JP5674093B2 - Concentration determination apparatus, concentration determination method, and program - Google Patents

Description

  The present invention relates to a concentration quantification apparatus, a concentration quantification method, and a program for non-invasively quantifying the concentration of a target component in an arbitrary layer among observation targets configured by a plurality of light scattering medium layers.

In recent years, Japan is in the age of satiety, and the number of diabetic patients continues to increase every year. For this reason, 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. Among them, the blood glucose level measurement can evaluate the reaction of glucose metabolism at the very early stage of diabetes, and enables early treatment based on early diagnosis of diabetes.

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.

In view of this, an apparatus that non-invasively measures blood glucose levels has been proposed by applying a spectroscopic analyzer that uses the principle of molecular absorption to a blood glucose level measuring apparatus (see, for example, Patent Document 1).
This device irradiates the skin with near-infrared continuous light and calculates the glucose concentration from the amount of light absorption. Specifically, a calibration curve showing the relationship between the glucose concentration, the wavelength of the near infrared light to be irradiated and the amount of light absorbed is prepared in advance, and the skin is irradiated with continuous light of the near infrared, By scanning a certain wavelength region using a monochromator or the like, the amount of light absorbed for each wavelength in the wavelength region is obtained, and the amount of light absorbed at each wavelength is compared with a calibration curve to obtain blood. The glucose concentration in the blood, that is, the blood glucose level is calculated.

In general, when near-infrared spectroscopic analysis of an aqueous solution or a sample having a high water content is performed, the spectrum has a large fluctuation such as a shift of the spectrum accompanying a temperature change, like the spectrum of water. Therefore, when quantitative analysis is performed using near-infrared spectroscopy, the influence of the temperature of the aqueous solution or sample cannot be ignored.
Therefore, when measuring the glucose concentration in the tissue near the living body surface using light absorption in the near infrared region, the measurement surface of the probe tip of the optical fiber bundle for near infrared light transmission and reception and the living body There has also been proposed an apparatus for making the temperature of the contact portion with the tissue near the surface constant by using a heater and a surface temperature detecting means (see Patent Document 2).

Japanese Patent No. 3931638 JP 2001-299727 A

However, in the conventional method of measuring glucose concentration in blood or tissue near the surface of a living body from the amount of absorption of near-infrared light, the temperature change of the absorption coefficient with respect to the near-infrared light of water contained in the blood or living body There is a problem that the rate is high and it is difficult to accurately measure the glucose concentration in blood or in the living body.
For example, if the temperature of the contact portion between the measurement surface of the probe tip of the optical fiber bundle for near-infrared light transmission and reception and the tissue in the vicinity of the surface of the living body is made constant using a heater and surface temperature detection means, The temperature of the contact part is constant, but if the temperature of the living body itself changes, the temperature of the tissue near the surface of the living body also changes and the absorption coefficient for near infrared light changes. It is difficult to accurately measure the glucose concentration.

  The present invention has been made in order to solve the above-described problem, and even when the temperature of the observation target itself, which is an object to be measured such as skin, changes, the near-infrared water contained in the observation target. Provided are a concentration quantification apparatus, a concentration quantification method, and a program capable of noninvasively measuring the concentration of a target component contained in an observation target by reducing the temperature change rate of the absorption coefficient with respect to light. For the purpose.

In order to solve the above problems, the present invention employs the following concentration determination apparatus, concentration determination method, and program.
That is, the concentration quantification device of the present invention is a concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets configured by a plurality of light scattering medium layers, Irradiation means for irradiating light of a specific wavelength with a small temperature change of the water absorption coefficient in an arbitrary layer, and from the arbitrary layer from a plurality of types of backscattered light emitted from the observation object by irradiating the light Light scattering medium layer selection means for selecting emitted backscattered light, light receiving means for receiving backscattered light emitted from the arbitrary layer, and light intensity acquisition for obtaining the intensity of light received by the light receiving means A light absorption coefficient calculating means for calculating a light absorption coefficient of the arbitrary layer based on the light intensity acquired by the light intensity acquiring means, and a light absorption coefficient calculated by the light absorption coefficient calculating means. ,Previous And concentration calculation means for calculating the concentration of the target component in any layer, it is characterized in that it comprises a.

In the concentration determination apparatus of the present invention, the irradiation object is irradiated with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer by the irradiation unit, and the light is scattered by the light scattering medium layer selection unit. The backscattered light emitted from the arbitrary layer is selected from a plurality of types of backscattered light emitted from the observation object by irradiation, and the backscattered light emitted from the arbitrary layer is received by the light receiving means. To do.
In this way, the influence of water on the backscattered light emitted from any layer can be reduced by making the light irradiated to the observation object light of a specific wavelength with a small temperature change of the water absorption coefficient. In addition, the influence of water can be reduced even in the concentration of the target component in an arbitrary observation target layer calculated based on the backscattered light. Therefore, the influence of water on the concentration of the target component can be reduced, and the concentration of the target component can be accurately measured noninvasively.

（但し、Ｉ（ｔ）は前記受光手段が時刻ｔにて受光した光強度、Ｎ（ｔ）は前記短時間パルス光の時間分解波形のモデルの時刻ｔにおける光強度、Ｌｉ（ｔ）は前記複数の光散乱媒質の各々の層における伝搬光路長分布のモデルの時刻ｔにおける第ｉ層の光路長、μｉは第ｉ層の光吸収係数である）
から算出することを特徴とする。 The concentration quantification device according to the present invention uses the light as a short-time pulse light, and further propagates the optical path length of each of the layers of the plurality of light scattering media of the short-time pulse light irradiated onto the observation target. From the optical path length distribution storage means for storing the model of distribution, the time-resolved waveform storage means for storing the model of the time-resolved waveform of the short-time pulse light irradiated to the observation object, and the optical path length distribution storage means, From the optical path length acquisition means for acquiring the optical path length of each of the layers of the light scattering medium at the predetermined time of the model of the propagation optical path length distribution, and the short-time pulse from the time-resolved waveform storage means A light intensity model acquisition means for acquiring the light intensity at the predetermined time of the model of the time-resolved waveform of light,
The light intensity acquisition means acquires the light intensity at a plurality of times t _{1 to} t _m of the arbitrary layer,
The light absorption coefficient calculating means calculates the light absorption coefficient of the arbitrary layer by the following formula (1):

(Where I (t) is the light intensity received by the light receiving means at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light, and Li (t) is the light intensity (The optical path length of the i-th layer at time t in the model of the propagation optical path length distribution in each layer of the plurality of light scattering media, and μ i is the light absorption coefficient of the i-th layer)
It is characterized by calculating from.

In the concentration determination apparatus of the present invention, 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 light absorption coefficient calculation unit calculates the light absorption coefficient of the arbitrary layer as described above. Is calculated from the equation (1).
Thus, by measuring the time-resolved backscattered light, it is possible to reduce backscattered light from a layer other than an arbitrary layer as noise, and to reduce the influence of water on the concentration of the target component. Therefore, the concentration of the target component can be measured with higher accuracy.

  In the concentration quantification device according to the present invention, the plurality of times when the light intensity acquisition unit acquires the light intensity includes a peak time of a propagation optical path length distribution of each layer of the plurality of light scattering media.

  In the concentration quantification apparatus of the present invention, the plurality of times when the light intensity acquisition means acquires the light intensity includes the peak time of the propagation optical path length distribution of each layer of the plurality of light scattering media, so Any layer can be efficiently selected from these layers. Therefore, the concentration of the target component in any layer can be measured with higher accuracy.

（但し、Ｉ（ｔ）は前記受光手段が時刻ｔにて受光した光強度、Ｎ（ｔ）は前記短時間パルス光の時間分解波形のモデルの時刻ｔにおける光強度、Ｌｉ（ｔ）は前記複数の光散乱媒質の層各々の層における伝搬光路長分布のモデルの時刻ｔにおける第ｉ層の光路長、ｎは前記観測対象となる層の数、μｉは第ｉ層の光吸収係数である）
から算出することを特徴とする。 The concentration quantification device according to the present invention uses the light as a short-time pulse light, and further propagates the optical path length of each of the layers of the plurality of light scattering media of the short-time pulse light irradiated onto the observation target. From the optical path length distribution storage means for storing the model of distribution, the time-resolved waveform storage means for storing the model of the time-resolved waveform of the short-time pulse light irradiated to the observation object, and the optical path length distribution storage means, From the optical path length acquisition means for acquiring the optical path length of each of the layers of the light scattering medium at the predetermined time of the model of the propagation optical path length distribution, and the short-time pulse from the time-resolved waveform storage means A light intensity model acquisition means for acquiring the light intensity at the predetermined time of the model of the time-resolved waveform of light,
The light intensity acquisition means acquires light intensity between a predetermined time and at least a predetermined time τ,
The light absorption coefficient calculating means calculates the light absorption coefficient of the arbitrary layer by the following equation (2):

(Where I (t) is the light intensity received by the light receiving means at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light, and Li (t) is the light intensity The optical path length of the i-th layer at time t in the model of the propagation optical path length distribution in each layer of the plurality of light scattering media, n is the number of layers to be observed, and μi is the light absorption coefficient of the i-th layer. )
It is characterized by calculating from.

In the concentration determination apparatus of the present invention, the light intensity acquisition means acquires a temporal change in light intensity between a predetermined time and at least a predetermined time τ, and the light absorption coefficient calculation means calculates the light absorption coefficient of an arbitrary layer. , Calculated from the above equation (2).
Thus, by measuring the time-resolved backscattered light, it is possible to reduce backscattered light from a layer other than an arbitrary layer as noise, and to reduce the influence of water on the concentration of the target component. Therefore, the concentration of the target component can be measured with higher accuracy.

（但し、μａは前記任意の層である第ａ層における光吸収係数、ｇｊは前記観測対象を構成する第ｊ成分のモル濃度、εｊは第ｊ成分の光吸収係数、ｐは前記観測対象を構成する主成分の個数、ｑは前記特定波長の種類数である）
から算出することを特徴とする。 In the concentration quantification apparatus of the present invention, the concentration calculation means calculates the concentration of the target component in the arbitrary layer by the following equation (3):

(Where μa is the light absorption coefficient in the a-th layer which is the arbitrary layer, gj is the molar concentration of the j-th component constituting the observation object, εj is the light absorption coefficient of the j-th component, and p is the observation object. (The number of constituent main components, q is the number of types of the specific wavelength)
It is characterized by calculating from.

In the concentration determination apparatus of the present invention, the concentration calculation means calculates the concentration of the target component in an arbitrary layer from the above equation (3).
Thus, the influence of water on the concentration of the target component can be reduced by calculating the concentration of the target component in an arbitrary layer using the backscattered light that is time-resolved and measured. Therefore, the concentration of the target component can be measured with higher accuracy.

The concentration quantification method of the present invention is a concentration quantification method for quantifying the concentration of a target component in an arbitrary layer among observation targets configured by a plurality of light scattering medium layers,
Irradiation means irradiates the observation target with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer, and then the light scattering medium layer selection means irradiates the light with the observation. The backscattered light emitted from the arbitrary layer is selected from a plurality of types of backscattered light emitted from the object, and then the backscattered light emitted from the arbitrary layer is received by the light receiving means, and then The light intensity acquisition means acquires the intensity of the light received by the light receiving means, and then the light absorption coefficient calculation means calculates the light absorption coefficient of the arbitrary layer based on the light intensity acquired by the light intensity acquisition means. Then, the concentration calculation means calculates the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculation means.

In the concentration quantification method of the present invention, the observation object is irradiated with light having a specific wavelength at which the temperature change of the water absorption coefficient in the arbitrary layer is small, and then the light scattering medium layer selection means is used to irradiate the observation target. Back-scattered light emitted from the arbitrary layer is selected from a plurality of types of back-scattered light emitted from the observation target by irradiating light, and then the back-radiated from the arbitrary layer by the light receiving means Receives scattered light.
In this way, by irradiating the observation target with light having a specific wavelength with a small temperature change in the absorption coefficient of water in an arbitrary layer, the influence of water on the backscattered light emitted from the arbitrary layer can be reduced. The influence of water can be reduced even in the concentration of the target component in an arbitrary observation target layer calculated based on the backscattered light. Therefore, the influence of water on the concentration of the target component can be reduced, and the concentration of the target component can be measured noninvasively with high accuracy and efficiency.

  The program of the present invention includes a computer for a concentration quantification apparatus that quantifies the concentration of a target component in an arbitrary layer among observation targets configured by a plurality of light scattering medium layers, Irradiation procedure for irradiating light of a specific wavelength with a small temperature change in water absorption coefficient, backscattering radiated from the arbitrary layer from multiple types of backscattered light radiated from the observation object by irradiating the light Light scattering medium layer selection procedure for selecting light, light reception procedure for receiving backscattered light emitted from the arbitrary layer, light intensity acquisition procedure for acquiring the intensity of light received by the light receiving means, and the light intensity acquisition means The light absorption coefficient calculation procedure for calculating the light absorption coefficient of the arbitrary layer based on the obtained light intensity, and the light absorption coefficient calculated by the light absorption coefficient calculation means in the arbitrary layer. Density calculation step of calculating the concentration of the target component that, characterized in that for the execution.

In the program of the present invention, the computer of the concentration quantification apparatus irradiates the observation object with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer, Light scattering medium layer selection procedure for selecting backscattered light emitted from the arbitrary layer from a plurality of types of backscattered light emitted from the observation target, and a light receiving procedure for receiving the backscattered light emitted from the arbitrary layer Are sequentially executed.
In this way, by performing an irradiation procedure that irradiates light of a specific wavelength with a small temperature change in the absorption coefficient of water in an arbitrary layer, the influence of water on backscattered light emitted from the arbitrary layer is reduced. The influence of water can be reduced even in the concentration of the target component in an arbitrary observation target layer calculated based on the backscattered light. Therefore, the influence of water on the concentration of the target component can be reduced, and the concentration of the target component can be measured noninvasively with high accuracy and efficiency.

It is a schematic block diagram which shows the structure of the blood glucose level measuring apparatus of the 1st Embodiment of this invention. It is a schematic diagram which shows the cross-sectional structure of skin. It is a figure which shows the propagation optical path length distribution of each layer which the simulation part computed. It is a figure which shows the time-resolved waveform which the simulation part computed. It is a figure which shows the light absorption wavelength characteristic by water. It is a figure which shows the absorption spectrum of the main component of skin. It is a figure which shows the relationship between the wavelength of the light irradiated to each of the subcutaneous tissue of skin, a dermis layer, and an epidermis layer, and an absorption coefficient. It is a figure which shows the temperature dependence of the absorbance spectrum of water. It is a figure which shows the temperature dependence of the difference of the absorption spectrum of water. It is a figure which shows an example of the absorbance spectrum of glucose aqueous solution. It is a flowchart which shows the procedure which measures the blood glucose level of the 1st Embodiment of this invention. It is a schematic block diagram which shows the structure of the blood glucose level measuring apparatus of the 2nd Embodiment of this invention. It is a flowchart which shows the procedure which measures the blood glucose level of the 2nd Embodiment of this invention.

An embodiment for carrying out a concentration determination apparatus, a concentration determination method, and a program according to 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, glucose as a target component, and short-time pulsed light of a specific wavelength as light of a specific wavelength will be described as examples. .

[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.
This blood glucose level measuring device 1 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. Yes, a simulation unit 2, an optical path length distribution storage unit (optical path length distribution storage unit) 3, a time-resolved waveform storage unit (time-resolved waveform storage unit) 4, an irradiation unit (irradiation unit) 5, and a light guide unit 6 A light scattering medium layer selection unit (light scattering medium layer selection unit) 7, a light receiving unit (light receiving unit) 8, a light intensity acquisition unit (light intensity acquisition unit) 9, and an optical path length acquisition unit (optical path length acquisition unit). ) 10, a non-absorption light intensity acquisition unit (light intensity model acquisition unit) 11, a light absorption coefficient calculation unit (light absorption coefficient calculation unit) 12, and a concentration calculation unit (concentration calculation unit) 13.

The simulation unit 2 performs a simulation of irradiating light to a skin model having a light absorption coefficient of zero.
The optical path length distribution storage unit 3 stores a model of a propagation optical path length distribution in each layer constituting the skin of short-time pulse light irradiated to the skin. Here, the propagation optical path length distribution of the skin model having zero light absorption coefficient is stored.
The time-resolved waveform storage unit 4 stores a model of a time-resolved waveform of short-time pulse light that is applied to the skin. Here, the time-resolved waveform of the skin model having zero light absorption coefficient is stored.
The irradiation unit 5 irradiates the skin with short-time pulsed light having a specific wavelength λk (λ ₁ , λ ₂ ...) With a small temperature change of the water absorption coefficient in the dermis layer constituting the skin. Here, the short-time pulsed light means pulsed light having a pulse width of about 100 psec or less. Note that pulse light having a pulse width in the range of 0.1 psec to several psec may be used as the short-time pulse light.

The light guide unit 6 collects a plurality of types of backscattered light emitted from the skin by irradiating the skin with the short-time pulsed light having the specific wavelength λk, and guides the light to the light scattering medium layer selecting unit 7. To do.
The light scattering medium layer selection unit 7 converts the backscattered light radiated by the dermis layer from the multiple types of backscattered light emitted from the skin condensed and guided by the light guide unit 6, as the distance between the input and output. The selection is made according to the relationship with the reach in the depth direction in the living body.
The light receiving unit 8 receives light obtained by backscattering the short-time pulsed light by the skin.

The light intensity acquisition unit 9 acquires the light reception intensities at different times of the backscattered light emitted from the dermis layer received by the light receiving unit 8.
Here, it is preferable that the plurality of times include the peak time of the propagation optical path length distribution of each layer constituting the skin (observation target).
As described above, by including the peak time of the propagation optical path length distribution of each layer, an arbitrary layer, for example, the dermis layer can be efficiently selected from a plurality of skin layers.

The optical path length acquisition unit 10 acquires from the optical path length distribution storage unit 3 the optical path length of each layer of the skin at a predetermined time of the model of the propagation optical path length distribution. Here, the optical path length at a certain time is acquired from the optical path length distribution storage unit 3.
The non-absorption light intensity acquisition unit 11 acquires the light intensity at a predetermined time of the model of the time-resolved waveform of the short-time pulsed light from the time-resolved waveform storage unit 4. Here, the light intensity at a certain time is acquired from the time-resolved waveform storage unit 4.
The light absorption coefficient calculation unit 12 calculates the light absorption coefficient in the dermis layer of the skin irradiated with the short-time pulse light with the specific wavelength λk.

（但し、Ｉ（ｔ）は受光部８が時刻ｔにて受光した光強度、Ｎ（ｔ）は特定波長λｋの短時間パルス光の時間分解波形のモデルの時刻ｔにおける光強度、Ｌｉ（ｔ）は皮膚の各々の層における伝搬光路長分布のモデルの時刻ｔにおける第ｉ層の光路長、μｉは第ｉ層の光吸収係数である）
から算出する。
ここで、第１層は表皮層、第２層は真皮層、第３層は皮下組織を示し、μ_１は表皮層の光吸収係数、μ_２は真皮層の光吸収係数、μ_３は皮下組織の光吸収係数を示す。 In the light absorption coefficient calculation unit 12, the light absorption coefficient of an arbitrary layer in the skin is expressed by the following equation (4).

(Where I (t) is the light intensity received by the light receiving unit 8 at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light of the specific wavelength λk, and Li (t ) Is the optical path length of the i-th layer at time t of the model of the propagation optical path length distribution in each layer of the skin, and μ i is the light absorption coefficient of the i-th layer)
Calculate from
Here, the first layer is the epidermis layer, the second layer is the dermis layer, the third layer is the subcutaneous tissue, μ ₁ is the light absorption coefficient of the epidermis layer, μ ₂ is the light absorption coefficient of the dermis layer, and μ ₃ is the subcutaneous Shows the light absorption coefficient of tissue.

（但し、μａは皮膚の任意の層である第ａ層における光吸収係数、ｇｊは皮膚を構成する第ｊ成分のモル濃度、εｊは第ｊ成分の光吸収係数、ｐは皮膚を構成する主成分の個数、ｑは特定波長λｋの種類数である）
から算出する。
ここで、第１層は表皮層、第２層は真皮層、第３層は皮下組織を示し、μ_１は表皮層の光吸収係数、μ_２は真皮層の光吸収係数、μ_３は皮下組織の光吸収係数を示す。 The concentration calculation unit 13 calculates the concentration of glucose contained in the dermis layer from the light absorption coefficient in the dermis layer.
In the concentration calculation unit 13, the glucose concentration in an arbitrary layer of the skin is expressed by the following equation (5).

(Where μa is the light absorption coefficient in the a layer, which is an arbitrary layer of the skin, gj is the molar concentration of the jth component constituting the skin, εj is the light absorption coefficient of the jth component, and p is the main component constituting the skin. The number of components, q is the number of types of specific wavelength λk)
Calculate from
Here, the first layer is the epidermis layer, the second layer is the dermis layer, the third layer is the subcutaneous tissue, μ ₁ is the light absorption coefficient of the epidermis layer, μ ₂ is the light absorption coefficient of the dermis layer, and μ ₃ is the subcutaneous Shows the light absorption coefficient of tissue.

In this blood sugar level measuring apparatus 1, the irradiation unit 5 has a specific wavelength λk, for example, λ ₁ = 1445 nm, λ ₂ =, where the temperature change of the water absorption coefficient in the dermis layer 23 constituting the skin 21 is small. Irradiation with short-time pulsed light having a wavelength of 1782 nm is performed. The light guide 6 collects multiple types of backscattered light emitted from the skin 21. The light scattering medium layer selection unit 7 converts the backscattered light radiated by the dermis layer 23 from the multiple types of backscattered light radiated from the skin 21, and the distance between the entrance and exit and the reach in the depth direction in the living body. Select by relationship. The light receiving unit 8 receives signal light including more backscattered light emitted from the dermis layer 23.

Furthermore, the light intensity acquisition unit 9 acquires the light intensity of the backscattered light emitted from the dermis layer 23 received by the light receiving unit 8 at time t.
On the other hand, the optical path length acquisition unit 10 acquires the optical path length of each layer of the skin at the time t of the propagation optical path length distribution in the skin model from the optical path length distribution storage unit 3, and the non-absorbing light intensity acquisition unit 11 has a time-resolved waveform. 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 storage unit 4.

Next, the light absorption coefficient calculation unit 12 includes the light intensity acquired by the light intensity acquisition unit 9, the optical path length of each layer of the skin acquired by the optical path length acquisition unit 10, and the light intensity acquired by the non-absorption light intensity acquisition unit 11. Based on the above, the light absorption coefficient of the dermis layer of the skin is calculated. Next, the concentration calculator 13 calculates the concentration of glucose contained in the dermis layer 23 based on the above equation (5) based on the light absorption coefficient calculated by the light absorption coefficient calculator 12.
Thereby, the influence of noise by layers other than the dermis layer can be reduced, and the concentration of glucose contained in the dermis layer can be calculated.

  As described above, the influence of water in the backscattered light radiated from the dermis layer 23 can be reduced, and the concentration of glucose contained in the dermis layer 23 calculated based on this backscattered light is also affected by water. Can be small. Therefore, the influence of water on the glucose concentration can be reduced, and the glucose concentration contained in the dermis layer 23 can be accurately measured noninvasively.

Next, the operation of the blood sugar level measuring apparatus 1 will be described.
The blood glucose level measuring apparatus 1 needs to calculate the propagation optical path length distribution and the time-resolved waveform in each layer of the skin model before measuring the blood glucose level.
FIG. 2 is a schematic diagram showing a cross-section of human skin tissue. The skin 21 includes approximately 20% of water and the rest of the skin layer 22 is approximately 0.3 mm thick and is below the skin layer 22. A dermis layer (arbitrary layer) 23 having a thickness of about 1.2 mm containing about 60% water and containing protein, lipid and glucose, and formed under the dermis layer 23, and generally containing 90% or more of lipid, The remaining part is composed of water and a subcutaneous tissue 24 having a thickness of about 3.0 mm.

Here, a method of calculating the propagation optical path length distribution and time-resolved waveform of the skin model will be described.
First, the simulation unit 2 generates a skin model. The skin model is generated by determining the light scattering coefficient, light absorption coefficient, and thickness of each layer of the skin. Here, since the scattering coefficient and thickness of each layer of the skin have little difference between individuals, it is preferable to determine by taking a sample in advance.
The light 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 2 generates a skin model, the simulation unit 2 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 5 and the position of the light receiving unit 8. The simulation is preferably performed using the Monte Carlo method. The simulation by the Monte Carlo method is performed as follows, for example.

ただし、μｓは、皮膚モデルの第ｓ層（表皮層、真皮層、皮下組織層の何れか）の散乱係数を示す。 First, the simulation unit 2 performs calculation for irradiating the skin model with a photon (light beam) as a model of light to be irradiated. Photons irradiated to the skin model move in the skin model. At this time, the photon determines the distance L and the direction θ to the next advancing point by the random number R. The simulation unit 2 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.

ただし、ｇは、散乱角度の余弦（ｃｏｓ）の平均である非等方性パラメータを示し、皮膚の非等方性パラメータは、略０．９である。 In addition, the simulation unit 2 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 the cosine (cos) of a scattering angle, and the anisotropic parameter of skin is about 0.9.

The simulation unit 2 can calculate the movement path of photons from the irradiation unit 5 to the light receiving unit 8 by repeating the calculations of the above formulas (6) and (7) every unit time. The simulation unit 2 calculates the movement distance for a plurality of photons. For example, the simulation unit 2 calculates the movement distance for 10 ⁸ photons.

FIG. 3 is a diagram illustrating the propagation optical path length distribution of each layer calculated by the simulation unit.
In FIG. 3, the horizontal axis is the elapsed time from photon irradiation, and the vertical axis is a logarithmic display of the optical path length.
The simulation unit 2 classifies each movement path of the photons that have reached the light receiving unit 8 for each layer through which the movement path passes. And the simulation part 2 calculates the propagation | transmission optical path length distribution of each layer of skin as shown in FIG. 3 by calculating the average length of the movement path | route of the photon which arrived for every unit time for every classified layer.

FIG. 4 is a diagram illustrating a time-resolved waveform calculated by the simulation unit.
In FIG. 4, 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 8.
The simulation unit 2 calculates a time-resolved waveform of the skin model as shown in FIG. 4 by calculating the number of photons that reach the light receiving unit 8 per unit time.
Through the processing described above, the simulation unit 2 calculates the propagation optical path length distribution and time-resolved waveform of the skin model for a plurality of wavelengths. At this time, the simulation unit 2 may calculate a propagation 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. 5 is a diagram showing the light absorption wavelength characteristics of water (by Kubo U. City, “Introduction to Medical Lasers”, 1st edition, Ohmsha, published on June 25, 1985, page 70, ISBN4-274). -03065-2).
In FIG. 5, the horizontal axis represents the wavelength of light (μm), the vertical axis represents the penetration depth (cm) of the light into the skin, and the light intensity at the time of incidence when entering the water. Shows the penetration depth that advances until it decreases to 1/10 for light of each wavelength in the infrared region.
For example, it can be seen that light having a wavelength band near 3.0 μm has a penetration depth as shallow as about 2 × 10 ⁻³ cm and is easily absorbed by water.

FIG. 6 is a graph showing the absorption spectrum of the main component of the skin. In FIG. 6, the horizontal axis represents the wavelength of light to be irradiated, and the vertical axis represents the absorption coefficient.
According to FIG. 6, it can be seen 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 2 may calculate the propagation 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 2 calculates the propagation optical path length distribution and the time-resolved waveform of the skin model for a plurality of wavelengths, the simulation unit 2 stores the information on the propagation optical path length distribution in the optical path length distribution storage unit 3 and the time-resolved waveform information as the time-resolved waveform. Store in the storage unit 4.

FIG. 7 is a diagram showing the relationship between the wavelength of light applied to each of the epidermis layer 22, the dermis layer 23, and the subcutaneous tissue 24 of the skin 21, and the absorption coefficient, where A represents the absorption coefficient of the epidermis layer 22. , B indicate the absorption coefficient of the dermal layer 23, and C indicates the absorption coefficient of the subcutaneous tissue 24, respectively.
According to this figure, the absorption spectrum of the dermis layer 23 has a maximum value near the wavelength of 1450 nm, and its absorption coefficient value is about 60% of the absorption coefficient of water, so that 60% of the absorption of the dermis layer 23 is It is thought to be due to moisture. Also in the absorption spectrum of the skin layer 22, there is a maximum value of about 1/3 of the dermal layer 23 in the vicinity of the wavelength of 1450 nm, and the absorption coefficient value is about 20% of the water absorption coefficient. It is believed that 20% of the absorption of layer 22 is due to moisture. On the other hand, in the absorption spectrum of the subcutaneous tissue 24, there is only a maximum value of about 1/10 the size of the dermis layer 23 near the wavelength of 1450 nm, and the absorption coefficient value is about several percent of the absorption coefficient of water. It is considered that about several percent of the absorption of 24 is due to moisture.

  From the above, 60% of the absorption of the dermis layer 23 is considered to be due to moisture, and 20% of the absorption of the epidermis layer 22 is considered to be due to moisture. It is thought to be due to moisture. Therefore, it can be understood that in order to non-invasively measure the blood glucose level from the skin, it is only necessary to select the dermis layer 23 containing glucose as a measurement target and measure the amount of glucose contained in the dermis layer 23.

Incidentally, it is known that the absorption coefficient of water has temperature dependency.
FIG. 8 is a diagram showing the temperature dependence of the water absorbance spectrum, in which A is the water absorbance spectrum at 41 ° C. and B is the water absorbance spectrum at 21 ° C.
Here, an optical cell with a cell length of 0.5 mm is used, a temperature control unit type optical cell holder is used, and the temperature is adjusted within a range of ± 0.1 ° C. using a thermostatic circulation tank, and ultraviolet, visible and near infrared are used. Absorbance spectra of water at 41 ° C. and 21 ° C. were measured using a spectrophotometer Lambda 900S (Perkin Elmer).
According to FIG. 8, the maximum value of the absorbance spectrum of water is near the wavelength of 1450 nm at 21 ° C., and the maximum value shifts to the shorter wavelength side from 1450 nm as the temperature becomes higher than 21 ° C.

Therefore, if the difference from the standard of the absorbance spectrum of water at a temperature other than 21 ° C. is obtained on the basis of the absorbance spectrum of water at 21 ° C., and the wavelength at the point where this difference is “0” is obtained, this wavelength becomes the temperature. The wavelength is not affected by the change.
FIG. 9 is a diagram showing the temperature dependence of the difference in the absorbance spectrum of water, in which A is the difference between the water absorbance spectrum at 25 ° C. and the water absorbance spectrum at 21 ° C., and B is at 31 ° C. The difference between the absorbance spectrum of water and the absorbance spectrum of water at 21 ° C., C is the difference between the absorbance spectrum of water at 37 ° C. and the absorbance spectrum of water at 21 ° C., and D is the absorbance spectrum of water at 41 ° C. The difference from the absorbance spectrum of water at ° C. is shown respectively.

  According to FIG. 9, the maximum value of the difference in the absorbance spectrum of water at each temperature difference shifts to the shorter wavelength side as the temperature difference increases, and the minimum value of the difference increases as the temperature difference increases. Although it is shifted to the long wavelength side, it can be seen that the wavelength is constant regardless of the temperature difference at the points P and Q where the difference in the absorbance spectrum of water is “0”. In this case, the wavelength at the point P is 1445 nm, and the wavelength at the point Q is 1782 nm. Therefore, if the absorbance spectrum of the sample is measured using light having a specific wavelength λk of either 1445 nm or 1782 nm, the obtained absorbance spectrum is not affected by temperature changes.

As an example, for two types of wavelengths of 1445 nm and 1782 nm, the range of absorbance and absorption coefficient that can be regarded as stable with respect to temperature change when the blood glucose level is 100 mg / dl and the measurement accuracy is ± 5% is experimentally determined. In the wavelength of 1445 nm, they were 1.35 ± 0.0000175 and ± 0.00004 / mm, and in the wavelength of 1782 nm, they were 0.39 ± 0.0000175 and ± 0.00004 / mm. Therefore, when the wavelength range was determined from the ranges of the absorbance and the absorption coefficient, they were 1445 ± 0.025 nm and 1782 ± 0.1 nm.
As a result, it was found that the wavelength ranges that can be regarded as stable with respect to temperature changes when the blood glucose level was 100 mg / dl and the measurement accuracy was ± 5% were 1445 ± 0.025 nm and 1782 ± 0.1 nm.

  As described above, if the amount of glucose contained in the dermis layer 13 is measured using short-time pulsed light having a specific wavelength λk in which the temperature change of the water absorption coefficient in the dermis layer is small, the blood glucose level can be measured non-invasively from the skin. can do.

  FIG. 10 is a diagram showing an example of the absorbance spectrum of an aqueous glucose solution. In the figure, A is the absorbance spectrum of a high-concentration glucose aqueous solution of 9.4 g / dl measured using the reference side as distilled water (21.5 ° C.). B represents a correction value obtained by temperature correction and volume correction of the measurement value of the absorbance spectrum of the glucose aqueous solution.

In this glucose aqueous solution, since the glucose concentration was 9.4 g / dl, which is about 100 times the normal value, the volume increase at this time is about 6%.
At this concentration, the volume ratio of glucose and water is as large as 6: 100 and cannot be ignored. Thus, since the volume of water on the sample side is reduced compared to the volume of water on the reference side, the absorbance spectrum difference is greatly negative in the vicinity of 1400-1500 nm where the absorbance of water is large and in the wavelength region of 1900 nm or more. It has become. This volume reduction corresponds to a reduction of 0.057 mm for a cell length of 1 mm. Therefore, when this volume reduction and temperature correction are performed on the measured value of the absorbance spectrum of the glucose aqueous solution, the correction value shown in FIG. 10B is obtained, which approximates the absorbance spectrum of solid glucose.
In this way, by performing temperature correction and volume correction on the measured value of the absorbance spectrum of the glucose aqueous solution, a value close to the absorbance spectrum of glucose alone can be obtained.

Next, a procedure for measuring a blood sugar level using the blood sugar level measuring apparatus 1 will be described with reference to FIG.
First, the person to be measured applies the blood sugar level measuring device 1 to the skin such as the wrist, and operates the blood sugar level measuring device 1 by pressing a measurement start switch (not shown) or the like.
Here, the irradiation unit 5 irradiates the skin 21 with short-time pulsed light having a specific wavelength λk in which the temperature change of the water absorption coefficient in the dermis layer 23 constituting the skin 21 is small (step S1).
As this specific wavelength λk, for example, it is preferable to use one of 1445 nm and 1782 nm obtained in FIG. 9 or both wavelengths.

Next, the light guide unit 6 collects a plurality of types of backscattered light emitted from the skin 21, that is, backscattered light emitted from each of the subcutaneous tissue 22, the dermis layer 23, and the epidermis layer 24, and a light scattering medium layer. The light is guided to the selection unit 7.
In the light scattering medium layer selection unit 7, the dermis layer 23 emits the backscattered light emitted from each of the subcutaneous tissue 22, the dermis layer 23, and the epidermis layer 24 collected and guided by the light guide unit 6. A signal light containing more backscattered light is selected (step S2).

Next, the light receiving unit 8 receives backscattered light per unit time emitted from the dermis layer 23 (step S3). At this time, the light receiving unit 8 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 the internal memory.

When the light intensity acquisition unit 9 notifies the light intensity acquisition unit 9 that the light reception has been completed, the light intensity acquisition unit 9 acquires the light reception intensity at different times of the backscattered light emitted from the dermis layer 23 (step S4). ). That is, the light intensity of the backscattered light at each of the plurality of times t _{1 to} t _m is acquired.
Here, it is preferable that the times t ₁ to t _m at which the light intensity acquisition unit 9 acquires the light intensity include the time at which the peak of the backscattered light emitted from the dermis layer 23 is obtained. That is, it is preferable that the time when the light path length of the dermis layer 23 is maximized is added to the time when the irradiation unit 5 emits the short-time pulsed light with the specific wavelength λ1.

（但し、Ｉ（ｔ）は受光部５が時刻ｔにて受光した光強度、Ｎ（ｔ）は特定波長λｋの短時間パルス光の時間分解波形のモデルの時刻ｔにおける光強度、Ｌｉ（ｔ）は皮膚の各々の層における伝搬光路長分布のモデルの時刻ｔにおける第ｉ層の光路長、μｉは第ｉ層の光吸収係数である）
から算出する（ステップＳ５）。
ここでは、第１層は表皮層、第２層は真皮層、第３層は皮下組織を示し、μ_１は表皮層の光吸収係数、μ_２は真皮層の光吸収係数、μ_３は皮下組織の光吸収係数を示す。 Next, in the light absorption coefficient calculation unit 12, the received light intensity at different times of the backscattered light emitted from the dermis layer 23 acquired by the light intensity acquisition unit 9, that is, backscattering at each of a plurality of times t _{1 to} t _m. Based on the light intensity of light, the light absorption coefficient of the dermis layer 23 is expressed by the following equation (8).

(Where I (t) is the light intensity received by the light receiving unit 5 at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light of the specific wavelength λk, and Li (t ) Is the optical path length of the i-th layer at time t of the model of the propagation optical path length distribution in each layer of the skin, and μ i is the light absorption coefficient of the i-th layer)
(Step S5).
Here, the first layer is the epidermis layer, the second layer is the dermis layer, the third layer is the subcutaneous tissue, μ ₁ is the light absorption coefficient of the epidermis layer, μ ₂ is the light absorption coefficient of the dermis layer, and μ ₃ is the subcutaneous Shows the light absorption coefficient of tissue.

  Next, it is determined whether or not the light absorption coefficient is calculated for the same number of specific wavelengths λk as the number of types of specific wavelengths λk. If calculated, the process proceeds to the next procedure, and if not calculated, The procedure after the irradiation with the short-time pulse light with the specific wavelength λk (step S1) is performed again (step S6).

Here, if the light absorption coefficient is calculated for the same number of specific wavelengths λk as the number of types of the specific wavelength λk, the concentration calculation unit 13 calculates the light absorption coefficient of the dermis layer 23 calculated by the light absorption coefficient calculation unit 12. Based on μ, the concentration of glucose contained in the dermis layer 23 is calculated.
Here, for example, a case where the concentration of glucose is calculated from the relationship between the light absorption coefficient of the main component at a single wavelength and the light absorption coefficient of each layer will be described.
Equation (9) below shows that the light absorption coefficient of the skin is the sum of the product of the function and the coefficient relating to the wavelength of each of water, glucose, protein, lipid and other components.

Equation (10) shows the light absorption coefficient of each layer of the skin epidermis, dermis, and subcutaneous tissue from the light absorption coefficient of the skin shown in Equation (9), and the wavelength of water, glucose, protein, lipid and other components. This is the sum of the product of the light absorption coefficient and the concentration.

Formula (11) is a formula representing the above formula (10) as a matrix, and in formula (11), “C” represents water, glucose, protein for each layer of the skin epidermis, dermis, and subcutaneous tissue, It is a coefficient matrix which shows the density | concentration of each of a lipid and another component.

By transforming Equation (11), Equation (12), which is a simultaneous linear equation for solving “C”, can be derived.

Expression (13) is an expression in which Expression (12) is expressed as a matrix.

Here, with respect to the light absorption coefficient of the dermis (L2), a linear simultaneous equation represented by Expression (14) is established for the relationship between the skin principal component absorption coefficient and its concentration at a plurality of wavelengths (λ).

This equation (14) can be transformed to the equation (15).

このように、真皮（Ｌ２）に係わる係数行列「Ｃ」は、式（１６）から算出することができる。 By transforming Equation (15), Equation (16) that is a simultaneous linear equation for solving “C” can be derived.
In equation (16), ε _W is the light absorption coefficient of water, ε _G is the light absorption coefficient of glucose, ε _P is the light absorption coefficient of the protein, ε _L is the light absorption coefficient of the lipid, and μ _L1 is the light absorption coefficient of the epidermis. , mu _L2 light absorption coefficient of the dermis, the mu _L3 is a light absorption coefficient of the subcutaneous tissue. The light absorption coefficient of the skin main component and the skin layer may be further added.

Thus, the coefficient matrix “C” related to the dermis (L2) can be calculated from the equation (16).

（但し、μａは皮膚の任意の層である第ａ層における光吸収係数、ｇｊは皮膚を構成する第ｊ成分のモル濃度、εｊは第ｊ成分の光吸収係数、ｐは皮膚を構成する主成分の個数、ｑは短時間パルス光の種類数である）
から算出する（ステップＳ７）。 Furthermore, here, the explanation is based on the difference at a plurality of wavelengths.
Here, the concentration of glucose contained in the dermis layer 23 is expressed by the following equation (17).

(Where μa is the light absorption coefficient in the a layer, which is an arbitrary layer of the skin, gj is the molar concentration of the jth component constituting the skin, εj is the light absorption coefficient of the jth component, and p is the main component constituting the skin. The number of components, q is the number of types of short-time pulsed light)
(Step S7).

The blood glucose level measuring apparatus 1 described above has a built-in computer system, 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 above-described processing operation can be performed by the computer reading and executing this program.
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.
Alternatively, the computer program may be distributed to the computer via a communication line, and the computer that has received the distribution may execute the program.

The program may be for realizing a part of the above steps.
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.

  As described above, according to the present embodiment, the short-time pulse light applied to the skin is emitted from the dermis layer by making the short-time pulse light having a specific wavelength with a small temperature change in the water absorption coefficient. The influence of water in the backscattered light can be reduced, and the influence of water can also be reduced in the glucose concentration in the dermis layer of the skin calculated based on the backscattered light. Therefore, the influence of water on the glucose concentration can be reduced, and the glucose concentration contained in the dermis layer can be accurately measured noninvasively.

[Second Embodiment]
FIG. 12 is a schematic block diagram showing the configuration of the blood sugar level measuring device according to the second embodiment of the present invention, and the blood sugar level measuring device 31 of the present embodiment is different from the blood sugar level measuring device 1 of the first embodiment. The point is that the light intensity acquisition unit 9 and the light absorption coefficient calculation unit 12 are changed to a light intensity acquisition unit (light intensity acquisition unit) 32 and a light absorption coefficient calculation unit (light absorption coefficient calculation unit) 33 having functions different from these. It is a changed point.

The light intensity acquisition unit 32 acquires a temporal change in light intensity between a predetermined time and at least a predetermined time τ of backscattered light emitted from the dermis layer received by the light receiving unit 8.
The light absorption coefficient calculation unit 33 calculates the light absorption coefficient in the dermis layer of the skin irradiated with the short-time pulse light with the specific wavelength λk.

（但し、Ｉ（ｔ）は受光部５が時刻ｔにて受光した光強度、Ｎ（ｔ）は特定波長λｋの短時間パルス光の時間分解波形のモデルの時刻ｔにおける光強度、Ｌｉ（ｔ）は皮膚の各々の層における伝搬光路長分布のモデルの時刻ｔにおける第ｉ層の光路長、ｎは皮膚の観測対象となる層の数、μｉは第ｉ層の光吸収係数である）
から算出する。
ここで、第１層は表皮層、第２層は真皮層、第３層は皮下組織を示し、μ_１は表皮層の光吸収係数、μ_２は真皮層の光吸収係数、μ_３は皮下組織の光吸収係数を示す。 In this light absorption coefficient calculation unit 33, the light absorption coefficient of an arbitrary layer in the skin is expressed by the following equation (18).

(Where I (t) is the light intensity received by the light receiving unit 5 at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light of the specific wavelength λk, and Li (t ) Is the optical path length of the i-th layer at time t in the model of the propagation optical path length distribution in each layer of the skin, n is the number of layers to be observed on the skin, and μ i is the light absorption coefficient of the i-th layer)
Calculate from
Here, the first layer is the epidermis layer, the second layer is the dermis layer, the third layer is the subcutaneous tissue, μ ₁ is the light absorption coefficient of the epidermis layer, μ ₂ is the light absorption coefficient of the dermis layer, and μ ₃ is the subcutaneous Shows the light absorption coefficient of tissue.

Next, a procedure for measuring a blood glucose level using the blood glucose level measuring device 31 will be described with reference to FIG.
In this procedure, the light scattering medium layer selection unit 7 selects the backscattered light emitted from the dermis layer 23 from the backscattered light emitted from the subcutaneous tissue 22, the dermis layer 23, and the epidermis layer 24 (step S2). The procedure up to and including the procedure shown in FIG. 11 is omitted.

After selecting the backscattered light, the light receiving unit 8 receives the backscattered light for a predetermined time τ emitted from the dermis layer 23 (step S11). At this time, the light receiving unit 8 records the temporal change in the received light intensity at least during a predetermined time τ from the start of irradiation in the internal memory.
Next, when the light intensity acquisition unit 32 notifies the light intensity acquisition unit 32 that the light reception has been completed, the light intensity acquisition unit 32 at least at a predetermined time τ from the start of irradiation of the backscattered light emitted from the dermis layer 23. A change in the received light intensity over time is acquired (step S12).

（但し、Ｉ（ｔ）は受光部５が時刻ｔにて受光した光強度、Ｎ（ｔ）は特定波長λｋの短時間パルス光の時間分解波形のモデルの時刻ｔにおける光強度、Ｌｉ（ｔ）は皮膚の各々の層における伝搬光路長分布のモデルの時刻ｔにおける第ｉ層の光路長、ｎは皮膚の観測対象となる層の数、μｉは第ｉ層の光吸収係数である）
から算出する（ステップＳ１３）。 Next, in the light absorption coefficient calculation unit 33, based on the temporal change in the received light intensity at least during a predetermined time τ from the start of irradiation of the backscattered light emitted from the dermis layer 23 acquired by the light intensity acquisition unit 32, The light absorption coefficient of the dermis layer 23 is expressed by the following equation (19).

(Where I (t) is the light intensity received by the light receiving unit 5 at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light of the specific wavelength λk, and Li (t ) Is the optical path length of the i-th layer at time t in the model of the propagation optical path length distribution in each layer of the skin, n is the number of layers to be observed on the skin, and μ i is the light absorption coefficient of the i-th layer)
(Step S13).

  Next, it is determined whether or not the light absorption coefficient is calculated for the same number of specific wavelengths λk as the number of types of specific wavelengths λk. If calculated, the process proceeds to the next procedure, and if not calculated, The procedure after the irradiation with the short-time pulsed light with the specific wavelength λk (step S1) is performed again (step S14).

（但し、μａは皮膚の任意の層である第ａ層における光吸収係数、ｇｊは皮膚を構成する第ｊ成分のモル濃度、εｊは第ｊ成分の光吸収係数、ｐは皮膚を構成する主成分の個数、ｑは特定波長λｋの種類数である）
から算出する（ステップＳ１５）。 Here, if the light absorption coefficient is calculated for the same number of specific wavelengths λk as the number of types of the specific wavelength λk, the concentration calculation unit 13 calculates the light absorption coefficient of the dermis layer 23 calculated by the light absorption coefficient calculation unit 33. Based on μ, the concentration of glucose contained in the dermis layer 23 is expressed by the following equation (20).

(Where μa is the light absorption coefficient in the a layer, which is an arbitrary layer of the skin, gj is the molar concentration of the jth component constituting the skin, εj is the light absorption coefficient of the jth component, and p is the main component constituting the skin. The number of components, q is the number of types of specific wavelength λk)
(Step S15).

  Also in the present embodiment, as in the first embodiment, the influence of water in the backscattered light radiated from the dermis layer can be reduced, and in the dermis layer of the skin calculated based on this backscattered light. Even in the concentration of glucose, the influence of water can be reduced. Therefore, the influence of water on the glucose concentration can be reduced, and the glucose concentration contained in the dermis layer can be accurately measured noninvasively.

As described above, each embodiment of the present invention has been described with reference to the drawings. However, the specific configuration is not limited to the above-described one, and various design changes and the like can be made without departing from the scope of the present invention. Is possible.
For example, in each of the above embodiments, the blood glucose level measuring device as the concentration quantification device, the skin of a human palm as the observation target, glucose as the target component, short-time pulsed light of a specific wavelength as light of a specific wavelength, 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, and the concentration determination method is not limited to any layer to be observed formed from a plurality of light scattering medium layers. It may be used for other devices for quantifying the concentration of the target component in, and the short-time pulsed light with a specific wavelength may be replaced with continuous light with 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 and treatment of skin diseases.

DESCRIPTION OF SYMBOLS 1 ... Blood glucose level measuring apparatus (concentration determination apparatus), 3 ... Optical path length distribution storage part (optical path length distribution storage means), 4 ... Time-resolved waveform storage part (time-resolved waveform storage means), 5 ... Irradiation part (irradiation means) , 7... Light scattering medium layer selection section (light scattering medium layer selection means), 8. Light receiving section (light receiving means), 10... Optical path length acquisition section (light path length acquisition means), 11. Intensity model acquisition means), 12 ... light absorption coefficient calculation section (light absorption coefficient calculation means), 13 ... concentration calculation section (concentration calculation means), 21 ... skin (observation target), 23 ... dermis layer (arbitrary layer), 31 ... Blood glucose level measuring device (concentration determination device), 32 ... Light intensity acquisition unit (light intensity acquisition unit), 33 ... Light absorption coefficient calculation unit (light absorption coefficient calculation unit), S1 to S6, S11 to S14

Claims (8)

A concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of a plurality of light scattering medium layers,
Irradiation means for irradiating the observation target with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer;
A light scattering medium layer selection means for selecting time-resolved backscattered light emitted from the arbitrary layer from a plurality of types of backscattered light emitted from the observation target by irradiating the light; and
A light receiving means for receiving backscattered light emitted from the arbitrary layer;
Light intensity acquisition means for acquiring the intensity of light received by the light receiving means;
A light absorption coefficient calculating means for calculating a light absorption coefficient of the arbitrary layer based on the light intensity acquired by the light intensity acquiring means;
Concentration calculating means for calculating the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means ,
The light is a short-time pulsed light, and
Optical path length distribution storage means for storing a model of the propagation optical path length distribution in each of the layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation object;
Time-resolved waveform storage means for storing a model of the time-resolved waveform of the short-time pulsed light irradiated to the observation object;
An optical path length acquisition unit that acquires an optical path length of each of the layers of the plurality of light scattering media at a predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage unit;
A light intensity model obtaining means for obtaining the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage means;
The light intensity obtaining unit obtains the light intensity at a plurality of times t ₁ ~t _m of the optional layer,
The light absorption coefficient calculating means calculates the light absorption coefficient of the arbitrary layer by the following formula (1):

(Where I (t) is the light intensity received by the light receiving means at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light, and Li (t) is the light intensity A concentration quantifying apparatus, which is calculated from an optical path length of the i-th layer at a time t of a model of a propagation optical path length distribution in each layer of a plurality of light scattering media, and μi is a light absorption coefficient of the i-th layer) . A plurality of time the light intensity obtaining unit obtains the light intensity, the concentration quantification device according to claim 1, characterized in that it comprises a plurality of peak time of the propagation path length distribution of each layer of the light-scattering medium. A concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of a plurality of light scattering medium layers,
Irradiation means for irradiating the observation target with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer;
A light scattering medium layer selection means for selecting time-resolved backscattered light emitted from the arbitrary layer from a plurality of types of backscattered light emitted from the observation target by irradiating the light; and
A light receiving means for receiving backscattered light emitted from the arbitrary layer;
Light intensity acquisition means for acquiring the intensity of light received by the light receiving means;
A light absorption coefficient calculating means for calculating a light absorption coefficient of the arbitrary layer based on the light intensity acquired by the light intensity acquiring means;
Concentration calculating means for calculating the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means,
The light is a short-time pulsed light, and
Optical path length distribution storage means for storing a model of the propagation optical path length distribution in each of the layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation object;
Time-resolved waveform storage means for storing a model of the time-resolved waveform of the short-time pulsed light irradiated to the observation object;
From the optical path length distribution storage unit, at a constant time at the model of the propagation optical path length distribution, the optical path length acquisition means for acquiring an optical path length of each layer of the layer of the plurality of light scattering medium,
A light intensity model obtaining means for obtaining the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage means;
The light intensity acquisition means acquires a temporal change in light intensity between a predetermined time and at least a predetermined time τ,
The light absorption coefficient calculating means calculates the light absorption coefficient of the arbitrary layer by the following equation (2):

(Where I (t) is the light intensity received by the light receiving means at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light, and Li (t) is the light intensity The optical path length of the i-th layer at time t in the model of the propagation optical path length distribution in each layer of the plurality of light scattering media, n is the number of layers to be observed, and μi is the light absorption coefficient of the i-th layer. ) can be calculated from the concentration quantification device you characterized. The concentration calculation means calculates the concentration of the target component in the arbitrary layer by the following formula (3)

(Where μa is the light absorption coefficient in the a-th layer which is the arbitrary layer, gj is the molar concentration of the j-th component constituting the observation object, εj is the light absorption coefficient of the j-th component, and p is the observation object. the number of principal components constituting, q is the concentration quantification device according to any one of claims 1 to 3, characterized in that calculated from the a) the number of types of the specific wavelength. A concentration quantification method for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of layers of a plurality of light scattering media,
By irradiating means, the observation object is irradiated with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer,
Next, the light scattering medium layer selection means selects time-resolved backscattered light emitted from the arbitrary layer from a plurality of types of backscattered light emitted from the observation target by irradiating the light. ,
Next, the light receiving means receives backscattered light emitted from the arbitrary layer,
Next, the light intensity acquisition means acquires the intensity of the light received by the light receiving means,
Next, the light absorption coefficient calculation means calculates the light absorption coefficient of the arbitrary layer based on the light intensity acquired by the light intensity acquisition means,
Then, the concentration calculating means calculates the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means ,
The light is a short-time pulsed light, and
The optical path length distribution storage means stores a model of the propagation optical path length distribution in each of the layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation target,
The time-resolved waveform storage means stores a model of the time-resolved waveform of the short-time pulsed light that is irradiated to the observation target,
The optical path length acquisition unit acquires the optical path length of each of the layers of the plurality of light scattering media at a predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage unit,
The light intensity model acquisition means acquires the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage means,
The light intensity obtaining unit obtains the light intensity at a plurality of times t ₁ ~t _m of the optional layer,
The light absorption coefficient calculating means calculates the light absorption coefficient of the arbitrary layer by the following formula (1):

(Where I (t) is the light intensity received by the light receiving means at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light, and Li (t) is the light intensity A concentration quantification method comprising: calculating from the optical path length of the i-th layer at time t of the propagation optical path length distribution model in each layer of the plurality of light scattering media, and μi being a light absorption coefficient of the i-th layer) .   A concentration quantification method for quantifying the concentration of a target component in an arbitrary layer among observation targets composed of layers of a plurality of light scattering media,
  By irradiating means, the observation object is irradiated with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer,
  Next, the light scattering medium layer selection means selects time-resolved backscattered light emitted from the arbitrary layer from a plurality of types of backscattered light emitted from the observation target by irradiating the light. ,
  Next, the light receiving means receives backscattered light emitted from the arbitrary layer,
  Next, the light intensity acquisition means acquires the intensity of the light received by the light receiving means,
  Next, the light absorption coefficient calculation means calculates the light absorption coefficient of the arbitrary layer based on the light intensity acquired by the light intensity acquisition means,
  Then, the concentration calculating means calculates the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means,
  The light is a short-time pulsed light, and
  The optical path length distribution storage means stores a model of the propagation optical path length distribution in each of the layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation target,
  The time-resolved waveform storage means stores a model of the time-resolved waveform of the short-time pulsed light that is irradiated to the observation target,
  The optical path length acquisition unit acquires the optical path length of each of the layers of the plurality of light scattering media at a predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage unit,
  The light intensity model acquisition means acquires the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage means,
  The light intensity acquisition means acquires a temporal change in light intensity between a predetermined time and at least a predetermined time τ,
  The light absorption coefficient calculating means calculates the light absorption coefficient of the arbitrary layer by the following equation (2):

(Where I (t) is the light intensity received by the light receiving means at time t, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light, and Li (t) is the light intensity The optical path length of the i-th layer at time t in the model of the propagation optical path length distribution in each layer of the plurality of light scattering media, n is the number of layers to be observed, and μi is the light absorption coefficient of the i-th layer. The concentration quantification method characterized by calculating from this. In the computer of the concentration quantification device that quantifies the concentration of the target component in any layer among the observation objects composed of multiple layers of light scattering media,
Irradiation procedure for irradiating the observation target with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer,
A light scattering medium layer selection procedure for selecting time-resolved backscattered light emitted from the arbitrary layer from a plurality of types of backscattered light emitted from the observation object by irradiating the light;
A light receiving procedure for receiving backscattered light emitted from the arbitrary layer;
Light intensity acquisition step of acquiring the intensity of the light received by the light receiving procedure,
Based on the light intensity obtained by the light intensity acquisition procedure, the light absorption coefficient calculating step of calculating the light absorption coefficient of the given layer,
On the basis of the light absorption coefficient calculated in the light absorption coefficient calculation procedure, the concentration calculation procedure for calculating the concentration of the target component in the arbitrary layer, allowed to run,
The light is short-time pulsed light;
An optical path length distribution storing procedure for storing a model of a propagation optical path length distribution in each of the layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation object;
A time-resolved waveform storage procedure for storing a model of a time-resolved waveform of the short-time pulsed light irradiated to the observation object;
An optical path for acquiring the optical path length of each of the layers of the plurality of light scattering media at a predetermined time of the propagation optical path length distribution model from the propagation optical path length distribution model stored in the optical path length distribution storing procedure Long acquisition procedure,
Light intensity model acquisition procedure for acquiring the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulse light from the model of the time-resolved waveform of the short-time pulse light stored in the time-resolved waveform storage procedure , Execute
In the light intensity obtaining step to obtain a light intensity at a plurality of times t ₁ ~t _m of the optional layer,
In the light absorption coefficient calculation procedure, the light absorption coefficient of the arbitrary layer is expressed by the following equation (1).

(Where I (t) is the light intensity received at time t in the light receiving procedure, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulsed light, and Li (t) is the above-mentioned A program calculated from a model of a propagation optical path length distribution in each layer of a plurality of light scattering media from an optical path length of the i-th layer at time t, and μi is a light absorption coefficient of the i-th layer) .   In the computer of the concentration quantification device that quantifies the concentration of the target component in any layer among the observation objects composed of multiple layers of light scattering media,
  Irradiation procedure for irradiating the observation target with light having a specific wavelength with a small temperature change in the absorption coefficient of water in the arbitrary layer,
  A light scattering medium layer selection procedure for selecting time-resolved backscattered light emitted from the arbitrary layer from a plurality of types of backscattered light emitted from the observation object by irradiating the light;
  A light receiving procedure for receiving backscattered light emitted from the arbitrary layer;
  A light intensity acquisition procedure for acquiring the intensity of light received in the light reception procedure;
  A light absorption coefficient calculation procedure for calculating a light absorption coefficient of the arbitrary layer based on the light intensity acquired in the light intensity acquisition procedure;
  Based on the light absorption coefficient calculated in the light absorption coefficient calculation procedure, execute a concentration calculation procedure for calculating the concentration of the target component in the arbitrary layer,
  The light is short-time pulsed light;
  An optical path length distribution storing procedure for storing a model of a propagation optical path length distribution in each of the layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation object;
  A time-resolved waveform storage procedure for storing a model of a time-resolved waveform of the short-time pulsed light irradiated to the observation object;
  An optical path for acquiring the optical path length of each of the layers of the plurality of light scattering media at a predetermined time of the propagation optical path length distribution model from the propagation optical path length distribution model stored in the optical path length distribution storing procedure Long acquisition procedure,
  Light intensity model acquisition procedure for acquiring the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulse light from the model of the time-resolved waveform of the short-time pulse light stored in the time-resolved waveform storage procedure , Execute
  In the light intensity acquisition procedure, a time change in light intensity between a predetermined time and at least a predetermined time τ is acquired,
  In the light absorption coefficient calculation procedure, the light absorption coefficient of the arbitrary layer is expressed by the following equation (2).

(Where I (t) is the light intensity received at time t in the light receiving procedure, N (t) is the light intensity at time t of the model of the time-resolved waveform of the short-time pulsed light, and Li (t) is the above-mentioned The optical path length of the i-th layer at time t in the model of the propagation optical path length distribution in each layer of the plurality of light scattering media, n is the number of layers to be observed, and μi is the light absorption coefficient of the i-th layer. ) Is calculated from the program.

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