JP2013138811A - Concentration determination apparatus, concentration determination method, and program - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a concentration determination apparatus, a concentration determination method, and a program which highly accurately calculates the concentration of a target component in any layer of an observed object.SOLUTION: A concentration determination apparatus 100 for determining the concentration of a target component in an arbitrary layer of an observed object constituted of a plurality of layers, includes: an optical path length distribution storage unit 102; a time-resolved waveform storage unit 103; an irradiation unit 104 for irradiating, with short time pulse light, the observed object adjusted so that the absorption state of a surface has a prescribed absorption state; a light receiving unit 105 for receiving light in which the short time pulse light is backscattered by the observed object and which is emitted from the surface of the observed object whose absorption state is adjusted; an absorption coefficient calculation unit 110; and a concentration calculation unit 113.

Description

  Some aspects of the present invention include a concentration quantification apparatus, a concentration quantification method, and a program for non-invasively and accurately quantifying the concentration of a target component in an arbitrary layer among observation targets including a plurality of layers. About.

In recent years, Japan is in the age of satiety, and the number of diabetic patients continues to increase every year. Therefore, the number of patients with diabetic nephritis will continue to increase every year. As a result, the number of patients with chronic renal failure continues to increase by 10,000 each year, and the number of patients exceeds 280,000.
On the other hand, with the arrival of an aging society, the importance of metabolic rate management in individuals is rapidly increasing in response to increasing demand for preventive medicine. In particular, it is known that blood glucose level measurement can be understood by measuring glucose levels before and after meals. By evaluating the response of glucose metabolism at the very early stage of diabetes, early treatment based on early diagnosis of diabetes becomes possible.

Conventionally, the blood sugar level is measured by collecting blood from a vein such as an arm or a fingertip and measuring the enzyme activity for glucose in the blood. However, such a blood glucose level measurement method has various problems such as complicated blood collection, pain associated with blood collection, and risk of infection.
In addition, as a method for continuously measuring blood glucose level, an instrument that continuously measures glucose corresponding to blood glucose level with a needle inserted into a vein has been developed in the United States. is there. However, since the injection needle is left pierced in the vein, there is a risk that the needle may come off during the measurement of the blood glucose level and a risk of infection.
Therefore, development of a blood glucose level measuring apparatus that can measure blood glucose level frequently without blood collection and that is free from the risk of infectious diseases is demanded. Furthermore, there is a demand for the development of a blood glucose level measuring device that can be easily and always worn and can be miniaturized.

As a device for non-invasively measuring blood glucose levels using near-infrared continuous light, a device applying a general spectroscopic measurement principle using the principle of molecular absorption has been proposed (for example, a patent) References 1 and 2).
This apparatus corresponds to the case where the biological component concentration is quantified using the infrared spectrum of the skin, and an error occurs in the quantification of the biological component concentration due to the influence of subcutaneous fat. More specifically, it is an apparatus that irradiates the skin with near-infrared continuous light and calculates the glucose concentration from the amount of light absorption.
In this apparatus, a calibration curve indicating the relationship between the glucose concentration, the wavelength of near-infrared light to be irradiated, and the light absorption amount is prepared in advance. Then, the skin is irradiated with near-infrared continuous light, and the return light from the skin is scanned in a certain wavelength range using a monochromator or the like, and the amount of light absorbed for each wavelength in the wavelength range is determined. The amount of light absorbed at the wavelength is compared with the calibration curve. Thereby, the glucose concentration in the blood, that is, the blood glucose level is calculated.

Further, skin properties are classified from the absorbance at the specific absorption wavelength of subcutaneous fat selected from the wavelength range of 1700 nm to 1800 nm, and a calibration formula is selected as a substitute characteristic of “skin thickness”.
Further, the “skin thickness” estimated as a preliminary distance between the near-infrared light receiving portion and the light emitting portion is 650 μm is determined to be 1.2 mm or more and less than 1.2 mm, and the light receiving portion and the light emitting portion are determined. The calibration formula is selected after selecting the interval between 650 μm and 300 μm.

On the other hand, for biodiagnosis using near-infrared light, for example, the amount of absorption of near-infrared light in the main skin component is measured by biological tissue imaging using a time-resolved measurement method, Methods are known for determining the proportion of each component, for example, the glucose concentration corresponding to blood sugar.
Since the absorption amount of this skin main component is wavelength-dependent, usually, multiple spectra are created in advance by varying the variation factors that affect the quantification of the skin main component in multiple ratios by multivariate analysis. . Then, the spectrum of the measurement result of the absorption amount of near-infrared light in the skin main component is compared with the above-mentioned plurality of spectra, and a matching spectrum is selected from these spectra. Thereby, each ratio of the skin main component is estimated.

Japanese Patent No. 3931638 Japanese Patent No. 3994588

However, a conventional device that measures blood glucose level non-invasively using near-infrared continuous light cannot measure only the amount of light absorbed in a path that passes through a specific depth. Therefore, there is a problem that the glucose concentration corresponding to blood glucose in the skin main component at a specific depth cannot be accurately quantified.
In the device of Patent Document 1, the depth from the skin surface to the subcutaneous fat is defined as “skin thickness”, and the skin properties are classified from the absorbance at the specific absorption wavelength of the subcutaneous fat. To substitute the depth to fat as “skin thickness”, (1) the boundary between the dermis layer and the subcutaneous tissue layer of the skin is not uniform as the depth from the surface of the skin, and (2) the dermis The layer has a sweat gland that secretes fat and stores fat secretions. (3) When classifying skin properties from the absorbance at the specific absorption wavelength of subcutaneous fat, cells and interstitial fluid in the dermis layer Has a problem because it contains fat, and it is difficult to distinguish between the dermal layer and subcutaneous fat.

In general, when the concentration of biological components is quantified using the infrared spectrum of the skin, the depth of the optical path from the skin surface in the skin is roughly estimated by the banana shape characteristic determined by the distance between the light receiving part and the light emitting part. The For example, if the distance between the light receiving part and the light emitting part is 650 μm, the depth of the light path from the skin surface is estimated to be 325 μm, and if the distance between the light receiving part and the light emitting part is 300 μm, the skin surface of the light path Is estimated to be 150 μm.
However, in the apparatus of Patent Document 1, for the above-mentioned reasons, it is not possible to specify a site where the biological component concentration is quantified using the infrared spectrum of the skin. Therefore, it is not possible to selectively measure the absorbance in the optical path that passes through the specific site, with the reticular layer (Stratum reticulare) in which glucose is present as one of the interstitial components in the dermis layer as the specific site.

In patent document 2, the sensing part provided with the near infrared irradiation part and the light-receiving part, the holding means which makes this sensing part contact skin with the contact pressure of 100-750 gf / cm < ² >, this sensing part and skin surface There is disclosed a blood glucose level measuring device comprising a measuring means for measuring the contact pressure of the blood pressure sensor and a notifying means for notifying the fact when the contact pressure becomes an appropriate contact pressure.
However, even in this blood glucose level measuring apparatus, it is impossible to measure the state in which light enters the skin from the irradiation unit and the state in which light scattered back from the skin enters the light receiving unit.

  The present invention has been made in view of the above points, and its purpose is to provide a concentration quantification apparatus, a concentration quantification method, and a program capable of calculating the concentration of a target component in an arbitrary layer to be observed with high accuracy. It is to provide.

  Some aspects of the present invention have been made in order to solve the above-described problems, and are concentration quantification apparatuses for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of a plurality of layers. An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers of the short-time pulse light irradiated to the observation target, and the short irradiation to the observation target. A time-resolved waveform storage unit that stores a model of a time-resolved waveform of time-pulsed light, and an irradiation unit that irradiates the observation target with a short-time pulsed light so that the surface absorption state is in a predetermined absorption state, When the short-time pulse light is back-scattered by the observation target and receives light emitted from the surface of the observation target with the absorption state adjusted, and when the irradiation unit irradiates the short-time pulse light A light intensity acquisition unit that acquires the intensity of light received by the light receiving unit at a predetermined time thereafter, and the optical path length distribution storage unit from the optical path length distribution model at the predetermined time of the plurality of layers. An optical path length acquisition unit that acquires an optical path length of each layer, and a light intensity model acquisition that acquires a light intensity model at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage unit , The light intensity acquired by the light intensity acquisition unit, the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light intensity acquired by the light intensity model acquisition unit An absorption coefficient calculation unit that calculates an absorption coefficient of the arbitrary layer based on the model, and a concentration that calculates the concentration of the target component in the arbitrary layer based on the absorption coefficient calculated by the absorption coefficient calculation unit Calculation unit , Characterized in that it comprises a.

According to this configuration, the absorption coefficient of an arbitrary layer can be selectively calculated from the time-resolved waveform of received light. Therefore, by calculating the concentration of the target component based on the calculated absorption coefficient, it is possible to reduce the influence of noise due to the other layers and perform highly accurate concentration quantification.
Here, in the process (calculation process) in which the absorption coefficient calculation unit calculates the absorption coefficient, it is not assumed that extra absorption other than the target component occurs in the observation target. However, the actual skin surface condition varies depending on the external environment (for example, dryness, wetness, etc.) and individual differences (for example, age, sex, etc.). For this reason, the skin surface state assumed in the calculation process may be different from the skin surface state when actually measuring the concentration of the target component in an arbitrary layer to be observed. If the configuration is such that the light emitted from the irradiator directly enters the skin surface, the concentration of the target component in any layer to be observed can be accurately measured based on changes in the skin surface properties due to the external environment or individual differences. Can not do it. On the other hand, according to the configuration of the present invention, the concentration of the target component in an arbitrary layer of the observation target is measured in a state where the absorption state of the surface of the observation target is adjusted to a predetermined absorption state. For this reason, it is possible to avoid variation in the calculated value of the absorption coefficient in any layer of the skin due to changes in the properties of the skin surface due to the external environment and individual differences during actual measurement. Therefore, the concentration of the target component in an arbitrary layer to be observed can be calculated with high accuracy.

  In some embodiments of the present invention, it is preferable that the absorption state of the surface of the observation target is adjusted by bringing a regulator that adjusts the absorption state into contact with the surface of the observation target.

  As a method of adjusting the absorption state of the surface to be observed, a method of adjusting the external environment to a predetermined atmosphere is also conceivable, but this requires a large-scale facility. On the other hand, according to this configuration, the absorption state of the surface of the observation target can be adjusted by a simple method of bringing the adjusting agent into contact with the surface of the observation target. Therefore, it becomes easy to calculate the concentration of the target component in any layer to be observed with high accuracy.

  In some embodiments of the present invention, the adjusting agent is preferably a liquid or gel-like member.

  According to this configuration, the absorption state of the surface of the observation target can be adjusted by a simple method (for example, a method of applying the adjusting agent to the surface of the observation target). Therefore, it becomes easy to calculate the concentration of the target component in any layer to be observed with high accuracy.

  Further, according to some aspects of the present invention, the irradiation unit may be configured such that the short-time pulsed light is transmitted to the observation target via the adjustment agent in a state where the surface irradiated with the short-time pulse light is in contact with the adjustment agent. And the light receiving unit receives the light backscattered by the observation object via the adjustment agent in a state where the surface receiving light scattered by the observation object is in contact with the adjustment agent. Is preferred.

  According to this configuration, since the adjustment agent is filled between the light irradiation surface of the irradiation unit and the light receiving surface of the light receiving unit and the observation target, there is no influence of interface reflection and the influence of disturbance can be further suppressed. It becomes.

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 (where n is 1 or more). , M is a natural number greater than or equal to n), the absorption coefficient calculation unit is I (t) indicating the light intensity received by the light receiving unit at time t, and the time t of the time-resolved waveform model of the short-time pulsed light N (t) indicating the light intensity at, Li (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 absorption coefficient of the i-th layer, The absorption coefficient of an arbitrary layer is calculated from (1).

According to this configuration, the light intensity acquisition unit acquires the light intensity at a plurality of times t _{1 to} t _m of an arbitrary layer, and the absorption coefficient calculation unit calculates the absorption coefficient of the arbitrary layer by the above formula (1 ).
In this way, by measuring the time-resolved backscattered light, backscattered light from layers other than any layer can be reduced as noise, and the influence of the layer other than any layer on the concentration of the target component can be reduced. Can be reduced. Therefore, the concentration of the target component can be measured with higher accuracy.

  Further, in some aspects of the present invention, the light intensity acquisition unit acquires light intensity from a predetermined time to at least a predetermined time τ, and the absorption coefficient calculation unit has the light receiving unit at time t. I (t) indicating the received light intensity, N (t) indicating the light intensity at time t of the time-resolved waveform model of the short-time pulsed light, and the optical path of the i-th layer at time t of the optical path length distribution model The absorption coefficient of an arbitrary layer is calculated from the following equation (2) using Li (t) indicating the length, n indicating the number of layers to be observed, and μi indicating the absorption coefficient of the i-th layer. Features.

According to this configuration, the light intensity acquisition unit acquires a temporal change in light intensity between a predetermined time and at least a predetermined time τ, and the absorption coefficient calculation unit calculates the absorption coefficient of an arbitrary layer from the above equation. Calculate from (2).
In this way, by measuring the time-resolved backscattered light, backscattered light from layers other than any layer can be reduced as noise, and the influence of the layer other than any layer on the concentration of the target component can be reduced. Can be reduced. Therefore, the concentration of the target component can be measured with higher accuracy.

In some embodiments of the present invention, the irradiation unit irradiates light having a plurality of wavelengths 1 to q, and the absorption coefficient calculation unit includes a plurality of irradiation units irradiated with the absorption coefficient in the arbitrary layer. The concentration calculation unit calculates μa (i) indicating the absorption coefficient of the wavelength i in the a-th layer, which is the arbitrary layer, and gj indicating the molar concentration of the j-th component forming the observation target. Ε _{j (i)} indicating the absorption coefficient for the wavelength i of the j-th component, p indicating the number of main components forming the observation object, and q indicating the number of types of wavelengths irradiated by the irradiation unit, The concentration of the target component in the arbitrary layer is calculated from the equation (3).

According to this configuration, the irradiation unit emits light having a plurality of wavelengths 1 to q, the absorption coefficient calculation unit calculates the absorption coefficient in an arbitrary layer for each of the plurality of wavelengths irradiated by the irradiation unit, and calculates the concentration. The unit calculates the concentration of the target component in an arbitrary layer from the above equation (3).
In this way, by measuring the time-resolved backscattered light, backscattered light from layers other than any layer can be reduced as noise, and the influence of the layer other than any layer on the concentration of the target component can be reduced. Can be reduced. Therefore, the concentration of the target component can be measured with higher accuracy.

  In some embodiments of the present invention, it is preferable that the observation target is skin, and the adjusting agent is a moisturizing agent that moisturizes the skin surface.

  According to this configuration, the surface of the skin can be kept fresh and kept. For this reason, even if the skin surface is dry due to changes in the skin surface properties due to external environment or individual differences, the surface condition of the skin assumed in the calculation process and the target component in any layer actually observed The surface condition of the skin when measuring the concentration can be matched. Therefore, the concentration of the target component in an arbitrary layer to be observed can be calculated with high accuracy.

  In some embodiments of the present invention, the observation target is skin, the arbitrary layer is a dermis layer, and the target component is glucose.

  According to this configuration, by calculating the concentration of glucose contained in the dermis layer based on the calculated absorption coefficient, it is possible to reduce the influence of noise due to other layers and to determine the glucose concentration with high accuracy. it can.

  Further, some aspects of the present invention provide an optical path length for storing a model of an optical path length distribution in each of the plurality of layers of short-time pulse light irradiated to an observation target composed of a plurality of layers. A distribution storage unit; and a time-resolved waveform storage unit that stores a model of a time-resolved waveform of the short-time pulsed light that irradiates the observation target. A concentration quantification method using a concentration quantification device for quantification, wherein the irradiation unit irradiates the observation target adjusted so that the absorption state of the surface becomes a predetermined absorption state for a short time, and the light receiving unit The short-time pulse light is backscattered by the observation target and receives light emitted from the surface of the observation target adjusted in the absorption state, and the light intensity acquisition unit is configured to receive the short-time pulse. Light An intensity of light received by the light receiving unit at a predetermined time after the predetermined time, and an optical path length acquisition unit is configured to obtain the plurality of the optical path length distribution models at the predetermined time from the optical path length distribution storage unit. An optical path length of each of the layers, and a light intensity model acquisition unit acquires a light intensity model at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage unit The absorption coefficient calculation unit includes the light intensity acquired by the light intensity acquisition unit, the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light intensity model acquisition unit. Based on the acquired light intensity model, the absorption coefficient of the arbitrary layer is calculated, and the concentration calculation unit calculates the target component in the arbitrary layer based on the absorption coefficient calculated by the absorption coefficient calculation unit. To calculate the concentration And butterflies.

According to this method, the absorption coefficient of an arbitrary layer can be selectively calculated from the time-resolved waveform of received light. Therefore, by calculating the concentration of the target component based on the calculated absorption coefficient, it is possible to reduce the influence of noise due to the other layers and perform highly accurate concentration quantification.
Here, in the process (calculation process) in which the absorption coefficient calculation unit calculates the absorption coefficient, it is not assumed that extra absorption other than the target component occurs in the observation target. However, the actual skin surface condition varies depending on the external environment (for example, dryness, wetness, etc.) and individual differences (for example, age, sex, etc.). For this reason, the skin surface state assumed in the calculation process may be different from the skin surface state when actually measuring the concentration of the target component in an arbitrary layer to be observed. If the light emitted from the irradiation unit is directly incident on the surface of the skin, the concentration of the target component in any layer to be observed can be accurately measured based on changes in the properties of the skin surface due to the external environment or individual differences. Can not do it. On the other hand, according to the method of the present invention, the state of absorption of the surface of the observation target is adjusted to the absorption state assumed when calculating the optical path length distribution model and the time-resolved waveform model. Measure the concentration of the target component in any layer. For this reason, it is possible to avoid variation in the calculated value of the absorption coefficient in any layer of the skin due to changes in the properties of the skin surface due to the external environment and individual differences during actual measurement. Therefore, the concentration of the target component in an arbitrary layer to be observed can be calculated with high accuracy.

  Further, some aspects of the present invention provide an optical path length for storing a model of an optical path length distribution in each of the plurality of layers of short-time pulse light irradiated to an observation target composed of a plurality of layers. A distribution storage unit; and a time-resolved waveform storage unit that stores a model of a time-resolved waveform of the short-time pulsed light that irradiates the observation target. An irradiation procedure for irradiating the observation target adjusted so that the absorption state of the surface is in a predetermined absorption state to the computer of the concentration determination apparatus for quantification, and the short-time pulse light is rearward depending on the observation target A light receiving procedure for receiving light emitted from the surface of the observation target that has been scattered and the absorption state is adjusted, and a predetermined time after the time when the short-time pulse light is emitted in the irradiation procedure A light intensity acquisition procedure for acquiring the intensity of light received in the light reception procedure, and an optical path of each of the plurality of layers at the predetermined time of the model of the optical path length distribution from the optical path length distribution storage unit An optical path length acquisition procedure for acquiring a length; a light intensity model acquisition procedure for acquiring a light intensity model at the predetermined time of a model of the time-resolved waveform of the short-time pulsed light from the time-resolved waveform storage unit; Based on the light intensity acquired in the procedure, the optical path length of each of the plurality of layers acquired in the optical path length acquisition procedure, and the light intensity model acquired in the light intensity model acquisition procedure, An absorption coefficient calculation procedure for calculating an absorption coefficient of an arbitrary layer, and a concentration calculation procedure for calculating the concentration of the target component in the arbitrary layer based on the absorption coefficient calculated in the absorption coefficient calculation procedure. Characterized in that to.

According to this program, the absorption coefficient of an arbitrary layer can be selectively calculated from the time-resolved waveform of received light. Therefore, by calculating the concentration of the target component based on the calculated absorption coefficient, it is possible to reduce the influence of noise due to the other layers and perform highly accurate concentration quantification.
Here, in the process (calculation process) in which the absorption coefficient calculation unit calculates the absorption coefficient, it is not assumed that extra absorption other than the target component occurs in the observation target. However, the actual skin surface condition varies depending on the external environment (for example, dryness, wetness, etc.) and individual differences (for example, age, sex, etc.). For this reason, the skin surface state assumed in the calculation process may be different from the skin surface state when actually measuring the concentration of the target component in an arbitrary layer to be observed. If the configuration is such that the light emitted from the irradiator directly enters the skin surface, the concentration of the target component in any layer to be observed can be accurately measured based on changes in the skin surface properties due to the external environment or individual differences. Can not do it. On the other hand, according to the configuration of the present invention, the concentration of the target component in an arbitrary layer of the observation target is measured in a state where the absorption state of the surface of the observation target is adjusted to a predetermined absorption state. For this reason, it is possible to avoid variation in the calculated value of the absorption coefficient in any layer of the skin due to changes in the properties of the skin surface due to the external environment and individual differences during actual measurement. Therefore, the concentration of the target component in an arbitrary layer to be observed can be calculated with high accuracy.

It is a schematic block diagram which shows the structure of the blood glucose level measuring apparatus which concerns on 1st Embodiment of this invention. It is a schematic diagram which shows the cross section of a human skin tissue. It is a graph which shows the spectral absorption coefficient in skin tissue. It is a schematic diagram which shows the arrangement | positioning state of a regulator. It is a schematic diagram which shows the modification of the arrangement | positioning state of a regulator. It is a figure which shows the relationship between the wavelength of light, and the penetration depth to skin. It is a graph which shows 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 a flowchart which shows the operation | movement which the blood glucose level measuring apparatus which concerns on 1st Embodiment of this invention measures a blood glucose level. 3 is a flowchart showing an operation of the blood sugar level measuring apparatus for measuring a blood sugar level. It is a figure which shows the relationship between the absorption coefficient in a dermis layer, and an integration area. It is a figure which shows the relationship between the estimation error rate of the absorption coefficient in a dermis layer, and an integration area. It is a flowchart which shows the operation | movement which the blood glucose level measuring apparatus which concerns on 2nd Embodiment of this invention measures a blood glucose level. 3 is a flowchart showing an operation of the blood sugar level measuring apparatus for measuring a blood sugar level.

Hereinafter, with reference to the drawings, a concentration quantification apparatus, a concentration quantification method and a program for carrying out a program of the present invention will be described.
In the present invention, a blood glucose level measuring device will be described as an example of a concentration determination device, the skin of a human palm as an observation target, and glucose as a target component.

(First embodiment)
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, a time-resolved waveform storage unit 103, an irradiation unit 104, a light receiving unit 105, a measured light intensity acquisition unit 106, and an optical path length acquisition unit 107. A non-absorption light intensity acquisition unit 108 (light intensity model acquisition unit), an integration interval calculation unit 109, an absorption coefficient calculation unit 110, an absorption coefficient distribution storage unit 111, an absorption coefficient acquisition unit 112, and a concentration calculation unit 113.

  The blood glucose level measuring device 100 is a device that non-invasively quantifies the concentration of glucose (target component) contained in a dermis layer (arbitrary layer) of a plurality of layers constituting skin (observation target) such as a palm. .

  The simulation part 101 performs the simulation which irradiates light with respect to the skin model whose absorption coefficient is zero. The simulation unit 101 calculates a model of an optical path length distribution in each layer constituting the skin of short-time pulse light irradiated to the skin. In addition, the simulation unit 101 calculates a model of a time-resolved waveform of short-time pulsed light that is applied to the skin.

  The optical path length distribution storage unit 102 stores a model of the optical path length distribution in each layer constituting the skin of the short-time pulse light applied to the skin calculated by the simulation unit 101. Here, the optical path length distribution of the skin model having zero absorption coefficient is stored.

Here, the short-time pulsed light is pulsed light whose pulse width is shorter than the time required for light to propagate directly from the irradiation unit 104 to the light receiving unit 105 in the air. 0.1 ps to 10 ps refers to pulsed light having a time interval of 1 ps to 100 ps between two pulsed lights.
The optical path length distribution is a distribution function representing the length (optical path length) of the movement path of light (photons) based on the time until the light (photons) reaches the light receiving unit 105.

  The time-resolved waveform storage unit 103 stores a model of a time-resolved waveform of short-time pulsed light that is applied to the skin calculated by the simulation unit 101. Here, the time-resolved waveform of the skin model having zero absorption coefficient is stored.

  Here, the time-resolved waveform of the short-time pulse light represents the intensity of the light (photon) received by the light receiving unit 105 as a distribution function based on the elapsed time from the irradiation of the short-time pulse light. It is.

  If the simulation result in the simulation unit 101 is stored in the optical path length distribution storage unit 102 and the time-resolved waveform storage unit 103, it is not necessary to provide the simulation unit 101 separately.

  The irradiation unit 104 irradiates the skin with short-time pulsed light. The plurality of short-time pulse lights emitted by the irradiating unit 104 is light having a wavelength that increases the orthogonality of the absorption spectrum distribution of each component of the main components constituting the skin, that is, each of the main components constituting the skin. Among the components, the maximum value of the absorption spectrum of a specific component in a certain main component includes light having a wavelength that is significantly different from the maximum value of the absorption spectrum of another component.

  The light receiving unit 105 receives light obtained by back-scattering the short-time pulsed light by the skin. The light receiving unit 105 includes an internal memory (not shown) for recording the received light intensity. The internal memory may be replaced with an external memory that is electrically connected to the light receiving unit 105.

Here, the structure of the human skin tissue to be observed will be described.
FIG. 2 is a schematic diagram showing a cross section of a human skin tissue. The skin 31 is composed of three layers, an epidermis layer 32, a dermis layer (arbitrary layer) 33, and a subcutaneous tissue layer 34.

  The epidermis layer 32 is an outermost thin layer having a thickness of 0.2 mm to 0.3 mm, and is a layer containing about 60% of water, protein, lipid and glucose, and includes a stratum corneum, a granular layer, and a spiny layer. , Including bottom layer.

  The dermis layer 33 is a layer formed under the epidermis layer 32 and having a thickness of 0.5 mm to 2 mm, and is a layer containing approximately 60% of water, protein, lipid and glucose. In the dermis layer 33, there are nerves, hair roots, sebaceous glands, sweat glands, hair follicles, blood vessels, lymph vessels, and the like.

  The subcutaneous tissue layer 34 is a layer having a thickness of 1 to 3 mm formed under the dermis layer 33. The subcutaneous tissue layer 34 is mostly made of subcutaneous fat containing approximately 90% or more of lipids and the balance being water.

  Capillaries and the like are developed in the dermis layer 33, mass transfer according to blood glucose occurs rapidly, and the glucose concentration in the dermis layer 33 follows the blood glucose concentration (blood glucose level). It is thought to change.

  By the way, in the process (calculation process) of calculating the absorption coefficient by the absorption coefficient calculation unit, it is not assumed that extra absorption other than the target component occurs in the observation target. However, the actual skin surface condition varies depending on the external environment (for example, dryness, wetness, etc.) and individual differences (for example, age, sex, etc.). Therefore, the skin surface state assumed in the calculation process may be different from the skin surface state when actually measuring the concentration of the target component in any layer of the skin. If the configuration is such that the light emitted from the irradiator directly enters the surface of the skin, the concentration of the target component in any layer of the skin can be accurately measured by changes in the properties of the skin surface due to the external environment or individual differences. I can't.

  Therefore, in the present embodiment, the irradiation unit 104 that irradiates the skin for a short time with the pulse adjusted so that the absorption state of the surface becomes a predetermined absorption state (the absorption state of the skin assumed in the calculation process) The light receiving unit 105 that receives light emitted from the surface of the skin whose short-time pulse light is backscattered by the skin and whose absorption state is adjusted is employed.

  The irradiation unit 104 irradiates the skin 31 with the short-time pulse light through the adjustment agent 120 in a state where the surface 104 a that irradiates the short-time pulse light is in contact with the adjustment agent 120. The light receiving unit 105 receives the light backscattered by the skin 31 through the adjustment agent 120 in a state where the surface 105 a that receives the light backscattered by the skin 31 is in contact with the adjustment agent 120.

  The absorption state of the surface of the skin 31 is adjusted by bringing the adjusting agent 120 that adjusts the absorption state into contact with the surface of the skin 31. The adjusting agent 120 is a liquid or gel-like member. As a method of adjusting the absorption state of the surface of the skin 31, a method of adjusting the external environment to a predetermined atmosphere (for example, an atmosphere having a predetermined humidity) may be employed.

  The adjusting agent 120 according to the present embodiment is a moisturizing agent that moisturizes the surface of the skin 31. For example, collagen is used as the adjusting agent 120. The adjusting agent 120 is not limited to this, and polymer materials, fatty liquids, soybean oil-whitened products, agar, black ink, and the like can also be used.

  Further, the absorption coefficient of the skin layer may change according to the change in the wavelength of the short-time pulsed light emitted by the irradiation unit 104. In this case, the adjusting agent 120 has an optical characteristic in which the value of the absorption coefficient of the skin layer that changes according to the change of the wavelength of the short-time pulse light irradiated by the irradiation unit 104 is close to the change of the actual absorption coefficient of the skin layer. It is preferable to use the material which has.

  FIG. 3 is a graph showing the spectral absorption coefficient in skin tissue. In FIG. 3, the horizontal axis indicates the wavelength of light, and the vertical axis indicates the absorption coefficient. The absorption coefficient of the dermis layer is the skin absorption coefficient measured by Troy et al., The absorption coefficient of the epidermis layer is 20% of the absorption coefficient of water, and the absorption coefficient of the subcutaneous tissue layer is the absorption coefficient of cholesterol.

As shown in FIG. 3, the absorption coefficient of each layer (skin layer, dermis layer, subcutaneous tissue layer) tends to increase as the wavelength of light increases, but has a peak (maximum value) at a certain wavelength. Focusing on the absorption coefficient at the peak of each layer, the absorption coefficient of the skin layer has a peak at a wavelength of 1450 nm and is about 0.6 mm ⁻¹ , and the absorption coefficient of the dermis layer has a peak at a wavelength of 1450 nm and has a peak of about 1.75 mm. ⁻¹ , the absorption coefficient of the subcutaneous tissue layer has a peak at a wavelength of 1750 nm and is about 1.2 mm ⁻¹ . The peak of the absorption coefficient of the skin layer is about 1/3 times the peak of the absorption coefficient of the dermis layer.

FIG. 4 is a schematic diagram showing an arrangement state of the adjusting agent 120.
In the present embodiment, as shown in FIG. 4, the adjusting agent 120 is applied to the surface of the skin 31 to adjust the absorption state of the surface of the skin 31. Then, the surfaces of the blood glucose level measuring apparatus 100 (the light irradiation surface 104a of the irradiation unit 104 and the light reception surface 105a of the light receiving unit 105 shown in FIG. 2) are brought into close contact with the surface of the skin 31 whose absorption state has been adjusted.

  The method for adjusting the absorption state of the surface of the skin 31 is not limited to this. For example, as shown in FIG. 5, the adjusting agent 120 may be disposed on the surface of the blood sugar level measuring apparatus 100. In this case, the blood sugar level measuring device 100 having the adjustment agent 120 disposed on the surface is brought into close contact with the surface of the skin 31.

  Returning to FIG. 2, in the blood glucose level measuring apparatus 100 according to the present embodiment, the irradiation unit 104 and the light receiving unit 105 are brought into close contact with the surface of the skin 31 via the adjusting agent 120, and the skin 31 is irradiated from the irradiation unit 104 in this tight contact state. The surface is irradiated with light R. The irradiated light R is scattered by the tissue in the skin 31 and diffuses into the skin 31. A part of the diffused light R reaches the light receiving unit 105 (backscattered light). The path through which the backscattered light reaching the light receiving unit 105 propagates in the skin 31 is a banana-shaped three-dimensional shape, that is, a so-called banana shape path.

  There is a certain relationship between the distance W between the light input and output between the irradiation unit 104 and the light receiving unit 105 and the penetration depth of the light R entering the skin 31. Therefore, the penetration depth of the light R that penetrates the skin 31 is uniquely determined by defining the distance W between the emission part 104 and the light reception part 105. For example, when the distance W between incident and outgoing is 10 mm, the penetration depth of the light R is 10 mm, and when the distance W between incoming and outgoing is 8 mm, the penetration depth of the light R is 8 mm.

FIG. 6 is a diagram showing the relationship between the wavelength of light and the penetration depth into the skin. In the figure, “Nd-YAG” is the wavelength of the laser beam output from the Nd-YAG laser, “Xe” is the wavelength of the laser beam output from the Xe laser, and “Cs” is the wavelength of the laser beam output from the Cs laser. “CO” represents the wavelength of the laser beam output from the carbon monoxide laser, and “CO ₂ ” represents the wavelength of the laser beam output from the carbon dioxide laser.
According to FIG. 6, it is understood that the laser light output from the Nd-YAG laser is suitable as the light sufficient to penetrate the dermis layer 33.

  Returning to FIG. 1, 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 from the optical path length distribution storage unit 102 the optical path length of each layer of the skin at a predetermined time of the optical path length distribution model. Here, the optical path length at a certain time is acquired from the optical path length distribution storage unit 102.

  The optical path length here refers to the length of the optical path from when the short-time pulse light irradiated from the irradiation unit 104 enters the skin and is scattered in the skin and detected by the light receiving unit 105. Yes, as will be described later, by setting the distance between the irradiation unit 104 and the light receiving unit 105, the optical path length of each layer of the skin is estimated.

  The non-absorptive light intensity acquisition unit 108 reads from the time-resolved waveform storage unit 103 when the light absorption coefficient at a predetermined time in the time-resolved waveform model of the short-time pulse light is zero (no absorption). Obtain a light intensity model. Here, the non-absorption light intensity at a certain time is acquired from the time-resolved waveform storage unit 103.

  The integration interval calculation unit 109 includes the light intensity distribution acquired by the measurement light intensity acquisition unit 106, the optical path length distribution acquired by the optical path length acquisition unit 107, and the non-absorption light intensity acquired by the non-absorption light intensity acquisition unit 108. Based on the above, an integration interval that is a time range (time width) of a region corresponding to the light intensity of each layer of the skin is calculated from the light intensity distribution.

Here, the integration interval is a time width of a region corresponding to the light intensity of an arbitrary layer in the light intensity distribution, and can be determined by the start time, the end time, and the increment time.
For example, (1) the light intensity output from the light receiving unit 105 that receives the backscattered light is detected with the light intensity equal to the minimum detection sensitivity from the time when the light intensity detected exceeds the minimum detection sensitivity of the measurement light intensity acquisition unit 106 Time to time, (2) time characteristics of non-absorbing light intensity acquired from the time-resolved waveform storage unit 103 storing the non-absorbing light intensity obtained by the simulation unit 101, and (3) a light receiving unit 105 in contact with the skin surface (4) The size of the skin model given to the simulation unit 101 and the optical characteristics (scattering coefficient, absorption coefficient, anisotropic parameter, or refractive index), the start time of the integration interval, Determine the end time and increment time.

The absorption coefficient calculation unit 110 is based on the time range of the region corresponding to the light intensity of the dermis layer (arbitrary layer) calculated by the integration interval calculation unit 109, for example, the start time, end time, and increment time of the integration interval. The absorption coefficient of glucose (target component) in the dermis layer (arbitrary layer) is calculated.
Here, the absorption coefficient and the estimated error rate of each layer of the skin 31 in the integration interval determined by the integration interval calculation unit 109 are obtained, and the distribution of the absorption coefficient and the estimated error rate of each layer of the skin 31 with respect to the integration interval is calculated.
In the absorption coefficient calculation unit 110, the absorption coefficient of each layer in the skin 31 is calculated from the following equation (4).

However, I (t) is the light intensity at time t of the model of the light intensity light receiving portion 105 has received at time t, N (t) is time-resolved waveform of the short pulse light having a specific wavelength λ _k, Li (t ) Is the optical path length of the i-th layer at time t in the model of the optical path length distribution in each layer of the skin, and μ i is the absorption coefficient of the i-th layer.
Here, the first layer is the epidermis layer, the second layer is the dermis layer, the third layer is the subcutaneous tissue layer, μ ₁ is the epidermal layer absorption coefficient, μ ₂ is the dermal layer absorption coefficient, and μ ₃ is the subcutaneous tissue. The absorption coefficient of the layer is indicated.

  The absorption coefficient distribution storage unit 111 stores the distribution of the absorption coefficient and estimated error rate of an arbitrary layer for the integration interval calculated by the absorption coefficient calculation unit 110. The absorption coefficient distribution storage unit 111 stores the absorption coefficient of each layer calculated based on the skin adjusted so that the absorption state of the surface becomes a predetermined absorption state.

  The absorption coefficient acquisition unit 112 uses the absorption coefficient and estimated error rate distribution of an arbitrary layer acquired from the absorption coefficient distribution storage unit 111, and a standard such as the range of the variation rate of the absorption coefficient with respect to the change of the integration interval, An absorption coefficient based on the glucose concentration corresponding to blood glucose in the skin main component of the layer at a specific depth from the surface of the skin is obtained.

The concentration calculation unit 113 calculates the concentration of glucose contained in the layer at the specific depth from the absorption coefficient based on the glucose concentration corresponding to blood glucose in the skin main component of the layer at the specific depth from the skin surface acquired by the absorption coefficient acquisition unit 112. Calculate the concentration.
The concentration calculation unit 113 calculates the concentration of glucose in an arbitrary layer of the skin from the following equation (5).

Where μa is the absorption coefficient in the a-th layer which is an arbitrary layer of the skin, gj is the molar concentration of the j-th component constituting the skin, εj is the absorption coefficient of the j-th component, and p is the number of main components constituting the skin , Q is the number of types of the specific wavelength λk.
Here, the first layer is the epidermis layer, the second layer is the dermis layer, the third layer is the subcutaneous tissue layer, μ ₁ is the epidermal layer absorption coefficient, μ ₂ is the dermal layer absorption coefficient, and μ ₃ is the subcutaneous tissue. The absorption coefficient of the layer is indicated.

  In the blood sugar level measuring apparatus 100, the irradiation unit 104 irradiates the skin 31 with the short-time pulse light via the adjustment agent 120 in a state where the surface 104 a for irradiating the short-time pulse light is in contact with the adjustment agent 120. The light receiving unit 105 receives the light backscattered by the skin 31 through the adjustment agent 120 in a state where the surface 105 a that receives the light backscattered by the skin 31 is in contact with the adjustment agent 120.

  When the light receiving unit 105 receives the back scattered light, the measurement light intensity acquisition unit 106 acquires the light intensity 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 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 stores the time-resolved waveform memory The intensity of light at time t of the time-resolved waveform of the short-time pulsed light in the skin model is acquired from the unit 103.

  Next, the integration interval calculation unit 109 includes the light intensity distribution acquired by the measurement light intensity acquisition unit 106, the optical path length distribution acquired by the optical path length acquisition unit 107, and the non-absorption time light acquired by the non-absorption time light intensity acquisition unit 108. Based on the intensity, an integration interval which is a time range (time width) of an area corresponding to the light intensity of each layer of the skin is calculated from the light intensity distribution.

  For example, (1) the light intensity output from the light receiving unit 105 that receives the backscattered light is detected with the light intensity equal to the minimum detection sensitivity from the time when the light intensity detected exceeds the minimum detection sensitivity of the measurement light intensity acquisition unit 106 Time to time, (2) time characteristics of non-absorbing light intensity acquired from the time-resolved waveform storage unit 103 storing the non-absorbing light intensity obtained by the simulation unit 101, and (3) a light receiving unit 105 in contact with the skin surface (4) The size of the skin model given to the simulation unit 101 and the optical characteristics (scattering coefficient, absorption coefficient, anisotropic parameter, or refractive index), the start time of the integration interval, Determine the end time and increment time.

Next, the absorption coefficient calculation unit 110 obtains the absorption coefficient and estimated error rate of an arbitrary layer in the integration interval determined by the integration interval calculation unit 109, and calculates the distribution of the absorption coefficient and estimated error rate of the arbitrary layer with respect to the integration interval. calculate.
Next, the absorption coefficient distribution storage unit 111 stores an absorption coefficient and an estimated error rate distribution of an arbitrary layer for the integration interval calculated by the absorption coefficient calculation unit 110. The absorption coefficient distribution storage unit 111 stores the absorption coefficient of each layer calculated based on the skin adjusted so that the absorption state of the surface becomes a predetermined absorption state.
Next, the absorption coefficient acquisition unit 112 has a standard such as the distribution of the absorption coefficient and estimated error rate of an arbitrary layer with respect to the integration interval acquired from the absorption coefficient distribution storage unit 111, and the range of the absorption coefficient variation rate with respect to the change of the integration interval. Is used to obtain an absorption coefficient based on the glucose concentration corresponding to blood glucose in the skin main component of the layer at a specific depth from the surface of the skin.

Next, the concentration calculation unit 113 specifies the skin surface based on the absorption coefficient based on the glucose concentration corresponding to blood glucose in the skin main component of the layer at the specific depth from the skin surface acquired by the absorption coefficient acquisition unit 112. The concentration of glucose contained in the layer at the depth is calculated based on the above equation (5).
Thereby, the influence of the noise by layers other than the layer of specific depth can be reduced, and the concentration of glucose contained in the layer of specific depth can be calculated.

Next, the operation of the blood sugar level measuring apparatus 100 will be described.
When the glucose level in the dermis layer 33 shown in FIG. 2 is measured by the blood glucose level measuring apparatus 100, the optical path length distribution and the time-resolved waveform in each layer of the skin model are calculated in advance before measuring the blood glucose level. There is a need.

Here, a method for calculating the 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, absorption coefficient, and thickness of each layer of the skin. Here, if the skin portion is specified, the scattering coefficient and thickness of each layer in the specified skin portion may be determined by taking a sample in advance. The thickness of the epidermis layer 32 is approximately 0.3 mm, the thickness of the dermis layer 33 is approximately 1.2 mm, and the thickness of the subcutaneous tissue layer 34 is approximately 3.0 mm.
The absorption coefficient of the skin model used here is zero. The reason is that the amount of light absorption is calculated using this skin model.

When the simulation unit 101 generates a 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 performed using, for example, a Monte Carlo method.
The simulation by the Monte Carlo method is performed as follows, for example.

  First, the simulation unit 101 uses a model of light to be irradiated as a photon (light beam), and performs calculation to irradiate the skin model with the photon. 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 at which the photon advances next using Equation (6).

  Here, μs represents the scattering coefficient of the s-th layer (any one of the epidermis layer, dermis layer, and 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 (7).

  However, g shows the anisotropic parameter which is the average of 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 (6) and (7) 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. 7 is a diagram illustrating the optical path length distribution of each layer calculated by the simulation unit.
In FIG. 7, the horizontal axis represents the elapsed time from the photon irradiation, and the vertical axis represents 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. And the simulation part 101 calculates the optical path length distribution of each layer of skin as shown in FIG. 7 by calculating the average length of the movement path | route of the photon which arrived for every unit time for every classified layer.

  Moreover, the simulation part 101 calculates the time-resolved waveform of a skin model as shown in FIG. 8 by calculating the number of photons that have reached the light-receiving part 105 every unit time.

  FIG. 8 is a diagram illustrating a time-resolved waveform of the non-absorbing light intensity (equal to the number of received photons) N (t) obtained by the simulation unit 101. In FIG. 8, the horizontal axis represents the elapsed time from photon irradiation, and the vertical axis represents the number of photons detected by the light receiving unit 105.

  Through the processing as described above, the simulation unit 101 calculates the 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 an optical path length distribution and a time-resolved waveform for a wavelength having a large difference in absorption spectrum of skin main components (water, protein, lipid, glucose, etc.).

FIG. 9 is a graph showing the absorption spectrum of the main component of the skin. In FIG. 9, the horizontal axis represents the wavelength of light to be irradiated, and the vertical axis represents the absorption coefficient.
FIG. 9 shows that the absorption coefficient of glucose is maximized when the wavelength is 1600 nm, and the absorption coefficient of water is maximized when the wavelength is 1450 nm.
Therefore, the simulation unit 101 may calculate the optical path length distribution and the time-resolved waveform for wavelengths having a large 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 optical path length distribution and time-resolved waveform of the skin model corresponding to a plurality of wavelengths, the optical path length distribution storage unit 102 stores information on the calculated optical path length distribution, and the time-resolved waveform storage unit 103 Stores information of the calculated time-resolved waveform.

  Next, a procedure for measuring a blood glucose level using the blood glucose level measuring apparatus 100 will be described with reference to FIGS.

  First, the person to be measured applies the blood glucose level measuring device 100 to the skin 31 such as a wrist as shown in FIG. In the present embodiment, as shown in FIG. 4, the adjustment agent 120 is applied in advance to the surface of the skin 31 to adjust the absorption state of the surface of the skin 31. Thereby, the surface (the light irradiation surface 104a of the irradiation part 104, and the light-receiving surface 105a of the light-receiving part 105) of the blood glucose level measuring apparatus 100 is closely_contact | adhered to the surface of the skin 31 in which the absorption state was adjusted.

Then, the blood glucose level measuring apparatus 100 is operated by pressing a measurement start switch (not shown) or the like. Then, the irradiation unit 104 in a state where the light irradiation surface 104a is in contact with the modifier 120, via the reconciliation agent 120 is irradiated with short pulse light having a wavelength lambda _k to the skin 31 (step S1).

As the wavelength λ _k , for example, one of a plurality of wavelengths for which the simulation unit 101 has calculated the optical path length distribution and the time-resolved waveform is preferable.
For example, among the main components constituting the skin 31, light having a wavelength at which the absorption coefficient of a specific component in one main component is larger than the absorption coefficient of another component, that is, the minimum value of the absorption coefficient of the specific component is the other component. It is preferable to calculate the optical path length distribution and the time-resolved waveform for light having a wavelength significantly different from the minimum value of the absorption coefficient.

When the irradiation unit 104 irradiates the short pulse light having a wavelength lambda _k, the light receiving unit 105 backward while the light receiving surface 105a is in contact with the modifier 120, the skin 31 is irradiated from the irradiation unit 104 via the reconciliation agent 120 The scattered light is received (step S2).

At this time, the light receiving unit 105 records the received light intensity for each unit time from the start of irradiation (for example, times t _{1 to} t _m every 1 picosecond) in an internal memory (not shown).

Next, based on the photon arrival time from each layer, the absorption interval of the dermis layer 33 is calculated by changing the integration interval (processing A; step S3).
This step S3 is performed by the operation shown in FIG.

  The integration interval calculation unit 109 includes the light intensity distribution acquired by the measurement light intensity acquisition unit 106, the optical path length distribution acquired by the optical path length acquisition unit 107, and the non-absorption light intensity acquired by the non-absorption light intensity acquisition unit 108. Based on the above, an integration interval that is a time range (time width) of a region corresponding to the light intensity of each layer of the skin is calculated from the light intensity distribution.

Here, the minimum detection sensitivity from the time when the light intensity output from the light receiving unit 105 that receives the backscattered light by the integration interval calculation unit 109 exceeds the minimum detection sensitivity of the measurement light intensity acquisition unit 106 is detected. (2) the time characteristic of the non-absorbing light intensity acquired from the time-resolved waveform storage unit 103 storing the non-absorbing light intensity obtained by the simulation unit 101, (3) ) Using the distance between the light receiving unit 105 and the irradiation unit 104 in contact with the skin surface, and (4) the size and optical characteristics (scattering coefficient, absorption coefficient, anisotropic parameter, or refractive index) of the skin model given to the simulation unit 101 To calculate the integration interval.
More specifically, the start time, end time, and increment time of the integration interval are calculated (step S11).

  When the light receiving unit 105 completes the light reception, the measurement light intensity acquisition unit 106 acquires the received light intensity at a certain time t as many as the number of different skin models from the received light intensity recorded in the internal memory ( Step S12).

For example, when concentration measurement is performed using three types of wavelengths for three layers of skin as a plurality of different skin models, the received light intensity I (t ₁ ) to I (I) at _three different times t _{1 to} t ₃ t ₃₎ to get. 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.

In addition, the times t ₁ to t _{3 at} which the measurement light intensity acquisition unit 106 acquires the light intensity may be a time at which the optical path length distribution of each layer of the skin becomes a peak. That is, the light intensity at the time obtained by adding the time when the optical path length of each layer of the skin 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 optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 102. time _t 1 the optical path length of each layer of the skin at _{~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 S13).

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 the decomposition waveform, the light intensity at a predetermined time of a plurality of skin models having different time-resolved waveforms of the short-time pulsed light, for example, the number of detected photons at the time t _{1 to} t ₃ (light intensity at non-absorption) N (t ₁ ) to N (t ₃ ) is acquired (step S14).

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 number of detected photons (non-absorption light intensity) N (t ₁ ) to N (t ₃ ), the absorption coefficient The calculation unit 110 calculates the absorption coefficients μ _{1 to} μ ₃ of each layer of the skin in a certain integration interval calculated by the integration interval calculation unit 109 based on Expression (8) (step S15).
Here, the absorption coefficient μ ₁ indicates the absorption coefficient of the epidermis layer, the absorption coefficient μ ₂ indicates the absorption coefficient of the dermis layer, and the absorption coefficient μ ₃ indicates the absorption coefficient of the subcutaneous tissue layer.

N (t) represents the light intensity at time t of the model of the time-resolved waveform of the short-time pulsed light with the specific wavelength λk. 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 absorption coefficient calculation unit 110 calculates the absorption coefficient μ _{1 to} μ ₃ of each layer of the skin in an integration interval, the absorption coefficient distribution storage unit 111 calculates the skin coefficient in a certain integration interval calculated by the absorption coefficient calculation unit 110. The absorption coefficients μ _{1 to} μ ₃ of each layer are stored (step S16). The absorption coefficient distribution storage unit 111 stores the absorption coefficient of each layer calculated based on the skin adjusted so that the absorption state of the surface becomes a predetermined absorption state.

When the absorption coefficient calculation unit 110 calculates the absorption coefficient μ _{1 to} μ ₃ of each skin layer in an integration interval, the absorption coefficient calculation unit 110 has calculated whether or not the absorption coefficient of the dermis layer in the set integration interval has been calculated. Is determined (step S17).

In this embodiment, blood sugar levels are measured with four main components of skin, water, protein, lipid, and glucose, so that the absorption coefficient calculation unit 110 absorbs the four wavelengths λ _{1 to} λ ₄ . It is determined whether 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 optical path length distribution and the time-resolved waveform.

Here, when it is determined that there is an absorption coefficient that is not calculated in the absorption coefficient μ _{1 to} μ ₃ of the dermis layer in the integration interval set by the absorption coefficient calculation unit 110 (step S17: NO), again at a certain time. Returning to the acquisition of the received light intensity (step S12), the absorption coefficient of the dermis layer that has not been calculated yet is calculated, and it is determined again whether or not the absorption coefficient of the dermis layer can be calculated in the set integration interval (step S17). .

On the other hand, when it is determined that the absorption coefficient μ _{1 to} μ ₃ of the dermis layer has been calculated in the integration interval set by the absorption coefficient calculation unit 110 (step S17: YES), the absorption coefficient is acquired from the absorption coefficient distribution of the dermis layer. (Step S18).

  Returning to FIG. 10, the absorption coefficient acquisition unit 112 determines whether or not the absorption coefficient of the number of wavelengths corresponding to the number of types of main components of the skin has been calculated (step S4).

  Here, when it is determined that the absorption coefficient acquisition unit 112 has not calculated the absorption coefficient of the number of wavelengths corresponding to the number of main components of the skin (step S4: NO), irradiation with short-time pulsed light (step S1) Returning to step S4, the absorption coefficient of the number of wavelengths corresponding to the number of types of principal components of the skin that have not been calculated yet is calculated, and it is determined again whether the absorption coefficient can be calculated (step S4).

  On the other hand, when it is determined that the absorption coefficient acquisition unit 112 has calculated the absorption coefficient of the number of wavelengths corresponding to the number of types of the main component of the skin (step S4: YES), the concentration calculation unit 113 determines the concentration of glucose contained in the dermis layer. Is calculated (step S5).

  The concentration calculation unit 113 calculates the concentration of glucose in the dermis layer based on the following equation (9).

_{However, μ 2 (1) ~μ 2} (4) shows the 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 (9), the molar concentration of glucose contained in the dermis layer can be obtained.

The reason why the molar concentration of glucose can be determined by equation (9) will be described.
Since the wavelength dependence of the skin scattering coefficient is small, changes in the number of detected photons N (t) and the optical path length Ln (t) with respect to the wavelength can be ignored. Further, it can be expressed by Absorption coefficient = Molar extinction coefficient × Molar concentration according to the Beer-Lambert law. Thus, by eliminating the detected photon number N (t) from time-resolved measurement obtained at two wavelengths, the relational expression between the absorption coefficient difference obtained in the dermis layer and the molar absorption coefficient of each component forming the skin Equation (9) showing can be derived.

The blood glucose level measuring apparatus 100 described above has a built-in computer system therein, and the processing operation of each step described above is stored in a computer-readable recording medium in the form of a program. Therefore, the computer can read out and execute this program to perform the above processing operation.
Here, examples of the computer-readable recording medium include a magnetic disk, a magneto-optical disk, a CD-ROM, a DVD-ROM, and a semiconductor memory.
Further, 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.
Furthermore, what can implement | achieve the function mentioned above in combination with the program already recorded on the computer system, what is called a difference file (difference program) may be sufficient.

According to the configuration of the present embodiment, the absorption coefficient of an arbitrary layer can be selectively calculated from the time-resolved waveform of received light. Therefore, by calculating the concentration of the target component based on the calculated absorption coefficient, it is possible to reduce the influence of noise due to the other layers and perform highly accurate concentration quantification.
Here, in the process (calculation process) in which the absorption coefficient calculation unit calculates the absorption coefficient, it is not assumed that extra absorption other than the target component occurs in the observation target. However, the actual skin surface condition varies depending on the external environment (for example, dryness, wetness, etc.) and individual differences (for example, age, sex, etc.). For this reason, the skin surface state assumed in the calculation process may be different from the skin surface state when actually measuring the concentration of the target component in an arbitrary layer to be observed. If the configuration is such that the light emitted from the irradiator directly enters the skin surface, the concentration of the target component in any layer to be observed can be accurately measured based on changes in the skin surface properties due to the external environment or individual differences. Can not do it.

  FIG. 12 is a diagram showing the relationship between the absorption coefficient and the integration interval in the dermis layer. In FIG. 12, a three-layer skin model of the epidermis layer, the dermis layer, and the subcutaneous tissue layer is used, and the absorption coefficient of the epidermis layer varies by −90% to + 150% with respect to the literature value with respect to the absorption coefficient of the dermis layer. It shows the relationship between the integration interval and the absorption coefficient of the dermis layer. In FIG. 12, A is −90%, B is −50%, C is ± 0%, D is + 50%, E is + 100%, F is + 150%, and G is + 200%. Show.

  FIG. 13 is a diagram showing the relationship between the estimated error rate of the absorption coefficient in the dermis layer and the integration interval. In FIG. 13, a three-layer skin model of the epidermis layer, the dermis layer, and the subcutaneous tissue layer is used. This shows the relationship between the integration interval and the estimated error rate of the absorption coefficient of the dermal layer. In FIG. 13, A is −90%, B is −50%, C is ± 0%, D is + 50%, E is + 100%, F is + 150%, and G is + 200%. Show.

  As shown in FIGS. 12 and 13, when the absorption coefficient of the epidermis layer is changed, the calculated value of the absorption coefficient in an arbitrary layer of the skin varies. Thereby, the characteristic of the absorption coefficient of a different dermis layer is calculated by changing an integration area. Therefore, the concentration of the target component in any layer of the skin calculated based on different absorption coefficients will also be different.

  On the other hand, in the present embodiment, the concentration of the target component in an arbitrary layer to be observed is measured in a state where the absorption state on the surface of the observation target is adjusted to a predetermined absorption state. For this reason, it is possible to avoid variation in the calculated value of the absorption coefficient in any layer of the skin due to changes in the properties of the skin surface due to the external environment and individual differences during actual measurement. Therefore, the concentration of the target component in an arbitrary layer to be observed can be calculated with high accuracy.

  As a method of adjusting the absorption state of the surface to be observed, a method of adjusting the external environment to a predetermined atmosphere is also conceivable, but this requires a large-scale facility. On the other hand, according to this configuration, the absorption state of the surface of the observation target can be adjusted by a simple method of bringing the adjusting agent 120 into contact with the surface of the observation target. Therefore, it becomes easy to calculate the concentration of the target component in any layer to be observed with high accuracy.

  Further, according to this configuration, since the adjusting agent 120 is a liquid or gel-like member, the absorption state of the surface of the observation target can be determined by a simple method (for example, a method of applying the adjusting agent to the surface of the observation target). Can be adjusted. Therefore, it becomes easy to calculate the concentration of the target component in any layer to be observed with high accuracy.

  Further, according to this configuration, the adjusting agent 120 is filled between the light irradiation surface 104a of the irradiation unit 104 and the light reception surface 105a of the light receiving unit 105 and the observation target, so that there is no influence of interface reflection or the like, and more disturbance. It becomes possible to suppress the influence of.

Further, according to this configuration, the measurement light intensity acquisition unit 106 acquires the light intensity at a plurality of times t _{1 to} t _m of an arbitrary layer, and the absorption coefficient calculation unit 110 calculates the absorption coefficient of the arbitrary layer. It calculates from said Formula (4).
In this way, by measuring the time-resolved backscattered light, backscattered light from layers other than any layer can be reduced as noise, and the influence of the layer other than any layer on the concentration of the target component can be reduced. Can be reduced. Therefore, the concentration of the target component can be measured with higher accuracy.

Moreover, according to this structure, the irradiation part 104 irradiates the light of the several wavelengths 1-q, and the absorption coefficient calculation part 110 is the absorption coefficient in arbitrary layers for every several wavelength which the irradiation part 104 irradiated. The concentration calculation unit 113 calculates the concentration of the target component in an arbitrary layer from the above equation (5).
In this way, by measuring the time-resolved backscattered light, backscattered light from layers other than any layer can be reduced as noise, and the influence of the layer other than any layer on the concentration of the target component can be reduced. Can be reduced. Therefore, the concentration of the target component can be measured with higher accuracy.

  Moreover, according to this structure, since the adjustment agent 120 covers the surface of skin, it can maintain in the state by which the keratin | lamination laminated state in the outermost surface was maintained. For this reason, even if the number of wrinkles increases due to the change in the skin surface properties due to changes in the external environment or individual skin, the skin absorption coefficient of the epidermis assumed in the calculation process is increased. It is possible to make the skin surface state coincide with the skin surface state of the absorption coefficient of the epidermis when the concentration of the target component in an arbitrary layer to be observed is actually measured. Therefore, the concentration of the target component in an arbitrary layer to be observed can be calculated with high accuracy.

  In addition, by disposing the adjustment agent 120 on the surface of the skin, it is possible to prevent the interstitial fluid ((interstitial fluid) water) in the dermis layer from being supplied to the epidermis layer and evaporating. Further, as shown in FIG. 9, this water absorption coefficient has an absorption peak in the vicinity of 1450 nm, which affects the accuracy in determining the glucose concentration. Therefore, by maintaining the water content of the epidermis layer constant, it is possible to ensure the accuracy in obtaining the glucose concentration.

  In addition, according to this configuration, by calculating the concentration of glucose contained in the dermis layer based on the calculated absorption coefficient, the influence of noise by other layers is reduced, and the glucose concentration is quantified with high accuracy. be able to.

  In the present embodiment, the skin that has been adjusted so that the absorption state of the surface is the absorption state assumed when calculating the model of the optical path length distribution and the model of the time-resolved waveform is irradiated with the short-time pulsed light. Although described with reference to the configuration including the irradiation unit 104 and the light receiving unit 105 that receives the light emitted from the surface of the skin whose short-time pulsed light is backscattered by the skin and whose absorption state is adjusted, Not exclusively.

  For example, an irradiation unit that irradiates a skin with a short-time pulse light on a skin whose surface scattering state is adjusted to a scattering state assumed when calculating a model of an optical path length distribution and a model of a time-resolved waveform, and a short-time pulse light And a light receiving unit that receives light emitted from the surface of the skin that is backscattered and adjusted in the scattering state. In other words, in addition to the configuration in which the absorption state of the skin surface is adjusted by bringing the adjustment agent (so-called absorption layer) that adjusts the absorption state into contact with the skin surface, the scattering state of the skin surface is scattered on the skin surface. You may provide the structure adjusted by making the adjusting agent (what is called a scattering layer) which adjusts a state contact.

  For example, as the adjusting agent for adjusting the scattering state of the skin surface, a moisturizing agent (for example, collagen) that moisturizes the skin surface can be used in the same manner as the adjusting agent for adjusting the absorption state of the skin surface. In this case, as the adjusting agent, the value of the scattering coefficient and absorption coefficient of the skin layer that changes in accordance with the change of the wavelength of the short-time pulsed light irradiated by the irradiation unit changes the scattering coefficient and absorption coefficient of the actual skin layer. It is preferable to use a material having close optical properties.

  As a result, the concentration of the target component in any layer of the skin is measured with the scattering state of the skin surface adjusted to the scattering state assumed when calculating the optical path length distribution model and the time-resolved waveform model. can do. As a result, there is almost no difference between the optical path length distribution model and the time-resolved waveform model calculated by the simulation and the optical path length distribution model and the time-resolved waveform model at the time of actual measurement. For this reason, it is possible to avoid changes in the properties of the skin surface due to the external environment and individual differences between the simulation and the actual measurement. Therefore, the concentration of the target component in any layer of the skin can be calculated with high accuracy.

  In the present embodiment, an example is described in which a conditioner is applied to the skin surface to adjust the absorption state of the skin surface. However, the present invention is not limited thereto. For example, a sheet-like member (layered member) may be arranged on the skin surface as an adjusting agent to adjust the absorption state of the skin surface.

  In addition, as a material for obtaining an absorption coefficient at a desired light wavelength for glucose concentration measurement, a nanometer-sized component having an overall size of several micrometers can be used. For example, the nanometer size composition includes a gold nanoparticle composition composed of gold nanoparticles and an organic ligand molecule composed of an organic substance bonded to the gold nanoparticle, a composition such as a carbon nanotube wire having a size of 100 nm or less. .

(Second Embodiment)
14 and 15 are flowcharts showing the operation of the blood sugar level measuring apparatus (concentration quantifying apparatus) according to the second embodiment of the present invention measuring the blood sugar level.
The blood sugar level measuring apparatus of the present embodiment has the same configuration as the blood sugar level measuring apparatus 100 of the first embodiment, and includes an optical path length acquisition unit 107, a non-absorption light intensity acquisition unit 108, a measured light intensity acquisition unit 106, and an absorption coefficient. The operation of the calculation unit 110 is different.

Next, a procedure for measuring a blood sugar level using the blood sugar level measuring apparatus 100 will be described.
In the present embodiment, “the irradiation unit 104 irradiates the skin 31 with a short-time pulsed light having a wavelength λ _k through the adjustment agent 120 in a state where the light irradiation surface 104a is in contact with the adjustment agent 120” (step S21). ) To “The light receiving unit 105 receives light emitted from the irradiation unit 104 via the adjusting agent 120 and back-scattered by the skin 31 with the light receiving surface 105a in contact with the adjusting agent 120” (step S22). Since it is the same as the procedure of 1st Embodiment, description is abbreviate | omitted.

Based on the photon arrival time from each layer, the integration interval is changed to calculate the absorption coefficient of the dermis layer 33 (process B; step S23).
This step S23 is performed by the operation shown in FIG.

  First, the integration interval calculation unit 109 (1) determines the minimum detection sensitivity from the time when the light intensity output from the light receiving unit 105 that receives the backscattered light exceeds the minimum detection sensitivity of the measurement light intensity acquisition unit 106. Time until time detected with equal light intensity, (2) time characteristics of non-absorbing light intensity acquired from the time-resolved waveform storage unit 103 storing the non-absorbing light intensity obtained by the simulation unit 101, (3) Using the distance between the light receiving unit 105 and the irradiation unit 104 in contact with the skin surface, and (4) the size and optical characteristics (scattering coefficient, absorption coefficient, anisotropic parameter, or refractive index) of the skin model given to the simulation unit 101 Calculate the integration interval. More specifically, the start time, end time, and increment time of the integration interval are calculated (step S31).

  Next, 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 recorded in the internal memory (step S32). .

For example, when concentration measurement is performed for three layers of skin using four types of wavelengths, time distributions of received light intensity at _three different times τ _{1 to} τ ₃ are acquired.

When the measurement light intensity acquisition unit 106 acquires the time distribution of the received light intensity during the time τ, the optical path length acquisition unit 107 starts from the optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 102 from a certain time. The optical path length of each layer of the skin during time τ, for example, optical path lengths L ₁ (t ₁ ) to L ₁ (t ₃ ), L ₂ (t ₁ ) to L ₂ (t ₃ ), L ₃ (t ₁ ) ~L ₃ acquires _{(t 3)} (step S33).

When the measurement light intensity acquisition unit 106 acquires the time distribution of the received light intensity during the time τ, the non-absorption light intensity acquisition unit 108 uses the time-resolved waveform of the wavelength λ ₁ stored in the time-resolved waveform storage unit 103. The non-absorption light intensity between a certain time and the time τ, for example, the number of detected photons (non-absorption light intensity) N (t ₁ ) to N (t ₃ ) between the certain time and the time τ is acquired (step S34). ).

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 number of detected photons (non-absorption light intensity) N (t ₁ ) to N (t ₃ ), the absorption coefficient The calculation unit 110 calculates the absorption coefficients μ _{1 to} μ ₃ of each layer of the skin in a certain integration interval calculated by the integration interval calculation unit 109 based on the formula (10) (step S35).
Here, the absorption coefficient μ ₁ indicates the absorption coefficient of the epidermis layer, the absorption coefficient μ ₂ indicates the absorption coefficient of the dermis layer, and the absorption coefficient μ ₃ indicates the absorption coefficient of the subcutaneous tissue layer.

Here, I (t) indicates the light receiving intensity of the light receiving unit 105 at time t. I _in indicates the light intensity of the short-time pulse light irradiated by the irradiation unit 104. N _in indicates the number of photons for which the simulation unit 101 has simulated irradiation. L ₁ (t ₁ ) to L ₁ (t ₃ ) indicate the optical path length of each layer of the skin at time t.

When the absorption coefficient calculation unit 110 calculates the absorption coefficient μ _{1 to} μ ₃ of each layer of the skin in an integration interval, the absorption coefficient distribution storage unit 111 calculates the skin coefficient in a certain integration interval calculated by the absorption coefficient calculation unit 110. The absorption coefficients μ _{1 to} μ ₃ of each layer are stored (step S36). The absorption coefficient distribution storage unit 111 stores the absorption coefficient of each layer calculated based on the skin adjusted so that the absorption state of the surface becomes a predetermined absorption state.

When the absorption coefficient calculation unit 110 calculates the absorption coefficient μ _{1 to} μ ₃ of each skin layer in an integration interval, the absorption coefficient calculation unit 110 has calculated whether or not the absorption coefficient of the dermis layer in the set integration interval has been calculated. Is determined (step S37).

In this embodiment, blood sugar levels are measured with four main components of skin, water, protein, lipid, and glucose, so that the absorption coefficient calculation unit 110 absorbs the four wavelengths λ _{1 to} λ ₄ . It is determined whether 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 optical path length distribution and the time-resolved waveform.

Here, when it is determined that there is an absorption coefficient that has not been calculated in the absorption coefficient μ _{1 to} μ ₃ of the dermis layer in the integration interval set by the absorption coefficient calculation unit 110 (step S37: NO), again at a certain time. Returning to the acquisition of the received light intensity (step S32), the absorption coefficient of the dermis layer that has not been calculated yet is calculated, and it is determined again whether or not the absorption coefficient of the dermis layer can be calculated in the set integration interval (step S37). .

On the other hand, when it is determined that the absorption coefficient μ _{1 to} μ ₃ of the dermis layer in the integration interval set by the absorption coefficient calculation unit 110 has been calculated (step S37: YES), the absorption coefficient is acquired from the absorption coefficient distribution of the dermis layer. (Step S38).

  Returning to FIG. 14, the absorption coefficient acquisition unit 112 determines whether or not the absorption coefficient of the number of wavelengths corresponding to the number of types of the main components of the skin has been calculated (step S24).

  Here, when it is determined that the absorption coefficient acquisition unit 112 has not calculated the absorption coefficient of the number of wavelengths corresponding to the number of types of main components of the skin (step S24: NO), irradiation with short-time pulsed light (step S21) Returning to step S24, the absorption coefficient of the number of wavelengths corresponding to the number of types of principal components of the skin that have not been calculated yet is calculated, and it is determined again whether the absorption coefficient can be calculated (step S24).

  On the other hand, when it is determined that the absorption coefficient acquisition unit 112 has calculated the absorption coefficient of the number of wavelengths corresponding to the number of types of skin main components (step S24: YES), the concentration calculation unit 113 determines the concentration of glucose contained in the dermis layer. Is calculated (step S25).

Thus, according to the present embodiment, the measurement light intensity acquisition unit 106 acquires a temporal change in light intensity between a predetermined time and at least a predetermined time τ, and the absorption coefficient calculation unit 110 performs an arbitrary layer. Is calculated from the above equation (10).
In this way, by measuring the time-resolved backscattered light, backscattered light from layers other than any layer can be reduced as noise, and the influence of the layer other than any layer on the concentration of the target component can be reduced. Can be reduced. Therefore, the concentration of the target component can be measured with higher accuracy.

As described above, each 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 can be made without departing from the scope of the present invention. Etc. are possible.
For example, in the first embodiment and the second embodiment, by taking a blood sugar level measuring device as a concentration quantification device, palm skin as an observation target, glucose as a target component, and short-time pulsed light as pulsed light, respectively. Although the case where the concentration of glucose contained in the dermis layer of the skin is measured has been described, the present invention is not limited to this. For example, the concentration determination method may be used for another apparatus for determining the concentration of a target component in an arbitrary observation target layer formed from a plurality of light scattering medium layers. You may change to continuous light of a specific wavelength.
For example, when it is applied to a portable skin main component concentration measuring apparatus, it can be effectively used for examination, diagnosis, treatment, etc. of skin diseases.

DESCRIPTION OF SYMBOLS 31 ... Skin (observation object), 33 ... Dermal layer (arbitrary layer), 100 ... Blood glucose level measuring device (concentration determination device), 102 ... Optical path length distribution storage unit, 103 ... Time-resolved waveform storage unit, 104 ... Irradiation unit , 104a... Light irradiation surface (surface that emits short-time pulse light), 105... Light receiving portion, 105 a... Light receiving surface (surface that receives backscattered light), 106 ... measurement light intensity acquisition portion (light intensity acquisition portion) DESCRIPTION OF SYMBOLS 107 ... Optical path length acquisition part 108 ... Non-absorption light intensity acquisition part (light intensity model acquisition part) 110 ... Absorption coefficient calculation part 113 ... Concentration calculation part 120 ... Adjuster

Claims (11)

A concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of a plurality of layers,
An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers of short-time pulse light irradiated to the observation target;
A time-resolved waveform storage unit that stores a model of a time-resolved waveform of the short-time pulsed light that irradiates the observation target;
An irradiating unit that irradiates the observation target for a short time with the observation target adjusted so that the absorption state of the surface becomes a predetermined absorption state;
A light receiving unit that receives the light emitted from the surface of the observation target in which the short-time pulsed light is backscattered by the observation target and the absorption state is adjusted;
A light intensity acquisition unit that acquires the intensity of light received by the light receiving unit at a predetermined time after the time when the irradiation unit irradiated pulsed light for a short time;
An optical path length acquisition unit that acquires an optical path length of each of the plurality of layers at the predetermined time of the optical path length distribution model from the optical path length distribution storage unit;
A light intensity model acquisition unit that acquires a light intensity model at the predetermined time of the model of the time-resolved waveform of the short-time pulsed light from the time-resolved waveform storage unit;
The light intensity acquired by the light intensity acquisition unit, the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light intensity model acquired by the light intensity model acquisition unit Based on the absorption coefficient calculation unit for calculating the absorption coefficient of the arbitrary layer,
Based on the absorption coefficient calculated by the absorption coefficient calculation unit, a concentration calculation unit that calculates the concentration of the target component in the arbitrary layer;
Concentration determination device including   The concentration quantification apparatus according to claim 1, wherein the absorption state of the surface of the observation target is adjusted by bringing a regulator that adjusts the absorption state into contact with the surface of the observation target.   The concentration quantification apparatus according to claim 1, wherein the adjusting agent is a liquid or gel-like member. The irradiation unit irradiates the observation target with the short-time pulsed light through the adjusting agent in a state where the surface to be irradiated with the short-time pulsed light is in contact with the adjusting agent,
The light receiving unit receives the light backscattered by the observation target via the adjustment agent in a state where a surface receiving light scattered by the observation target is in contact with the adjustment agent. The concentration determination apparatus according to any one of the above. The light intensity acquisition unit acquires light intensities 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 (where n is a natural number of 1 or more, m is a natural number of n or more),
The absorption coefficient calculation unit includes I (t) indicating the light intensity received by the light receiving unit at time t, N (t) indicating the light intensity at time t of the model of the time-resolved waveform of the short-time pulsed light, Using Li (t) indicating the optical path length of the i-th layer at time t in the optical path length distribution model and μ _i indicating the absorption coefficient of the i-th layer, the absorption coefficient of an arbitrary layer can be calculated from the following equation (1). The concentration determination apparatus according to claim 1, wherein the concentration determination apparatus calculates the concentration determination apparatus according to claim 1.

The light intensity acquisition unit acquires a light intensity during a predetermined time τ from a predetermined time,
The absorption coefficient calculation unit includes I (t) indicating the light intensity received by the light receiving unit at time t, N (t) indicating the light intensity at time t of the model of the time-resolved waveform of the short-time pulsed light, Using Li (t) indicating the optical path length of the i-th layer at time t in the optical path length distribution model, n indicating the number of layers to be observed, and μi indicating the absorption coefficient of the i-th layer, the following formula ( The concentration quantification apparatus according to any one of claims 1 to 4, wherein an absorption coefficient of an arbitrary layer is calculated from 2).

The irradiation unit irradiates light having a plurality of wavelengths 1 to q,
The absorption coefficient calculation unit calculates an absorption coefficient in the arbitrary layer for each of a plurality of wavelengths irradiated by the irradiation unit,
The concentration calculator
Μa (i) indicating the absorption coefficient of the wavelength i in the a-layer which is the arbitrary layer, gj indicating the molar concentration of the j-th component forming the observation object, and ε indicating the absorption coefficient of the j-th component with respect to the wavelength i _{j (i)} , p indicating the number of main components forming the observation object, and q indicating the number of types of wavelengths irradiated by the irradiation unit, the target component in the arbitrary layer from the following equation (3) The concentration quantification apparatus according to claim 1, wherein the concentration is calculated.

  The concentration quantification apparatus according to any one of claims 1 to 7, wherein the observation target is skin, and the adjusting agent is a moisturizing agent that moisturizes the surface of the skin.   The concentration quantification apparatus according to any one of claims 1 to 8, wherein the observation target is skin, the arbitrary layer is a dermis layer, and the target component is glucose. An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers of short-time pulse light irradiated to the observation target configured by a plurality of layers; A concentration quantification method using a concentration quantification device comprising a time-resolved waveform storage unit for storing a model of a time-resolved waveform of the short-time pulse light to be irradiated, and quantifying a concentration of a target component in an arbitrary layer of the observation target Because
The irradiation unit irradiates the observation target adjusted so that the absorption state of the surface becomes a predetermined absorption state with a short-time pulse light,
The light receiving unit receives the light emitted from the surface of the observation target in which the short-time pulse light is backscattered by the observation target and the absorption state is adjusted,
The light intensity acquisition unit acquires the intensity of light received by the light receiving unit at a predetermined time after the time when the irradiation unit irradiated the short-time pulsed light,
The optical path length acquisition unit acquires an optical path length of each of the plurality of layers at the predetermined time of the optical path length distribution model from the optical path length distribution storage unit,
The light intensity model acquisition unit acquires the light intensity model at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage unit,
The absorption coefficient calculation unit acquires the light intensity acquired by the light intensity acquisition unit, the optical path length of each of the plurality of layers acquired by the optical path length acquisition unit, and the light intensity model acquisition unit acquired Based on the light intensity model, calculate the absorption coefficient of the arbitrary layer,
The concentration calculation unit calculates the concentration of the target component in the arbitrary layer based on the absorption coefficient calculated by the absorption coefficient calculation unit.
Concentration determination method. An optical path length distribution storage unit for storing a model of an optical path length distribution in each of the plurality of layers of short-time pulse light irradiated to the observation target configured by a plurality of layers; A time-resolved waveform storage unit that stores a model of a time-resolved waveform of the short-time pulse light to be irradiated, and a computer for a concentration quantification device that quantifies the concentration of a target component in an arbitrary layer of the observation target,
An irradiation procedure for irradiating the observation target with a short-time pulsed light adjusted so that the surface absorption state is a predetermined absorption state,
A light receiving procedure for receiving light emitted from the surface of the observation target whose short-time pulse light is backscattered by the observation target and whose absorption state is adjusted;
A light intensity acquisition procedure for acquiring the intensity of light received by the light receiving procedure at a predetermined time after the time of irradiation of the short-time pulse light in the irradiation procedure;
An optical path length acquisition procedure for acquiring an optical path length of each of the plurality of layers at the predetermined time of the model of the optical path length distribution from the optical path length distribution storage unit;
A light intensity model acquisition procedure for acquiring a light intensity model at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage unit;
The light intensity acquired in the light intensity acquisition procedure, the optical path length of each of the plurality of layers acquired in the optical path length acquisition procedure, and the light intensity model acquired in the light intensity model acquisition procedure. Based on the absorption coefficient calculation procedure for calculating the absorption coefficient of the arbitrary layer,
A concentration calculation procedure for calculating the concentration of the target component in the arbitrary layer based on the absorption coefficient calculated in the absorption coefficient calculation procedure;
A program that executes

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