JP5652599B2 - Concentration determination apparatus, concentration determination method and program - Google Patents

Description

  Some embodiments of the present invention relate to a concentration quantification apparatus, a concentration quantification method, and a program for quantifying the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers.

  Conventionally, the blood sugar level has been measured by collecting blood from a fingertip or the like and measuring the enzyme activity for glucose in the blood. However, such a blood glucose level measurement method requires blood sampling from a fingertip or the like, and is troublesome and painful in blood sampling, or requires a measurement chip to attach blood. There is a demand for a non-invasive blood glucose level measurement method that does not require a blood pressure.

  Then, the method of irradiating near infrared light to skin and calculating | requiring the density | concentration of glucose from the light absorption amount is examined (for example, refer patent document 1). Specifically, a calibration curve indicating the relationship between the glucose concentration, the wavelength of light to be irradiated, and the amount of light absorbed is prepared in advance, a certain wavelength range is scanned using a monochromator, etc. The amount of absorption with respect to the wavelength is obtained, and the glucose concentration is calculated by comparing the wavelength and the amount of absorption with a calibration curve.

Japanese Patent No. 3931638

However, since the conventional non-invasive blood glucose level measurement method measures the near-infrared absorption spectrum of the dermis layer by determining the distance between light input and output, the measured absorption spectrum includes not only the absorption spectrum of the dermis layer. The absorption spectrum of the epidermis layer and the subcutaneous tissue layer is also included, and there is a problem that the observed change in the absorption coefficient includes noise due to the epidermis layer and the subcutaneous tissue layer.
The present invention has been made in view of the above points, and an object thereof is to provide a concentration quantification apparatus, a concentration quantification method, and a program that reduce the influence of noise caused by layers other than the target layer.

Some aspects of the present invention have been made in order to solve the above-described problems. Among the observation targets formed from a plurality of layers, the concentration for quantifying the concentration of a biological component that is a target component in an arbitrary layer Among the plurality of light receiving units, the quantification device, the irradiation unit for irradiating the observation target with light, the light receiving unit having a plurality of light receiving units for receiving the light backscattered by the observation target, and the plurality of light receiving units A selecting unit that identifies and selects a light receiving unit that receives the light by an arbitrary layer, a light intensity obtaining unit that acquires an intensity of light received by the identified light receiving unit, and the specified from the irradiation unit An optical path length distribution storage unit for storing a propagation path length distribution model in the plurality of layers on the light propagation path to the light receiving unit, and a time-resolved waveform model of the light received by the specified light receiving unit are described. Time-resolved waveform storage means, optical path length acquisition means for acquiring optical path lengths of the plurality of layers at a predetermined time of the propagation optical path length distribution model from the optical path length distribution storage means, and the light intensity acquisition means The light absorption coefficient calculating means for calculating the light absorption coefficient of the arbitrary layer based on the light intensity acquired by the optical path length acquiring means and the optical path length of the plurality of layers acquired by the optical path length acquiring means, and the light absorption coefficient calculating means And a concentration calculating means for calculating the concentration of the biological component in the arbitrary layer based on the light absorption coefficient calculated by.
Specifically, it is a concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers, and irradiates the observation target with short-time pulsed light. An irradiating means, a light receiving means having a plurality of light receiving parts for receiving the light back-scattered by the observation target, and the short time pulse light among the plurality of light receiving parts by the arbitrary layer A selection unit that selects a specific light receiving unit that receives backscattered light, and an intensity of light received by the specific light receiving unit at a predetermined time after the time when the irradiation unit irradiates pulse light for a short time. A light intensity acquisition unit, and a plurality of light scattering medium layers disposed on a propagation path of light from the irradiation unit to the specific light receiving unit of the short-time pulse light irradiated to the observation target. Layer Optical path length distribution storage means for storing a model of propagation optical path length distribution, and time-resolved waveform storage for storing a model of time-resolved waveform of short-time pulsed light irradiated on the observation target and received by the specific light receiving unit And an optical path length acquisition unit that acquires an optical path length of each of the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage unit; Light intensity model acquisition means for acquiring the light intensity at the predetermined time of the model of the time-resolved waveform of the short-time pulsed light from the time-resolved waveform storage means; the light intensity acquired by the light intensity acquisition means and the optical path Based on the optical path length of each of the layers of the plurality of light scattering media acquired by the length acquisition unit and the light intensity model acquired by the light intensity model acquisition unit, the light absorption coefficient of the arbitrary layer is calculated. A light-absorbing coefficient calculating unit that emits light; and a concentration calculating unit that calculates the concentration of the target component in the arbitrary layer based on the light-absorbing coefficient calculated by the light-absorbing coefficient calculating unit. .
Thereby, the light absorption count of an arbitrary layer can be selectively calculated from the time-resolved waveform of the received light. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.
Here, short-time pulsed light means pulsed light having a pulse width of about 10 psec or less. As the short-time pulse light, pulse light having a pulse width in the range of 0.1 psec to 10 psec may be used.

In some embodiments of the present invention, the light intensity acquisition unit acquires light intensities at a plurality of times t _{1 to} t _{m that} are equal to or more than the number n of the observation target layers, and the light absorption coefficient calculation unit. Is characterized in that the light absorption coefficient of an arbitrary layer is calculated based on the following formula (1).

Where ln (A) represents the natural logarithm of A, I (t) represents the light intensity received by the light receiving means at time t, and N (t) represents the time-resolved waveform of the short-time pulsed light. L _i (t) represents the optical path length of the i-th layer at time t of the model of the propagation optical path length distribution, and μ _i represents the light absorption coefficient of the i-th layer. Show.

  In some embodiments of the present invention, the irradiating unit irradiates light having a plurality of wavelengths 1 to q, and the light absorption coefficient calculating unit irradiates the light absorption coefficient in the arbitrary layer. The concentration calculation means calculates the concentration of the target component in the arbitrary layer based on the following formula (2).

Here, μ _{a (i)} represents the light absorption coefficient of the wavelength i in the a-th layer which is the arbitrary layer, g _j represents the molar concentration of the j-th component forming the observation target, and ε _{j ( i)} represents the light absorption coefficient for the wavelength i of the j-th component, p represents the number of main components forming the observation object, and q represents the number of types of wavelengths irradiated by the irradiation means.

  Further, in some aspects of the present invention, a position at which the observation target is irradiated with the short-time pulse light from the irradiation unit is an irradiation position, and light in which the short-time pulse light is backscattered by the observation target is from the observation target. The light receiving means has a plurality of light receiving portions having different irradiation light receiving intervals, where the light exiting position is a light receiving position, and the interval between the irradiation position and the light receiving position is an irradiation light receiving interval. The selection means is configured to provide an irradiation / reception interval in which the short-time pulse light can propagate to the arbitrary layer based on a depth of arrival of the short-time pulse light into the observation target determined according to the irradiation / reception interval. The light receiving unit having the above is selected.

  Further, in some embodiments of the present invention, the irradiation unit includes an irradiation optical fiber that transmits short-time pulse light to the surface of the observation target, and the light receiving unit receives light backscattered by the observation target. A light receiving optical fiber for transmission, and the irradiation optical fiber and the light receiving optical fiber are mounted on a probe device that fixes a center interval between the optical fiber cores by a predetermined irradiation light receiving interval; The irradiation object is irradiated with a short time pulse by bringing the tip of the irradiation optical fiber and the tip of the light receiving optical fiber exposed at the tip of the light into contact with the surface of the observation object. The light receiving process of the light which pulsed light was backscattered by the said observation object is performed.

  Further, according to some aspects of the present invention, the light receiving unit includes a plurality of light receiving optical fibers arranged at equal irradiation light receiving intervals.

  Further, according to some aspects of the present invention, the light receiving unit includes a light condensing element that condenses light transmitted by a plurality of light receiving optical fibers arranged at equal irradiation light receiving intervals on the same light receiving surface. It is characterized by.

  Further, according to some aspects of the present invention, the irradiation optical fiber and the light receiving optical fiber are dispersion-compensated single mode optical fibers that compensate for wavelength dispersion of the plurality of wavelengths 1 to q irradiated by the irradiation unit. It is characterized by being.

  Further, according to some aspects of the present invention, the irradiation optical fiber and the light receiving optical fiber have a group delay time difference associated with wavelength dispersion of the light of the plurality of wavelengths 1 to q irradiated by the irradiation unit. It is characterized by being shorter than the propagation time corresponding to the peak of the propagation optical path length distribution of the layer on the most surface side among the light scattering medium layers.

Further, some aspects of the present invention include an irradiation unit that irradiates light to an observation target formed from a plurality of layers, and a light receiving unit that includes a plurality of light receiving units that receive the light backscattered by the observation target. And a selecting unit that identifies and selects a light receiving unit that receives the light by the arbitrary layer among the plurality of light receiving units, and a light propagation path from the irradiation unit to the specified light receiving unit. An optical path length distribution storage unit that stores a model of a propagation optical path length distribution in the plurality of layers, and a time-resolved waveform storage unit that stores a model of a time-resolved waveform of the light received by the specified light receiving unit, A concentration quantification method using a concentration quantification apparatus for quantifying a concentration of a biological component that is a target component in an arbitrary layer of the observation target, wherein the light intensity acquisition means receives the light received by the identified light receiving unit The optical path length acquisition unit acquires the optical path lengths of the plurality of layers at a predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage unit, and the light absorption coefficient calculation unit includes: Based on the light intensity acquired by the light intensity acquisition unit and the optical path lengths of the plurality of layers acquired by the optical path length acquisition unit, a light absorption coefficient of the arbitrary layer is calculated, and the concentration calculation unit includes the light The concentration of the biological component in the arbitrary layer is calculated based on the light absorption coefficient calculated by the absorption coefficient calculation means.
Specifically, an irradiating means for irradiating an observation target formed of a plurality of light scattering medium layers with a short-time pulse light, and a plurality of light receiving the light back-scattered by the observation target by the short-time pulse light A light receiving means having a plurality of light receiving parts, a selection means for selecting a specific light receiving part for receiving the light back-scattered by the arbitrary layer from the plurality of light receiving parts, and the observation target Stores a model of propagation optical path length distribution in each of a plurality of light scattering medium layers arranged on a light propagation path from the irradiating means to the specific light receiving portion of the short-time pulse light to be irradiated Optical path length distribution storage means, and time-resolved waveform storage means for storing a model of a time-resolved waveform of short-time pulsed light that is irradiated to the observation object and received by the specific light receiving unit. A concentration quantification method using a concentration quantification device for quantifying the concentration of a target component in an arbitrary layer, wherein the light intensity acquisition means is a predetermined time after the time when the irradiation means irradiates pulse light for a short time. The light receiving unit obtains the intensity of light received by the specific light receiving unit, and the optical path length acquisition unit is configured to transmit, from the optical path length distribution storage unit, the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution. The light intensity model acquisition means acquires the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage means, The light absorption coefficient calculating means acquires the light intensity acquired by the light intensity acquiring means, the optical path length of each layer of the plurality of light scattering media acquired by the optical path length acquiring means, and the light intensity model acquiring means. Light A light absorption coefficient of the arbitrary layer based on the degree model, and the concentration calculating means calculates the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means. Is calculated.

Further, some aspects of the present invention include an irradiation unit that irradiates light to an observation target formed from a plurality of layers, and a light receiving unit that includes a plurality of light receiving units that receive the light backscattered by the observation target. And a selecting unit that identifies and selects a light receiving unit that receives the light by the arbitrary layer among the plurality of light receiving units, and a light propagation path from the irradiation unit to the specified light receiving unit. An optical path length distribution storage unit that stores a model of a propagation optical path length distribution in the plurality of layers, and a time-resolved waveform storage unit that stores a model of a time-resolved waveform of the light received by the specified light receiving unit, A concentration quantification device that quantifies the concentration of a biological component that is a target component in an arbitrary layer of the observation target, a light intensity acquisition unit that acquires the intensity of light received by the specified light receiving unit, and the optical path length An optical path length acquisition unit that acquires optical path lengths of the plurality of layers at a predetermined time of the model of the propagation optical path length distribution, a light intensity acquired by the light intensity acquisition unit, and an optical path length acquisition unit acquired from a storage unit A light absorption coefficient calculating means for calculating a light absorption coefficient of the arbitrary layer based on the optical path lengths of the plurality of layers, and the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means. This is a program for operating as a concentration calculating means for calculating the concentration of the biological component in FIG.
Specifically, an irradiating means for irradiating an observation target formed of a plurality of light scattering medium layers with a short-time pulse light, and a plurality of light receiving the light back-scattered by the observation target by the short-time pulse light A light receiving means having a plurality of light receiving parts, a selection means for selecting a specific light receiving part for receiving the light back-scattered by the arbitrary layer from the plurality of light receiving parts, and the observation target Stores a model of propagation optical path length distribution in each of a plurality of light scattering medium layers arranged on a light propagation path from the irradiating means to the specific light receiving portion of the short-time pulse light to be irradiated Optical path length distribution storage means, and time-resolved waveform storage means for storing a model of a time-resolved waveform of short-time pulsed light that is irradiated to the observation object and received by the specific light receiving unit. A light for acquiring the intensity of the light received by the specific light receiving unit at a predetermined time after the time when the irradiation means irradiates the pulsed light for a short time. Intensity acquisition means, optical path length acquisition means for acquiring the optical path length of each layer of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage means, Light intensity model acquisition means for acquiring the light intensity at the predetermined time of the model of the time-resolved waveform of the short-time pulsed light from the time-resolved waveform storage means, the light intensity acquired by the light intensity acquisition means and the optical path length The light absorption coefficient of the arbitrary layer is calculated based on the optical path length of each of the layers of the plurality of light scattering media acquired by the acquisition unit and the light intensity model acquired by the light intensity model acquisition unit. That the light absorption coefficient calculating means, based on the optical absorption coefficient which the light absorption coefficient calculating means is calculated, a program for operating the concentration calculation means for calculating the concentration of the target component in the arbitrary layer.

It is a schematic block diagram which shows the structure of the blood glucose level measuring apparatus by this invention. It is a graph which shows the propagation optical path length distribution of each layer which the simulation part computed. It is a graph which shows the time-resolved waveform which the simulation part computed. It is a graph which shows the absorption spectrum of the main component of skin. It is sectional drawing of skin tissue. It is sectional drawing of a probe apparatus. It is a 1st flowchart which shows the operation | movement which a blood glucose level measuring apparatus measures a blood glucose level. It is a 2nd flowchart which shows the operation | movement which a blood glucose level measuring apparatus measures a blood glucose level. It is a figure which shows the optical path length of the predetermined time which an optical path length acquisition part acquires.

Hereinafter, a first embodiment of the present invention will be described in detail with reference to the drawings. FIG. 1 is a schematic block diagram showing a configuration of a blood sugar level measuring apparatus according to the first embodiment of the present invention.
The blood glucose level measuring apparatus 100 (concentration determination apparatus) includes a simulation unit 101, an optical path length distribution storage unit 102 (optical path length distribution storage unit), a time-resolved waveform storage unit 103 (time-resolved waveform storage unit), and an irradiation unit 104 (irradiation unit). ), Light receiving unit 105 (light receiving unit), measurement light intensity acquisition unit 106 (light intensity acquisition unit), optical path length acquisition unit 107 (light path length acquisition unit), non-absorption light intensity acquisition unit 108 (light intensity model acquisition unit), A light absorption coefficient calculation unit 109 (light absorption coefficient calculation unit) and a concentration calculation unit 110 (concentration calculation unit) are provided.
The blood glucose level measuring apparatus 100 measures the concentration of glucose (target component) contained in the dermis layer (arbitrary layer) of the skin (observation target).

The simulation part 101 performs the simulation which irradiates light with respect to the skin model whose light absorption coefficient is zero.
The optical path length distribution storage unit 102 stores a propagation optical path length distribution of a skin model having a light absorption coefficient of zero.
The time-resolved waveform storage unit 103 stores a time-resolved waveform of a skin model having a light absorption coefficient of zero.
The irradiation unit 104 irradiates the skin with short-time pulsed light.
The light receiving unit 105 receives light obtained by back-scattering the short-time pulsed light by the skin.
The measurement light intensity acquisition unit 106 acquires the light intensity at a certain time of the light received by the light receiving unit 105.
The optical path length acquisition unit 107 acquires the optical path length at a certain time from the optical path length distribution storage unit 102.
The non-absorption light intensity acquisition unit 108 acquires the light intensity at a certain time from the time-resolved waveform storage unit 103.
The light absorption coefficient calculation unit 109 calculates a light absorption coefficient in the dermis layer of the skin irradiated with the short-time pulse light.
The concentration calculation unit 110 calculates the concentration of glucose contained in the dermis layer.
Here, short-time pulsed light means pulsed light having a pulse width of about 10 psec or less. As the short-time pulse light, pulse light having a pulse width in the range of 0.1 psec to 10 psec may be used.

  In the blood sugar level measuring apparatus 100, the irradiating unit 104 irradiates the skin with short-time pulsed light, and the light receiving unit 105 receives light back-scattered by the short-time pulsed light by the skin, and the measured light intensity acquiring unit 106 Obtains the intensity of light received by the light receiving unit 105 at time t. Next, the optical path length acquisition unit 107 acquires the optical path length of each layer of the skin at time t of the propagation optical path length distribution in the skin model from the optical path length distribution storage unit 102, and the non-absorption light intensity acquisition unit 108 The light intensity at time t of the time-resolved waveform of the short-time pulse light in the skin model is acquired from the waveform storage unit 103.

Next, the light absorption coefficient calculation unit 109 obtains the light intensity acquired by the measurement light intensity acquisition unit 106, the optical path length of each layer of the skin acquired by the optical path length acquisition unit 107, and the light intensity acquired by the non-absorption light intensity acquisition unit 108. Based on the above, the light absorption coefficient of the dermis layer of the skin is calculated, and the concentration calculation unit 110 calculates the concentration of glucose in the dermis layer based on the light absorption coefficient calculated by the light absorption coefficient calculation unit 109.
Thereby, the influence of noise by layers other than the dermis layer can be reduced, and the concentration of glucose contained in the dermis layer can be calculated.

Next, the operation of the blood sugar level measuring apparatus 100 will be described.
The blood glucose level measuring apparatus 100 needs to calculate the propagation optical path length distribution and the time-resolved waveform in each layer of the skin model before measuring the blood glucose level.
First, a method for calculating the propagation optical path length distribution and time-resolved waveform of the skin model will be described.
First, the simulation unit 101 generates a skin model. The skin model is generated by determining the light scattering coefficient, light absorption coefficient, and thickness of each layer of the skin. Here, since the scattering coefficient and thickness of each layer of the skin have little difference between individuals, it is preferable to determine by taking a sample in advance. The thickness of the epidermis layer is approximately 0.3 mm, the thickness of the dermis layer is approximately 1.2 mm, and the thickness of the subcutaneous tissue layer is approximately 3.0 mm.
The light absorption coefficient of the skin model used here is zero. This is because the light absorption amount is calculated using the skin model.

When generating the skin model, the simulation unit 101 performs a simulation of irradiating the skin model with light. At this time, it is necessary to determine the distance between the position of the irradiation unit 104 and the position of the light receiving unit 105. The simulation is preferably performed using the Monte Carlo method. The simulation by the Monte Carlo method is performed as follows, for example.
First, the simulation unit 101 performs calculation for irradiating a skin model with a photon (light beam) as a model of light to be irradiated. Photons irradiated to the skin model move in the skin model. At this time, the photon determines the distance L and the direction θ to the next advancing point by the random number R. The simulation unit 101 calculates the distance L to the point where the photon advances next by Expression (3).

Here, ln (A) represents the natural logarithm of A. Further, μ _s indicates a scattering coefficient of the s-th layer (any one of the epidermis layer, the dermis layer, and the subcutaneous tissue layer) of the skin model.
In addition, the simulation unit 101 calculates the direction θ up to the point where the photon advances next by Expression (4).

However, g shows the anisotropic parameter which is the average of the cosine (cos) of a scattering angle, and the anisotropic parameter of skin is about 0.9.
The simulation unit 101 can calculate the movement path of photons from the irradiation unit 104 to the light receiving unit 105 by repeating the calculations of the above formulas (3) and (4) every unit time. The simulation unit 101 calculates a movement distance for a plurality of photons. For example, the simulation unit 101 calculates the movement distance for 10 ⁸ photons.

FIG. 2 is a graph showing the propagation optical path length distribution of each layer calculated by the simulation unit.
The horizontal axis of FIG. 2 shows the elapsed time from photon irradiation, and the vertical axis shows the logarithmic display of the optical path length. The simulation unit 101 classifies each movement path of photons that reach the light receiving unit 105 for each layer through which the movement path passes. The simulation unit 101 calculates the propagation path length distribution of each layer of the skin as shown in FIG. 2 by calculating the average length of the movement path of the photons that arrived per unit time for each classified layer.

FIG. 3 is a graph showing a time-resolved waveform calculated by the simulation unit.
The horizontal axis in FIG. 3 indicates the elapsed time from the photon irradiation, and the vertical axis indicates the number of photons detected by the light receiving unit 105. The simulation unit 101 calculates the number of photons reaching the light receiving unit 105 per unit time, thereby calculating a time-resolved waveform of the skin model as shown in FIG.
Through the processing described above, the simulation unit 101 calculates the propagation optical path length distribution and time-resolved waveform of the skin model for a plurality of wavelengths. At this time, the simulation unit 101 may calculate the propagation optical path length distribution and the time-resolved waveform for a wavelength at which the difference in the absorption spectrum of the skin main components (water, protein, lipid, glucose, etc.) increases.

FIG. 4 is a graph showing the absorption spectrum of the main component of the skin.
The horizontal axis in FIG. 4 indicates the wavelength of light to be irradiated, and the vertical axis indicates the absorption coefficient. Referring to FIG. 4, the absorption coefficient of glucose becomes maximum when the wavelength is 1600 nm, and the absorption coefficient of water becomes maximum when the wavelength is 1450 nm. For this reason, the simulation unit 101 may calculate the propagation optical path length distribution and the time-resolved waveform for wavelengths that increase the difference in the absorption spectrum of the main component of the skin, such as 1400 nm, 1450 nm, 1500 nm, 1600 nm, 1680 nm, 1720 nm, and 1740 nm.

  When the simulation unit 101 calculates the propagation optical path length distribution and time-resolved waveform of the skin model for a plurality of wavelengths, the simulation unit 101 stores the information on the propagation optical path length distribution in the optical path length distribution storage unit 102 and the time-resolved waveform information as the time-resolved waveform. The data is stored in the storage unit 103.

Here, based on FIG. 5, the structure of the skin tissue to be observed will be described.
As shown in FIG. 5, human skin tissue is formed by three layers of epidermis, dermis, and subcutaneous tissue. The epidermis is an outermost thin layer having a thickness of 0.2 to 0.3 mm, and includes a stratum corneum, a granular layer, a spiny layer, a bottom layer and the like. The dermis is a 0.5 to 2 mm thick layer existing between the epidermis and the subcutaneous tissue, and nerves, hair roots, sebaceous glands, sweat glands, hair follicles, blood vessels, and lymph vessels are present in the dermis. The subcutaneous tissue is a 1 to 3 mm thick layer under the dermis and is mostly made of subcutaneous fat.

  Capillaries and the like have developed in the dermis, and mass transfer according to blood glucose occurs rapidly, and the glucose concentration in the dermis is thought to change following the blood glucose concentration (blood glucose level). ing. Therefore, the blood glucose level measuring apparatus 100 irradiates the surface of the skin tissue with light from the irradiation unit 104, detects the light scattered through the skin tissue, diffused, and back-scattered with the light receiving unit 105. The glucose concentration is measured.

  The irradiation unit 104 includes a light source 104b and an irradiation optical fiber 104a that transmits light emitted from the light source 104b toward the skin. The light receiving unit 105 includes a photoelectric conversion element 105b and a light receiving optical fiber 105a that transmits light diffused and diffused through the skin tissue and emitted from the epidermis toward the photoelectric conversion element 105b. The optical fiber for irradiation 104a and the optical fiber for light reception 105a are connected to a probe device (not shown) so that their optical axes (center axis of the core) are parallel to each other with the center interval of the optical fiber core being separated by a predetermined irradiation / reception interval. It is fixed.

  The light path distribution R reaching the light receiving optical fiber 105a has a U-shape. Actually, there are a plurality of U-shaped paths as shown by dotted lines in the figure, and the propagation distance and propagation time of light in each path are different from each other. The reaching depth of such a path distribution in the skin tissue is an interval between the irradiation unit 104 and the light receiving unit 105, specifically, an irradiation / light receiving interval which is a distance between the core centers of the irradiation optical fiber 104a and the light receiving optical fiber 105a. It changes with W. Therefore, by appropriately setting the irradiation / light receiving interval W between the irradiation unit 104 and the light receiving unit 105, it is possible to measure an absorption spectrum of light mainly transmitted through the dermis.

  6A to 6C are cross-sectional views taken along a plane perpendicular to the optical axes of the irradiation optical fiber 104a and the light receiving optical fiber 105a. In FIG. 6A to FIG. 6C, the optical fiber indicated by symbol A is the irradiation optical fiber 104a, and the optical fibers indicated by symbols B1 to B4 are the light receiving optical fiber 105a.

  The probe device 130 of FIG. 6A includes one irradiation optical fiber 104a arranged at the left end and a plurality of light receiving optical fibers 105a arranged at equal intervals on the right side thereof. In the probe device 130, the irradiation optical fiber 104a and the light source 104b (see FIG. 5) correspond to the irradiation means of the present invention, and a plurality of light receiving optical fibers 105a and photoelectric conversion elements 105b (see FIG. 5) arranged around the irradiation means. This corresponds to the light receiving means of the present invention.

  The irradiation optical fiber 104a and the light receiving optical fiber 105a are arranged in a line in a direction perpendicular to the optical axis. In the probe device 130, irradiation processing of short-time pulsed light to the skin tissue is performed by bringing the tip of the irradiation optical fiber 104 a and the tip of the light receiving optical fiber 105 a exposed at the tip of the probe device 130 into contact with the skin surface. In addition, a light receiving process of light in which short-time pulse light is backscattered by skin tissue is performed.

  The plurality of light receiving optical fibers 105a include a first light receiving optical fiber 105a (indicated by reference numeral B1) disposed at a first irradiation light receiving interval with respect to the irradiation optical fiber 104a, and a first irradiation light receiving interval on the right side thereof. The second light receiving optical fiber 105a (indicated by reference numeral B2) disposed at a second irradiation / light receiving interval larger than the second irradiation / light receiving interval is disposed on the right side with a third irradiation / light receiving interval larger than the second irradiation / light receiving interval. A third light receiving optical fiber 105a (indicated by reference symbol B3) and a fourth light receiving optical fiber 105a (indicated by reference symbol B4) disposed on the right side thereof at a fourth irradiation light receiving interval larger than the third irradiation light receiving interval. And are included.

  One or a plurality of light receiving optical fibers 105a are selected and used as the plurality of light receiving optical fibers 105a depending on the depth of the skin tissue. For example, when it is desired to accurately measure the spectrum of light transmitted through the epidermis, the first light receiving optical fiber 105a (indicated by reference numeral B1) having the smallest irradiation / reception interval is selected to accurately measure the spectrum of light transmitted through the dermis. When it is desired to measure well, a second light receiving optical fiber 105a (indicated by reference numeral B2) arranged at the second irradiation / light receiving interval and a third light receiving optical fiber 105a (reference numeral) arranged at the third irradiation / receiving interval. And a method of selecting (indicated by B3) is used. Further, the thickness of the skin tissue varies from person to person. For example, the thickness of the skin tissue may differ between adults and children, men and women. Therefore, even when information on the dermis is obtained, the optical fiber for receiving light 105a having a larger irradiation / reception interval than that of the subject expected to have a small thickness is used for a subject whose epidermis and dermis are expected to be thick. It is also possible to use.

  Although only four light receiving optical fibers 105a are shown in FIG. 6A, the number of the light receiving optical fibers 105a is not limited to this, and may be three or five or more. If the number of optical fibers 105a for light reception is increased, the depth to reach the skin tissue can be controlled in multiple stages.

  The probe device 131 in FIG. 6B includes one irradiation optical fiber 104a disposed in the center and a plurality of light receiving optical fibers 105a disposed at equal intervals on both sides thereof. In the probe device 131, the irradiation optical fiber 104a and the light source 104b (see FIG. 5) correspond to the irradiation means of the present invention, and a plurality of light receiving optical fibers 105a and photoelectric conversion elements 105b (see FIG. 5) arranged around the irradiation means. This corresponds to the light receiving means of the present invention.

  The irradiation optical fiber 104a and the light receiving optical fiber 105a are arranged in a line in a direction perpendicular to the optical axis. In the probe device 131, the tip of the irradiation optical fiber 104a exposed at the tip of the probe device 131 and the tip of the light receiving optical fiber 105a are brought into contact with the skin surface, thereby irradiating the skin tissue with short-time pulsed light. In addition, a light receiving process of light in which short-time pulse light is backscattered by skin tissue is performed.

  The plurality of light receiving optical fibers 105a include two first light receiving optical fibers 105a (indicated by reference numeral B1) disposed at both sides of the irradiation optical fiber 104a at a first irradiation light receiving interval, and first irradiation on both sides thereof. And two second light receiving optical fibers 105a (indicated by reference numeral B2) disposed at a second irradiation light receiving interval larger than the light receiving interval.

  One or a plurality of light receiving optical fibers 105a are selected and used as the plurality of light receiving optical fibers 105a depending on the depth of the skin tissue. For example, when it is desired to accurately measure the spectrum of light transmitted through the epidermis, the first light receiving optical fiber 105a (indicated by reference numeral B1) having the smallest irradiation / reception interval is selected to accurately measure the spectrum of light transmitted through the dermis. When it is desired to measure well, a first light receiving optical fiber 105a (indicated by reference numeral B1) arranged at the first irradiation / light receiving interval and a second light receiving optical fiber 105a (reference numeral) arranged at the second irradiation / receiving interval. And a method of selecting (indicated by B2) is used. The probe device 131 in FIG. 6B has fewer selectable irradiation and light receiving intervals than the probe device 130 in FIG. 6A, but a plurality of light receiving optical fibers 105a are provided for one irradiation and light receiving interval. As a result, the received light intensity increases. Therefore, measurement with less noise is possible.

  In FIG. 6B, two types of light receiving optical fibers 105a having different irradiation / light receiving intervals are shown, but the number of irradiation / receiving intervals is not limited to two, and may be three or more types. For example, in the case of performing measurement at three types of irradiation / light-receiving intervals, two third light-receiving intervals arranged on both sides of the second light-receiving optical fiber 105a with a third irradiation / light-receiving interval larger than the second irradiation / light-receiving interval. A light receiving optical fiber 105a may be provided. The same applies when there are four or more irradiation / light-receiving intervals.

  The probe device 132 in FIG. 6C includes one irradiation optical fiber 104a disposed at the center and a plurality of light receiving optical fibers 105a disposed around the optical fiber 104a. In the probe device 132, the irradiation optical fiber 104a and the light source 104b (see FIG. 5) correspond to the irradiation means of the present invention, and a plurality of light receiving optical fibers 105a and photoelectric conversion elements 105b (see FIG. 5) arranged around the irradiation means. This corresponds to the light receiving means of the present invention.

  The irradiation optical fiber 104a and the light receiving optical fiber 105a are arranged so as to be packed most closely in a plane perpendicular to the optical axis. That is, the light receiving optical fibers 105a are arranged side by side in the radial direction so as to have an inner angle of 60 ° around the irradiation optical fiber 104a. In the probe device 132, a short-time pulse irradiation process is performed on the skin tissue by bringing the tip of the irradiation optical fiber 104a exposed at the tip of the probe device 132 and the tip of the light receiving optical fiber 105a into contact with the skin surface. In addition, light receiving processing is performed for light in which short-time pulse light is backscattered by skin tissue.

  The plurality of light receiving optical fibers 105a include six first light receiving optical fibers 105a (indicated by reference numeral B1) disposed around the irradiation optical fiber 104a at the first irradiation light receiving interval, and the first irradiation around the first light receiving optical fibers 105a. Six second light receiving optical fibers 105a (indicated by reference numeral B2) arranged at a second irradiation light receiving interval larger than the light receiving interval, and a third irradiation light receiving interval larger than the second irradiation light receiving interval. And six third optical fibers 105a for light reception (indicated by reference numeral B3).

  One or a plurality of light receiving optical fibers 105a are selected and used as the plurality of light receiving optical fibers 105a depending on the depth of the skin tissue. The probe device 132 of FIG. 6C has a larger number of light receiving optical fibers 105a provided for one irradiation / light receiving interval than the probe device 131 of FIG. It becomes possible.

  In FIG. 6B and FIG. 6C, a plurality of light receiving optical fibers 105a are provided for one irradiation light receiving interval. In this case, the light transmitted by the plurality of light receiving optical fibers 105a may be converted into an electrical signal by a photoelectric conversion element provided for each light receiving optical fiber, or a plurality of light receiving light arranged at the same irradiation light receiving interval. The light transmitted by the optical fiber 105a may be condensed on the same light receiving surface of the same photoelectric conversion element by the condensing element, and these may be collectively converted into an electric signal. If the latter method is used, the photoelectric conversion element can be made common to the plurality of light receiving optical fibers 105a, so that the member cost can be reduced.

  When one photoelectric conversion element is provided for each light receiving optical fiber, one light receiving unit is configured by one light receiving optical fiber and one photoelectric conversion element. When one photoelectric conversion element is provided for a plurality of light receiving optical fibers, one light receiving unit is configured by the plurality of light receiving optical fibers and one photoelectric conversion element.

  The irradiation optical fiber 104a and the light receiving optical fiber 105a are desirably dispersion-compensated single-mode optical fibers that compensate for the chromatic dispersion of light having a plurality of wavelengths 1 to q irradiated by the irradiation unit 104. Thereby, measurement errors due to chromatic dispersion can be reduced.

  The irradiation optical fiber 104a and the light receiving optical fiber 105a may be non-dispersion-compensated multimode optical fibers. By using a multimode optical fiber, the light receiving area (core diameter) can be increased compared to the case of using a single mode optical fiber, and measurement with less noise can be performed. However, since a measurement error due to wavelength dispersion becomes large, in the irradiation optical fiber 104a and the light receiving optical fiber 105a, the group delay time difference due to the wavelength dispersion of the plurality of wavelengths 1 to q irradiated by the irradiation unit 104 is different from the skin tissue. The length of each optical fiber may be set to be shorter than the propagation time corresponding to the peak of the propagation optical path length distribution of the epidermis, which is the outermost surface layer among the plurality of light scattering medium layers included in desirable.

  For example, consider the case of using a step index type multimode optical fiber. The group delay time difference of the step index type multimode optical fiber can be expressed by the following equation (5).

  Where To represents the fastest group delay time of light traveling on the optical axis of the optical fiber, Δ represents the relative refractive index difference (= 1%) between the core and the clad of the optical fiber, θc is the critical angle, and n1 is The refractive index of the core is indicated, L indicates the length of the optical fiber, and c indicates the speed of light. To is a path having the shortest propagation distance among a plurality of paths passing through the dermis shown in FIG. 5, that is, a light path in which the arrival depth of short-time pulsed light is near the interface between the epidermis and the dermis. By making the multimode fiber such that ΔTm is shorter than the shortest arrival time of the dermal propagation light, the light intensity of the signal light can be increased as compared with the single mode fiber.

For example, the length of the light receiving optical fiber 105a for receiving the intensity of light within a group delay time difference of 1.0 ps or less is expressed by assuming that the refractive index of the core is 1.5 and the speed of light is 3 × 10 ⁸ m / s. From (5), it is calculated as 20 mm.

  Describing the propagation of light in a multimode fiber geometrically, light traveling at an angle θ1 with respect to the optical axis is d = h while light traveling along the optical axis (θ1 = 0) travels by h. Advance by / (cos θ1). From Snell's law, cos θ1 = n2 / n1 (where n2 represents the refractive index of the cladding and n1 represents the refractive index of the core), so d = h (n1 / n2).

Here, since the relative refractive index difference Δ (= 1−n2 / n1) is 1%, n1 / n2 = 1.01. Therefore, d = 1.01 × h. Since h = 20 mm, d = 20.2 mm. That is, when h is 20 mm, the propagation path difference between h and d is dh = 0.2 mm. Then, since the speed of light traveling in the material having the refractive index n = the speed of light in the air / n, in this case, v = 3 × 10 ⁸ /1.5=2×10 ⁸ m / s. Therefore, propagation path difference = propagation time difference t × light speed = 20 mm from the relationship of propagation time difference t = propagation path difference / light speed.

Next, the operation in which the blood sugar level measuring apparatus 100 measures the blood sugar level will be described.
FIG. 7 is a first flowchart showing an operation in which the blood sugar level measuring apparatus measures the blood sugar level.
First, when the user places the blood glucose level measuring device 100 on the skin and operates the blood glucose level measuring device 100 by pressing a measurement start switch (not shown) or the like, the irradiation unit 104 shortens the wavelength λ ₁ with respect to the skin. Time pulse light is irradiated (step S1). Here, the wavelength λ ₁ is _one of a plurality of wavelengths calculated by the simulation unit 101 for the propagation optical path length distribution and the time-resolved waveform.

  When the irradiation unit 104 irradiates the pulsed light for a short time, the light receiving unit 105 receives the light irradiated from the irradiation unit 104 and back-scattered by the skin (step S2). At this time, the light receiving unit 105 registers the received light intensity for each unit time (for example, every 1 picosecond) from the start of irradiation in the internal memory.

  Here, the target light receiving unit 105 is a specific light receiving unit selected from a plurality of light receiving units provided in the light receiving unit. The plurality of light receiving sections 105 provided in the light receiving means each store an electrical signal corresponding to the amount of received light in a not-shown internal memory as the received light intensity. However, not all the light reception intensity data is acquired by the light absorption coefficient calculation unit 109, and the light reception intensity data stored in the internal memory of the specific light reception unit 105 is selectively selected by the light absorption coefficient calculation unit 109. To be acquired. That is, the light absorption coefficient calculation unit 109 corresponds to the selection unit of the present invention. The light absorption coefficient calculation unit 109 may select a light receiving unit selected directly or indirectly by a user according to a menu screen, or may select a light receiving unit set as a default in advance. As an example of the former, the user directly selects the display buttons such as “light receiving unit 1” and “light receiving unit 2”, or the user selects the age, sex, etc. of the subject on the menu screen. And a device that indirectly selects a light receiving unit associated with sex or the like.

When the light receiving unit 105 completes the light reception, the measurement light intensity acquisition unit 106 stores the received light intensity I (t at different times t stored in the internal memory of the specific light receiving unit 105 selected by the light absorption coefficient calculation unit 109. ) Is acquired in the same number as the number of skin layers (step S3). That is, the measurement light intensity acquisition unit 106 acquires the received light intensities I (t ₁ ) to I (t ₃ ) at _three different times t _{1 to} t ₃ . Here, the reason why the received light intensity is obtained in the same number as the number of skin layers is to calculate the absorption coefficient of each skin layer by simultaneous equations in the processing described later.

Also, the times t ₁ to t _{3 at} which the measurement light intensity acquisition unit acquires the light intensity may be times when the propagation optical path length distribution of each layer of the skin becomes a peak. In other words, the light intensity at the time obtained by adding the time when the optical path length of each layer of the skin is maximized in the graph shown in FIG.

When the measurement light intensity acquisition unit 106 acquires the received light intensities I (t ₁ ) to I (t ₃ ), the optical path length acquisition unit 107 calculates from the propagation optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 102. , the optical path length of each layer of the skin at time _{t 1 ~t 3 L 1 (t} 1) ~L 1 (t 3), L 2 (t 1) ~L 2 (t 3), L 3 (t 1) ~L ₃ (t ₃ ) is acquired (step S4).
Further, when the measurement light intensity acquisition unit 106 acquires the received light intensities I (t ₁ ) to I (t ₃ ), the non-absorption light intensity acquisition unit 108 stores the time of the wavelength λ ₁ stored in the time-resolved waveform storage unit 103. from degradation waveform, the time _t 1 when no absorption in ~t ₃ light intensity _{N (t 1) ~N (t} 3) to get (step S5).

When the optical path length obtaining unit 107 obtains the optical path length of each layer of the skin, non-absorbing at the light intensity acquisition unit ¹⁰⁸ acquires the non-absorbing at the light intensity, the light absorption coefficient calculation unit 109, based on the formula (6), the skin The light absorption coefficients μ _{1 to} μ ₃ of the respective layers are calculated (step S6). Here, the light absorption coefficient μ ₁ indicates the light absorption coefficient of the epidermis layer, the light absorption coefficient μ ₂ indicates the light absorption coefficient of the dermis layer, and the light absorption coefficient μ ₃ indicates the light absorption coefficient of the subcutaneous tissue layer. Show.

Here, ln (A) represents the natural logarithm of A. I _in indicates the light intensity of the short-time pulsed light irradiated by the irradiation unit 104. N _in indicates the number of photons for which the simulation unit 101 has simulated irradiation.
When the light absorption coefficient calculation unit 109 calculates the light absorption coefficients μ _{1 to} μ ₃ of each layer of the skin, the light absorption coefficient calculation unit 109 sets the number of types of wavelengths satisfying xC 2 ≧ α as the number of types of components α to be obtained ( For example, it is determined whether or not the light absorption coefficients μ _{1 to} μ ₃ are calculated for α = 3 → x = 3, α = 4 → x = 4, α = 5 → x = 4) (step S7). . In this embodiment, since the blood sugar level is measured with four main components of skin, water, protein, lipid, and glucose, the light absorption coefficient calculation unit 109 performs light for four wavelengths λ _{1 to} λ ₄ . It is determined whether or not the absorption coefficients μ _{1 to} μ ₃ are calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 101 for the propagation optical path length distribution and the time-resolved waveform.

When the light absorption coefficient calculation unit 109 determines that there are wavelengths λ _{1 to} λ ₄ for which the light absorption coefficients μ _{1 to} μ ₃ are not calculated (step S7: NO), the process returns to step S1 and still has the light absorption coefficient μ. and calculates the light absorption coefficient _μ 1 _{~μ 3} wavelengths lambda ₁ to [lambda] _4, which is not calculated _{1 ~μ 3.}
On the other hand, when the light absorption coefficient calculation unit 109 determines that the light absorption coefficients μ _{1 to} μ ₃ of the wavelengths λ _{1 to} λ ₄ are calculated (step S7: YES), the concentration calculation unit 110 calculates the equation (7 ) To calculate the concentration of glucose contained in the dermis (step S8).

_{However, μ 2 (1) ~μ 2} (4) shows the optical absorption coefficient of the wavelength lambda ₁ to [lambda] ₄ in the dermis layer. Further, g ₁ to g ₄ shows the water respectively in the dermal layer is the main component of skin, proteins, lipids, the molar concentration of glucose. _{Further, ε 1 (1) ~ε 1} (4) shows a molar extinction coefficient of water with respect to the wavelength _{λ 1 ~λ 4, ε 2 (} 1) ~ε 2 (4) is for the wavelength lambda ₁ to [lambda] ₄ Indicates the molar extinction coefficient of the protein, ε _{3 (1) to} ε _{3 ( 4)} indicate the molar extinction coefficient of the lipid for wavelengths λ _{1 to} λ ₄ , and ε _{4 (1) to} ε _{4 (4)} indicate the wavelength The molar extinction coefficient of glucose with respect to λ _{1 to} λ ₄ is shown.
That is, by calculating g ₄ in equation (7), the molar concentration of glucose contained in the dermis can be obtained.

Here, the reason why the molar concentration of glucose can be obtained by the equation (7) will be described. Since the wavelength dependency of the scattering coefficient of the skin is small, the change of the non-absorption light intensity N (t) and the optical path length L _n (t) with respect to the wavelength can be ignored. Further, it can be expressed as Absorbance = Molar extinction coefficient × Molar concentration according to the Beer-Lambert law. Thus, by eliminating the non-absorption light intensity N (t) from the time-resolved measurement obtained at two wavelengths, the relationship between the absorption count difference obtained in the dermis layer and the molar extinction coefficient of each component forming the skin Equation (7) representing the equation can be derived.

  Thus, according to the present embodiment, the concentration of glucose is quantified based on the intensity of light received at a predetermined time by irradiating pulsed light for a short time. Thereby, the absorption count of the dermis layer can be selectively calculated from the light received at a predetermined time. Thereby, the glucose concentration of a specific skin layer can be calculated, the influence of noise by other layers can be reduced, and a highly accurate blood sugar level can be calculated.

  In addition, in Formula (7), the molar concentration of glucose was calculated | required based on the difference of the light absorption coefficient in multiple wavelengths. However, the molar concentration of glucose can be directly determined based on the following equations (8) and (9) regardless of the difference in the light absorption coefficient at a plurality of wavelengths.

Expression (8) is an expression showing the light absorption coefficients μ _{1 to} μ ₃ in each layer.

In Formula (8), μ _{1 (i)} (i = 1 to 4) represents a light absorption coefficient of the wavelength λ _i (i = 1 to 4) in the skin layer, and μ _{2 (i)} (i = 1 to 4). 4) indicates the light absorption coefficient of the wavelength λ _i (i = 1 to 4) in the dermis layer, and μ _{3 (i)} (i = 1 to 4) indicates the wavelength λ _i (i = 1 to 1) in the subcutaneous tissue layer. The light absorption coefficient of 4) is shown. ε _{1 (i)} represents the molar extinction coefficient of water with respect to the wavelength λ _i (i = 1 to 4), and ε _{2 (i)} represents the molar extinction coefficient of the protein with respect to the wavelength λ _i (i = 1 to 4). Ε _{3 (i)} indicates the molar extinction coefficient of lipid for wavelength λ _i (i = 1-4), and ε _{4 (i)} indicates the molar extinction of glucose for wavelength λ _i (i = 1-4). Indicates the coefficient. g _1j , g _2j , g _3j , and g _4j (j = 1 to 3) indicate the molar concentrations of water, protein, lipid, and glucose, which are the main components of the skin in the j layer, respectively. However, j = 1 represents the epidermis layer, j = 2 represents the dermis layer, and j = 3 represents the subcutaneous tissue layer.

Equation (9) is an equation for obtaining water in the dermal layer (j = 2), protein, lipid, the molar concentration of glucose _{g 12, g 22, g 32} , g 42. By calculating the g ₄₂ of formula (9) it is possible to find the molar concentration of glucose contained in the true cortex.

Next, a second embodiment of the present invention will be described in detail.
The second embodiment has the same configuration as the blood glucose level measuring apparatus 100 according to the first embodiment, and includes a measurement light intensity acquisition unit 106, an optical path length acquisition unit 107, a non-absorption light intensity acquisition unit 108, and a light absorption coefficient calculation unit. 109 operations are different.

FIG. 8 is a second flowchart showing the operation of the blood sugar level measuring apparatus for measuring the blood sugar level.
First, when the blood sugar level measuring apparatus 100 is operated, the irradiating unit 104 irradiates the skin with short-time pulsed light having a wavelength λ ₁ (step S11). Here, the wavelength λ ₁ is _one of a plurality of wavelengths calculated by the simulation unit 101 for the propagation optical path length distribution and the time-resolved waveform.

When the irradiation unit 104 emits the short-time pulse light, the light receiving unit 105 receives the light emitted from the irradiation unit 104 and backscattered by the skin (step S12). At this time, the light receiving unit 105 registers the received light intensity for each unit time (for example, every 1 picosecond) from the start of irradiation in the internal memory.
When the light receiving unit 105 completes the light reception, the measurement light intensity acquisition unit 106 acquires the time distribution of the light reception intensity from a certain time to the time τ from the light reception intensity stored in the internal memory of the light reception unit 105 ( Step S13). For example, the time shown in FIG. 9 is selected as the change in light intensity up to time τ. That is, when it is desired to accurately measure the spectrum of light transmitted through the epidermis, the period τ1 of 1 ps to 10 ps is selected. When it is desired to accurately measure the spectrum of light transmitted through the dermis, the period τ2 of 2 ps to 30 ps. Is selected, and a period τ3 of 50 ps to 70 ps is selected when it is desired to accurately detect the spectrum of light transmitted through the subcutaneous tissue. τ1, τ2, and τ3 do not overlap with each other on the time axis, and the measurement start time and the measurement end time are earlier on the time axis as the spectrum of light transmitted through the layer close to the surface of the skin tissue is detected. Set to

When the measurement light intensity acquisition unit 106 acquires the time distribution of the received light intensity until time τ, the optical path length acquisition unit 107 is based on the propagation optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 102. Optical path lengths L _{1 to} L ₃ of each layer of the skin from time to time τ are acquired (step S14).
Further, when the measurement light intensity acquisition unit 106 acquires the received light intensity until time τ, the non-absorption light intensity acquisition unit 108 is from the time-resolved waveform of the wavelength λ ₁ stored in the time-resolved waveform storage unit 103. The non-absorbing light intensity between time and time τ is acquired (step S15).

When the optical path length acquisition unit 107 acquires the optical path length of each layer of the skin, and the non-absorption light intensity acquisition unit 108 acquires the non-absorption light intensity, the light absorption coefficient calculation unit 109 calculates the skin absorption based on the equation (10). The light absorption coefficients μ _{1 to} μ ₃ of each layer are calculated (step S16). Here, the light absorption coefficient μ ₁ indicates the light absorption coefficient of the epidermis layer, the light absorption coefficient μ ₂ indicates the light absorption coefficient of the dermis layer, and the light absorption coefficient μ ₃ indicates the light absorption coefficient of the subcutaneous tissue layer. Show.

Here, ln (A) represents the natural logarithm of A. Further, I (t) indicates the light reception intensity of the light receiving unit 105 at time t, and I _in indicates the light intensity of the short-time pulsed light irradiated by the irradiation unit 104. N (t) represents the non-absorbing light intensity at time t of the time-resolved waveform, and N _in represents the number of photons on which the simulation unit 101 has simulated the irradiation. L ₁ (t) to L ₃ (t) indicate the optical path length of each layer of the skin at time t.

When the light absorption coefficient calculation unit 109 calculates the light absorption coefficients μ _{1 to} μ ₃ of each layer of the skin, the light absorption coefficient calculation unit 109 calculates the light absorption coefficient with respect to the same number of wavelengths as the number of main components of the skin. It is determined whether or not μ _{1 to} μ ₃ are calculated (step S17). In this embodiment, since the blood sugar level is measured with four main components of skin, water, protein, lipid, and glucose, the light absorption coefficient calculation unit 109 performs light for four wavelengths λ _{1 to} λ ₄ . It is determined whether or not the absorption coefficients μ _{1 to} μ ₃ are calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 101 for the propagation optical path length distribution and the time-resolved waveform.

When the light absorption coefficient calculation unit 109 determines that there are wavelengths λ _{1 to} λ ₄ for which the light absorption coefficients μ _{1 to} μ ₃ are not calculated (step S17: NO), the process returns to step S1 and still has the light absorption coefficient μ. and calculates the light absorption coefficient _μ 1 _{~μ 3} wavelengths lambda ₁ to [lambda] _4, which is not calculated _{1 ~μ 3.}
On the other hand, when the light absorption coefficient calculation unit 109 determines that the light absorption coefficients μ _{1 to} μ ₃ of the wavelengths λ _{1 to} λ ₄ are calculated (step S17: YES), the concentration calculation unit 110 uses the above-described formula. Based on (7), the concentration of glucose contained in the dermis is calculated (step S18).

As described above, according to the present embodiment, the absorption coefficients μ _{1 to} μ ₃ are calculated by the integrated value of the optical path length until the time τ. Thus, it is possible to reduce the influence on the calculation result of the absorption coefficient μ ₁ ~μ ₃ by the error contained in the measured received light intensity I (t).

As described above, the embodiment of the present invention has been described in detail with reference to the drawings. However, the specific configuration is not limited to the above, and various design changes and the like can be made without departing from the scope of the present invention. It is possible to
For example, in the embodiment, the case where the concentration quantification method is implemented in the blood glucose level measuring apparatus 100 and the concentration of glucose contained in the dermis layer of the skin is measured has been described. You may use for the other apparatus which quantifies the density | concentration of the target component in the arbitrary layers of the observation object formed from the layer of a light-scattering medium.

  The blood sugar level measuring apparatus 100 described above has a computer system inside. The operation of each processing unit described above is stored in a computer-readable recording medium in the form of a program, and the above processing is performed by the computer reading and executing this program. Here, the computer-readable recording medium means a magnetic disk, a magneto-optical disk, a CD-ROM, a DVD-ROM, a semiconductor memory, or the like. Alternatively, the computer program may be distributed to the computer via a communication line, and the computer that has received the distribution may execute the program.

The program may be for realizing a part of the functions described above.
Furthermore, what can implement | achieve the function mentioned above in combination with the program already recorded on the computer system, and what is called a difference file (difference program) may be sufficient.

DESCRIPTION OF SYMBOLS 100 ... Blood glucose level measuring apparatus, 101 ... Simulation part, 102 ... Optical path length distribution storage part, 103 ... Time-resolved waveform storage part, 104 ... Irradiation part (irradiation means), 104a ... Optical fiber for irradiation, 105 ... Light receiving part, 105a ... Optical fiber for light reception, 106 ... Measurement light intensity acquisition unit, 107 ... Optical path length acquisition unit, 108 ... Non-absorption light intensity acquisition unit, 109 ... Light absorption coefficient calculation unit (selection means), 110 ... Concentration calculation unit

Claims (11)

A concentration quantification device that quantifies the concentration of a biological component that is a target component in an arbitrary layer among observation targets formed from a plurality of layers ,
Irradiating means for irradiating the observation object with light ;
Light receiving means having a plurality of light receiving portions, wherein the light backscattered is received by said observation target,
Among the plurality of light receiving portions, and selection it means for the light by the previous SL any layer selects identifies the light receiving portion to be received,
Light intensity acquisition means for acquiring the intensity of light received by the specified light receiving unit ;
The optical path length distribution storage means for storing the plurality of models of propagation optical path length distribution in the layer on the propagation path of light reaching the light receiving portion that is the specified from the irradiation unit,
A time-resolved waveform storage means for storing a model of the time-resolved waveform of the light received at the specified light receiving unit,
Optical path length acquisition means for acquiring optical path lengths of the plurality of layers at a predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage means;
Based on the optical path length of said plurality of layers in which the optical path length acquisition means, the light intensity in which the light intensity acquisition unit has acquired is acquired, and the light absorption coefficient calculating means for calculating an optical absorption coefficient of the given layer,
Based on the light absorption coefficient calculated by the light absorption coefficient calculation means, a concentration calculation means for calculating the concentration of the biological component in the arbitrary layer;
A concentration determination apparatus comprising: The light intensity acquisition means acquires the light intensity at a plurality of times t _{1 to} t _{m that} are equal to or greater than the number n of the observation target layers,
The light absorption coefficient calculating means includes
Ln indicating the natural logarithm, I (t) indicating the light intensity received by the light receiving means at time t, N (t) indicating the light intensity at time t of the time-resolved waveform model of the short-time pulsed light, and the propagation Using L _i (t) indicating the optical path length of the i-th layer at time t in the model of the optical path length distribution and μ _i indicating the light absorption coefficient of the i-th layer,

Calculate the light absorption coefficient of any layer from
The concentration determination apparatus according to claim 1, wherein: The irradiation means irradiates light having a plurality of wavelengths 1 to q,
The light absorption coefficient calculating means calculates a light absorption coefficient in the arbitrary layer for each of a plurality of wavelengths irradiated by the irradiation means,
The concentration calculating means includes
Μ _{a (i)} indicating the light absorption coefficient of the wavelength i in the a-th layer which is the arbitrary layer, g _j indicating the molar concentration of the j-th component forming the observation object, and light absorption of the j-th component with respect to the wavelength i Ε _{j (i)} indicating a coefficient, p indicating the number of main components forming the observation object, q indicating the number of types of wavelengths irradiated by the irradiation unit,

Calculate the concentration of the target component in the arbitrary layer from
The concentration determination apparatus according to claim 2, wherein The irradiation position where to irradiate light to the observation target from the illumination means, before Symbol light receiving position where to exit toward the light receiving portion of light backscattered from the observed object by the observation target, the irradiation position And the light receiving position as an irradiation light receiving interval, the light receiving means has a plurality of light receiving portions having different irradiation light receiving intervals, and the selecting means is determined according to the irradiation light receiving interval. 4. The concentration quantification apparatus according to claim 3, wherein a light receiving unit having an irradiation light receiving interval capable of propagating light to the arbitrary layer is selected based on an arrival depth of light into the observation target. The irradiation means includes an irradiation optical fiber that transmits light to the surface of the observation target , and the light receiving unit includes a light reception optical fiber that transmits light backscattered by the observation target; The optical fiber for light reception is attached to a probe device that fixes the center interval between both optical fiber cores apart by a predetermined irradiation light reception interval, and the distal end portion of the irradiation optical fiber exposed at the distal end portion of the probe device; by contacting the front end portion of the light receiving optical fiber to the surface of the observation target, and light irradiation treatment to the observed object, that the previous SL light makes the light receiving processing of the light backscattered by the observed object The concentration determination apparatus according to claim 4, wherein:   6. The concentration quantification apparatus according to claim 5, wherein the light receiving unit includes a plurality of light receiving optical fibers arranged at equal irradiation light receiving intervals.   The density according to claim 6, wherein the light receiving unit includes a condensing element that condenses light transmitted by a plurality of light receiving optical fibers arranged at equal irradiation and light receiving intervals on the same light receiving surface. A quantitative device.   The optical fiber for irradiation and the optical fiber for light reception are dispersion-compensated single mode optical fibers that compensate for chromatic dispersion of the light of the plurality of wavelengths 1 to q irradiated by the irradiation unit. The concentration quantification apparatus according to any one of the above.   The optical fiber for irradiating and the optical fiber for receiving light have a group delay time difference associated with wavelength dispersion of the light of the plurality of wavelengths 1 to q irradiated by the irradiating means, the layer on the most surface side among the plurality of light scattering medium layers The concentration quantification apparatus according to claim 5, wherein the concentration quantification apparatus is shorter than a propagation time corresponding to a peak of the propagation optical path length distribution. Irradiating means for irradiating light to the observation target, which is formed from a plurality of layers, and the light receiving means having a plurality of light receiving portions, wherein the light backscattered is received by said observation target, among the plurality of light receiving portions, before selection means for said light is selected to identify the light-receiving portion which is received by the serial arbitrary layer, from the irradiation unit of the propagation path length distribution in the plurality of layers on the propagation path of light reaching the light receiving portion, which is the specific comprising an optical path length distribution storage means for storing a model, and a time-resolved waveform storage means for storing a model of the time-resolved waveform of the light received at the specified light receiving unit, the purpose of any layer of the observed object A concentration quantification method using a concentration quantification device for quantifying the concentration of a biological component as a component ,
Light intensity acquisition unit includes a light receiving unit that is pre-Symbol identified obtains the intensity of the received light,
The optical path length acquisition means acquires the optical path lengths of the plurality of layers at a predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage means ,
Light absorption coefficient calculating means, based on the optical path length of the plurality of layers in which the light intensity obtaining unit light intensities acquired with the optical path length acquisition means has acquired, and calculates the light absorption coefficient of the given layer,
The concentration calculation means calculates the concentration of the biological component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculation means.
Concentration determination method characterized by this. Irradiating means for irradiating light to the observation target, which is formed from a plurality of layers, and the light receiving means having a plurality of light receiving portions, wherein the light backscattered is received by said observation target, among the plurality of light receiving portions, before selection means for said light is selected to identify the light-receiving portion which is received by the serial arbitrary layer, from the irradiation unit of the propagation path length distribution in the plurality of layers on the propagation path of light reaching the light receiving portion, which is the specific comprising an optical path length distribution storage means for storing a model, and a time-resolved waveform storage means for storing a model of the time-resolved waveform of the light received at the specified light receiving unit, the purpose of any layer of the observed object A concentration quantification device that quantifies the concentration of the biological component that is a component ,
Light intensity acquisition means for acquiring the intensity of light received by the specified light receiving unit;
Wherein the optical path length distribution storage means, wherein in the constant time at the propagation model of the optical path length distribution, the optical path length acquisition means for acquiring an optical path length of the plurality of layers,
Based on the optical path length of said plurality of layers in which the light intensity obtaining unit light intensities acquired with the optical path length acquisition means has acquired, the light absorption coefficient calculating means for calculating an optical absorption coefficient of the given layer,
Concentration calculating means for calculating the concentration of the biological component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means;
Program to operate as.

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