying the height of the main surface in the vertical direction. A blood substance concentration measuring device according to claim 1.

3. The position of the photodetector relative to the living organism in a given direction can be adjusted by changing the position of the photodetector in a direction that intersects with the optical path of the signal light. A blood substance concentration measuring device according to claim 1.

4. The base is configured to allow simultaneous adjustment of the first angle and the second angle by varying the angle of the main surface with respect to the optical path of the laser light within the plane determined by the optical path of the laser light and the optical path from the subject to the photodetector. A blood substance concentration measuring device according to claim 1.

5. The position of the photodetector relative to the living organism in a given direction can be adjusted by varying the position of the photodetector in a direction along the optical path of the signal light. The position of the photodetector is adjusted based on the concentration of the blood substance so that the image of the signal light emitted from the blood vessel region is transferred by the imaging lens and formed on the light-receiving surface of the photodetector. A blood substance concentration measuring device according to claim 1.

6. The light irradiation unit is configured to selectively irradiate a first laser beam for target measurement that is absorbed by a first blood substance which is the substance to be measured, and a second laser beam for reference measurement that is absorbed by a second blood substance which is the reference substance. In the reference measurement, the absorption rate of the second laser light absorbed by the second blood substance is greater than the absorption rate of the first laser light absorbed by the first blood substance in the target measurement. A blood substance concentration measuring device according to any one of claims 1 to 5.

7. The reference substance exhibits higher concentration stability in the blood than the substance being measured. A blood substance concentration measuring device according to claim 6.

8. The measurement control unit measures the concentration of the second blood substance when the specific region is included in the vascular region of the subject, based on the irradiation of the second laser light. Based on the irradiation of the first laser light, the system is configured to measure the concentration of the first blood substance in the specific region as the concentration of the first blood substance in the measurement target portion. A blood substance concentration measuring device according to claim 6.

9. The optical path of the laser beam is equipped with a focusing lens located between the light irradiation unit and the subject unit, which focuses the laser beam into the irradiation area. A blood substance concentration measuring device according to claim 1.

10. In the optical path from the subject to the photodetector, in the section from the surface of the biological tissue to the photodetector, the signal light propagates through space except for the section passing through the imaging lens. In the optical path from the light irradiation unit to the subject unit, in the section from the light irradiation unit to the surface of the biological tissue, the laser light propagates through space except for the section through which it passes the focusing lens. A blood substance concentration measuring device according to claim 9.

11. Furthermore, the system includes imaging means for capturing images including the living organism, The measurement control unit detects the image portion corresponding to the living body from the acquired image and calculates the amount of positional deviation of the image portion from the reference position where it should originally be. The base is adjustable in height in the vertical direction of the main surface to compensate for the amount of misalignment. A blood substance concentration measuring device according to any one of claims 1 to 5 or 9.

12. Furthermore, the system includes imaging means for capturing images including the living organism, The measurement control unit detects the image portion corresponding to the living body from the acquired image and calculates the amount of angular deviation of that image portion from the reference angle where it should originally be. The base is capable of changing the angle of the main surface with respect to the optical path of the laser beam in order to compensate for the amount of angular misalignment. A blood substance concentration measuring device according to any one of claims 1 to 5 or 9.

13. Furthermore, it is equipped with a light irradiation angle adjustment mechanism that holds the light irradiation unit and the photodetector, and rotates to change the angle of the optical path of the laser light and signal light relative to the skin surface of the living organism within the laser light incident plane. A blood substance concentration measuring device according to claim 1.

14. Furthermore, the system is further equipped with a position adjustment mechanism that allows the position of the light irradiation angle adjustment mechanism within the laser light incident plane to be varied. A blood substance concentration measuring device according to claim 13.

15. A method for measuring the concentration of blood substances contained in the blood of a subject in a living organism, The living organism is placed on the main surface of the base, and from the main surface side of the base, a laser beam for target measurement, which is absorbed by the blood substance to be measured, is focused and irradiated by the light irradiation unit onto the skin surface of the living organism on the side opposite the main surface and a specific area of ​​the subject in the skin located on the opposite side of the living organism. On the main surface side of the base, using an imaging lens positioned between the subject and the photodetector, an image of the reflected light of the laser, which is emitted from the laser light focusing region in the subject and in which the intensity of some wavelengths of light from the laser light is weakened, is formed on the photodetector. The photodetector receives the signal light and measures its intensity as the concentration of the blood substance in the specific region. The first angle between the normal to the skin surface of the subject and the optical path of the laser light is different from the second angle between the normal and the optical path of the signal light from the specific region to the photodetector. The position of the living organism relative to the light irradiation area is defined such that the vascular region located inward from the epidermis in the subject area overlaps with the laser light focusing region. The position of the photodetector relative to the living organism is defined such that the image of the signal light emitted from the vascular region overlapping the laser light focusing region is transferred by the imaging lens and formed on the light-receiving surface of the photodetector. Blood substance concentration measurement method.

16. Prior to the measurement, the position of the living organism relative to the light irradiation area is adjusted by making the height of the base different from that of the main surface. The method for measuring blood substance concentration according to claim 15.

17. Prior to the measurement, the position of the photodetector is changed in a direction that intersects with the optical path of the signal light, thereby adjusting the position of the photodetector relative to the living organism in that direction. The method for measuring blood substance concentration according to claim 15.

18. Prior to the aforementioned target measurement, a reference measurement is performed to measure the concentration of the blood substance in a specific region by varying the angle of the main surface within the plane determined by the optical path of the laser light and the optical path from the subject to the photodetector, thereby simultaneously adjusting the first angle and the second angle based on the concentration of the blood substance. The method for measuring blood substance concentration according to claim 15.

19. Prior to the aforementioned target measurement, the position of the photodetector relative to the living body in that direction is adjusted by performing a reference measurement to measure the concentration of the blood substance by varying the position of the photodetector along the optical path of the signal light. In this adjustment, the position of the photodetector is adjusted based on the concentration of the blood substance so that the image of the signal light emitted from the blood vessel region is transferred by the imaging lens and formed on the light-receiving surface of the photodetector. The method for measuring blood substance concentration according to claim 15.

20. When the laser light is referred to as the first laser light, the blood substance as the first blood substance, and the concentration of the blood substance as the concentration of the first blood substance, In the aforementioned reference measurement, A second laser beam for reference measurement, which is absorbed by a second blood substance that is a reference substance, is irradiated from the light irradiation unit to the irradiation area. Using the imaging lens, the signal light of the second laser beam reflected from the specific region is imaged onto the photodetector. The photodetector receives the signal light of the second laser beam, and the concentration of the second blood substance based on the signal light is measured as the concentration of the second blood substance in the measurement target area. The absorption rate of the second laser light by the second blood substance is greater than the absorption rate of the first laser light by the first blood substance in the aforementioned measurement. A method for measuring the concentration of a substance in the blood according to any one of claims 15 to 19.

21. The reference substance exhibits higher concentration stability in the blood than the substance being measured. The method for measuring blood substance concentration according to claim 20.

22. Based on the irradiation of the second laser light, the concentration of the second blood substance is measured when the specific region is included in the vascular region of the subject. Based on the irradiation of the first laser light, the concentration of the first blood substance in the specific region is measured as the concentration of the first blood substance in the measurement target portion. The method for measuring blood substance concentration according to claim 20.

23. A program that causes a computer to perform a blood substance concentration measurement process to measure the concentration of blood substances contained in the blood of a subject in a living organism, The blood substance concentration measurement process described above is: The living organism is placed on the main surface of the base, and from the main surface side of the base, a laser beam for target measurement, which is absorbed by the blood substance to be measured, is focused and irradiated by the light irradiation unit onto the skin surface of the living organism on the side opposite the main surface and a specific area of ​​the subject in the skin located on the opposite side of the living organism. On the main surface side of the base, using an imaging lens positioned between the subject and the photodetector, an image of the reflected light of the laser, which is emitted from the laser light focusing region in the subject and in which the intensity of some wavelengths of light from the laser light is weakened, is formed on the photodetector. The photodetector receives the signal light and measures its intensity as the concentration of the blood substance in the specific region. The first angle between the normal to the skin surface of the subject and the optical path of the laser light is different from the second angle between the normal and the optical path of the signal light from the specific region to the photodetector. The position of the living organism relative to the light irradiation area is defined such that the vascular region located inward from the epidermis in the subject area overlaps with the laser light focusing region. The position of the photodetector relative to the living organism is defined such that the image of the signal light emitted from the vascular region overlapping the laser light focusing region is transferred by the imaging lens and formed on the light-receiving surface of the photodetector. program.

Images