JP5834704B2 - Concentration determination apparatus, light absorption coefficient calculation method, concentration determination method, program for calculating light absorption coefficient, and program for calculating concentration - Google Patents

Description

  Some aspects of the present invention include a concentration quantification apparatus, a light absorption coefficient calculation method, a concentration quantification method, and a concentration quantification method for quantifying the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers. The present invention relates to a program for calculating a light absorption coefficient and a program for calculating a concentration.

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

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

Japanese Patent No. 3931638

  However, since the conventional non-invasive blood sugar level measurement method measures the near-infrared spectrum of the dermis layer by determining the distance between the light input and output, the measured spectrum includes not only the spectrum of the dermis layer but also the epidermis layer. The spectrum of the subcutaneous tissue layer was also included, and there was a problem that the observed change in the light absorption coefficient included noise due to the epidermis layer or the subcutaneous tissue layer.

  The present invention has been made in view of the above points, and its purpose is to reduce the influence of noise caused by layers other than the target layer, a concentration determination device, a light absorption coefficient calculation method, a concentration determination method, and a light absorption coefficient. To provide a program for calculating and a program for calculating concentration.

According to one aspect of the present invention, propagation of a short-time pulsed light that irradiates a computer to an observation target formed of a plurality of light scattering medium layers in each of the plurality of light scattering medium layers. Optical path length distribution storage means for storing a model of optical path length distribution, time-resolved waveform storage means for storing a model of time-resolved waveform of short-time pulse light irradiated to the observation object, and irradiation to the observation object Optical path length variation storage means for storing variation in optical path length in each of the layers of the plurality of light scattering media, and irradiation means for irradiating the observation target with short-time pulse light, A light receiving unit that receives light back-scattered by the observation target with short-time pulsed light, and the light-receiving unit receives light at a predetermined time after the time when the irradiation unit irradiates short-time pulsed light. An optical path length of each of the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution from the optical intensity acquisition means for acquiring the intensity of the obtained light and the optical path length distribution storage means An optical path length acquisition means for acquiring the light intensity model acquisition means for acquiring 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, and the light intensity The light intensity acquired by the acquisition means, the optical path length of each layer of the plurality of light scattering media acquired by the optical path length acquisition means, the light intensity model acquired by the light intensity model acquisition means, and the optical path Light absorption coefficient calculation means for calculating a light absorption coefficient of an arbitrary layer among the observation targets based on the optical path length variation of each of the layers of the plurality of light scattering media stored in the long variation storage means And A program for calculating the optical absorption coefficient for functioning.
Some aspects of the present invention have been made in order to solve the above-described problem, and a concentration for quantifying the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers. An optical path length distribution storage means 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 means for storing a model of a time-resolved waveform of short-time pulse light irradiated to the observation target; and a plurality of layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation target. Optical path length variation storage means for storing optical path length variation in each layer, irradiation means for irradiating the observation object with short-time pulse light, and light obtained by backscattering the short-time pulse light by the observation object From the light receiving means for receiving light, the light intensity acquisition means for acquiring the intensity of light received by the light receiving means at a predetermined time after the time when the irradiation means irradiated the short-time pulse light, 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 time-resolved waveform model of light; the light intensity acquired by the light intensity acquisition means; and the plurality of lights acquired by the optical path length acquisition means Each of the layers of the plurality of light scattering media stored in the optical path length variation storage unit and the optical path length of each layer of the scattering medium, the light intensity model acquired by the light intensity model acquisition unit A light absorption coefficient calculating means for calculating a light absorption coefficient of the arbitrary layer based on an optical path length variation, and the object in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means. And a concentration calculating means for calculating the concentration of the component.

  According to this configuration, the light intensity of the light received by the light receiving means, the optical path length of each layer at a predetermined time of the propagation path length distribution model, and the light at the predetermined time of the time-resolved waveform model of the short-time pulsed light The light absorption coefficient of an arbitrary layer can be selectively calculated based on the intensity of the light and the optical path length variation of each layer. When calculating the light absorption coefficient, the optical path length variation of each layer is taken into account, so that the calculation result is highly accurate. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), and the light receiving unit The light intensity received at time t is I (t), the light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), When the number of photons is N _in , the incident light intensity is I _in , and the optical path length variation of the m-th layer is δ _km (t), the light intensity acquisition means calculates the light intensity at a plurality of times t _{1 to} t _m . The light absorption coefficient calculating means obtains an approximate solution of the light absorption coefficient of an arbitrary layer from the following equation (1), substitutes the approximate solution for the left side of the following equation (2), and The primary correction value of the light absorption coefficient of the layer is calculated, and the primary correction value is the left side of the following equation (2) By substituting and calculating the second-order correction value of the light absorption coefficient of any layer until it converges to the true value of the light absorption coefficient of any layer, the light absorption coefficient of any layer is calculated. It is characterized by that.

  According to this configuration, when calculating the light absorption coefficient, iterative calculation using the above equations (1) and (2) is performed until the light absorption coefficient converges to a true value. Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), and the light receiving unit The light intensity received at time t is I (t), the light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), When the number of photons is N _in , the incident light intensity is I _in , and the optical path length variation of the m-th layer is δ _km (t), the light intensity acquisition means has at least a predetermined time τ 1 to τ 2 from a predetermined time. The light absorption coefficient calculating means calculates an approximate solution of the light absorption coefficient of an arbitrary layer from the following equation (1) or its integral equation, and the approximate solution is 3) Substituting into the left side of equation, calculate the primary correction value of the light absorption coefficient of any layer Substituting the primary correction value into the left side of the following equation (3) to calculate the secondary correction value of the light absorption coefficient of an arbitrary layer is repeated until the true value of the optical absorption coefficient of the arbitrary layer is converged. Thus, the light absorption coefficient of an arbitrary layer is calculated.

  According to this configuration, when calculating the light absorption coefficient, iterative calculation using the above expressions (1) and (3) is performed until the light absorption coefficient converges to a true value. Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy. Furthermore, since the light absorption coefficient is calculated by the integrated value of the optical path length between the times τ1 and τ2, the influence on the calculation result of the light absorption coefficient due to the error included in the measured light reception intensity can be reduced.

  Further, according to some aspects of the present invention, the concentration calculation unit generates a calibration curve from values obtained by measuring a characteristic whose characteristics are known using multivariate analysis based on the light absorption coefficient in the arbitrary layer. Then, the concentration of the target component in the arbitrary layer is calculated by collating the measurement value of the unknown measurement target with a calibration curve.

  In some embodiments of the present invention, when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified.

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

  Further, some aspects of the present invention provide a light absorption coefficient calculation method for calculating a light absorption coefficient in an arbitrary layer among observation targets formed from a plurality of layers of light scattering media, wherein the observation target includes A model of a propagation optical path length distribution in each of the layers of the plurality of light scattering media, a model of a time-resolved waveform of the short-time pulse light irradiated to the observation target, Variations in the optical path length of each of the layers of the plurality of light scattering media of the short-time pulse light applied to the observation target, and the short time at a predetermined time after the time when the irradiation means irradiates the short-time pulse light. The intensity of light back-scattered by the observation object by the time pulse light, the optical path length of each layer of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution, the short-time pulse A first step of acquiring the light intensity at the predetermined time of the time-resolved waveform model, the light intensity acquired in the first step, and the optical path length of each of the layers of the plurality of light scattering media A second step of calculating a light absorption coefficient of the arbitrary layer based on a light intensity model and an optical path length variation of each of the layers of the plurality of light scattering media. .

  According to this method, the light intensity obtained in the first step, the optical path length of each layer at a predetermined time of the propagation path length distribution model, and the light at the predetermined time of the time-resolved waveform model of the short-time pulsed light The light absorption coefficient of an arbitrary layer can be selectively calculated based on the intensity of the light and the optical path length variation of each layer. When calculating the light absorption coefficient, the optical path length variation of each layer is taken into account, so that the calculation result is highly accurate.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), and the light receiving unit The light intensity received at time t is I (t), the light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), When the number of photons is N _in , the incident light intensity is I _in , and the optical path length variation of the m-th layer is δ _km (t), the light intensity acquisition means acquires the light intensity at a plurality of times t _{1 to} t _m . In the seventh step, an approximate solution of the light absorption coefficient of an arbitrary layer is calculated from the following equation (1), and the approximate solution is substituted into the left side of the following equation (2) to Calculate the primary correction value of the light absorption coefficient, and substitute the primary correction value into the left side of the following equation (2). Calculating the second-order correction value of the light absorption coefficient of an arbitrary layer until it converges to the true value of the light absorption coefficient of the arbitrary layer, thereby calculating the light absorption coefficient of the arbitrary layer. Features.

  According to this method, when calculating the light absorption coefficient, iterative calculation using the above equations (1) and (2) is performed until the light absorption coefficient converges to a true value. Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), and the light receiving unit The light intensity received at time t is I (t), the light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), When the number of photons is N _in , the incident light intensity is I _in , and the optical path length variation of the m-th layer is δ _km (t), in the first step, at least a predetermined time τ 1 to τ 2 from a predetermined time. In the second step, an approximate solution of the light absorption coefficient of an arbitrary layer is calculated from the following equation (1) or its integral equation, and the approximate solution is calculated as (3 ) To calculate the first correction value of the light absorption coefficient of any layer Substituting the primary correction value into the left side of the following equation (3) to calculate the secondary correction value of the light absorption coefficient of an arbitrary layer is repeated until the true value of the optical absorption coefficient of the arbitrary layer is converged. Thus, the light absorption coefficient of an arbitrary layer is calculated.

  According to this method, when calculating the light absorption coefficient, iterative calculation using the above expressions (1) and (3) is performed until the light absorption coefficient converges to a true value. Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy. Furthermore, since the light absorption coefficient is calculated by the integrated value of the optical path length between the times τ1 and τ2, the influence on the calculation result of the light absorption coefficient due to the error included in the measured light reception intensity can be reduced.

  In some embodiments of the present invention, the concentration of the target component in the arbitrary layer is calculated based on the light absorption coefficient calculated in the second step.

  According to this method, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

  In some embodiments of the present invention, when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified.

  According to this method, by calculating the concentration of glucose contained in the dermis layer based on the calculated light absorption coefficient, it is possible to reduce the influence of noise caused by other layers and to accurately determine the concentration of glucose. Can do.

  Further, according to some aspects of the present invention, a propagation optical path in each layer of the plurality of light scattering medium layers of the short-time pulse light irradiated to the observation target formed from the plurality of light scattering medium layers Optical path length distribution storage means for storing a model of long distribution, time-resolved waveform storage means for storing a model of time-resolved waveform of short-time pulse light irradiated to the observation object, and irradiation to the observation object Optical path length variation storage means for storing variation in optical path length in each of the layers of the plurality of light scattering media of short-time pulse light, and the concentration of the target component in any layer of the observation target A concentration quantification apparatus for quantifying comprises: an irradiating means for irradiating the observation object with a short-time pulsed light; a light receiving means for receiving the light backscattered by the observation object with the short-time pulsed light; and the irradiating means for a short time From the light intensity acquisition means for acquiring the intensity of light received by the light receiving means at a predetermined time after the light irradiation time, the optical path length distribution storage means from the optical path length distribution model at the predetermined time Light at a predetermined time of a model of the time-resolved waveform of the short-time pulsed light from the time-resolved waveform storage means, the optical path length acquisition means for acquiring the optical path length of each of the layers of the plurality of light scattering media A light intensity model acquisition means for acquiring the light intensity, a light intensity acquired by the light intensity acquisition means, an optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition means, and the light Based on the light intensity model acquired by the intensity model acquisition unit and the optical path length variation of each of the layers of the plurality of light scattering media stored in the optical path length variation storage unit, the light of the arbitrary layer Light absorption coefficient calculating means for calculating the yield factor, is a program to calculate the optical absorption coefficient for operating as.

  According to this program, the light intensity of the light received by the light receiving means, the optical path length of each layer at a predetermined time of the propagation path length distribution model, and the light at the predetermined time of the time-resolved waveform model of the short-time pulsed light The light absorption coefficient of an arbitrary layer can be selectively calculated based on the intensity of the light and the optical path length variation of each layer. When calculating the light absorption coefficient, the optical path length variation of each layer is taken into account, so that the calculation result is highly accurate.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), and the light receiving unit The light intensity received at time t is I (t), the light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), When the number of photons is N _in , the incident light intensity is I _in , and the optical path length variation of the m-th layer is δ _km (t), the light intensity acquisition means calculates the light intensity at a plurality of times t _{1 to} t _m . The light absorption coefficient calculating means obtains an approximate solution of the light absorption coefficient of an arbitrary layer from the following equation (1), substitutes the approximate solution for the left side of the following equation (2), and The primary correction value of the light absorption coefficient of the layer is calculated, and the primary correction value is the left side of the following equation (2) By substituting and calculating the second-order correction value of the light absorption coefficient of any layer until it converges to the true value of the light absorption coefficient of any layer, the light absorption coefficient of any layer is calculated. It is characterized by that.

  According to this program, when calculating the light absorption coefficient, iterative calculation using the above equations (1) and (2) is performed until the light absorption coefficient converges to a true value. Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), and the light receiving unit The light intensity received at time t is I (t), the light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), When the number of photons is N _in , the incident light intensity is I _in , and the optical path length variation of the m-th layer is δ _km (t), the light intensity acquisition means has at least a predetermined time τ 1 to τ 2 from a predetermined time. The light absorption coefficient calculating means calculates an approximate solution of the light absorption coefficient of an arbitrary layer from the following equation (1) or its integral equation, and the approximate solution is 3) Substituting into the left side of equation, calculate the primary correction value of the light absorption coefficient of any layer Substituting the primary correction value into the left side of the following equation (3) to calculate the secondary correction value of the light absorption coefficient of an arbitrary layer is repeated until the true value of the optical absorption coefficient of the arbitrary layer is converged. Thus, the light absorption coefficient of an arbitrary layer is calculated.

  According to this program, when calculating the light absorption coefficient, iterative calculation using the above expressions (1) and (3) is performed until the light absorption coefficient converges to a true value. Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy. Furthermore, since the light absorption coefficient is calculated by the integrated value of the optical path length between the times τ1 and τ2, the influence on the calculation result of the light absorption coefficient due to the error included in the measured light reception intensity can be reduced.

  Further, according to some aspects of the present invention, a concentration for operating as a concentration calculating unit that calculates the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating unit. This is a program that performs calculation.

  According to this program, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

  In some embodiments of the present invention, when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified.

  According to this program, by calculating the concentration of glucose contained in the dermis layer based on the calculated light absorption coefficient, the influence of noise by other layers can be reduced, and the concentration of glucose can be determined with high accuracy. Can do.

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

  Embodiments of the present invention will be described below with reference to the drawings.

(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 device 100 (concentration determination device) includes a simulation unit 101, an optical path length distribution storage unit 102 (optical path length distribution storage unit), a time-resolved waveform storage unit 103 (time-resolved waveform storage unit), and an optical path length variation storage unit 104. (Optical path length variation storage means), irradiating section 105 (irradiating means), light receiving section 106 (light receiving means), measured light intensity acquisition section 107 (light intensity acquisition means), measured light intensity storage section 108, optical path length acquisition section 109 ( Optical path length acquisition unit), non-absorption light intensity acquisition unit 110 (light intensity model acquisition unit), light absorption coefficient calculation unit 111 (light absorption coefficient calculation unit), component absorption information storage unit 112, concentration calculation unit 113 (concentration calculation unit) ), A density unit conversion unit 114, and a density display unit 115.

  The blood glucose level measuring apparatus 100 measures the concentration of glucose (target component) contained in the dermis layer (arbitrary layer) of the skin (observation target).

The simulation part 101 performs the simulation which irradiates light with respect to the skin model whose light absorption coefficient is zero. The simulation is performed using, for example, a Monte Carlo method.
The optical path length distribution storage unit 102 stores a propagation optical path length distribution of a skin model having a light absorption coefficient of zero.
The time-resolved waveform storage unit 103 stores a time-resolved waveform of a skin model having a light absorption coefficient of zero.
The optical path length variation storage unit 104 stores the optical path length variation of the skin model whose light absorption coefficient is zero. Here, “optical path length variation” means the average value per one photon of the distance propagated through the dermis layer of all photons detected at a predetermined time and the dermis layer of one photon detected at the predetermined time. It is the difference with the distance.

  The irradiation unit 105 irradiates the skin with short-time pulsed light. The plurality of short-time pulse lights emitted by the irradiating unit 105 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 106 receives light obtained by backscattering the short-time pulsed light by the skin.
The measurement light intensity acquisition unit 107 acquires the light intensity at a certain time of the light received by the light receiving unit 106.
The measurement light intensity storage unit 108 stores the light intensity at a certain time acquired by the measurement light intensity acquisition unit 107.

The optical path length acquisition unit 109 acquires the optical path length at a certain time from the optical path length distribution storage unit 102.
The non-absorption light intensity acquisition unit 110 acquires the light intensity at a certain time from the time-resolved waveform storage unit 103.

The light absorption coefficient calculation unit 111 calculates the light absorption coefficient in the dermis layer of the skin irradiated with the short-time pulse light.
The component absorption information storage unit 112 stores in advance the light absorption coefficient or molar absorption coefficient of the main component of the skin.

The concentration calculation unit 113 calculates the concentration of glucose contained in the dermis layer.
The concentration unit converter 114 converts the glucose concentration unit into a desired unit.
The concentration display unit 115 displays the glucose concentration.

  In the blood glucose level measuring apparatus 100 of the present embodiment, the irradiation unit 105 irradiates the skin with a short-time pulse light, the light-receiving unit 106 receives the light back-scattered by the short-time pulse light by the skin, and the measurement light intensity acquisition unit 107 acquires the intensity of light received by the light receiving unit 106 at time t. Next, the optical path length acquisition unit 109 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 102, and the non-absorbing light intensity acquisition unit 110 stores the time-resolved waveform storage unit From 103, the light intensity at time t of the time-resolved waveform of the short-time pulsed light in the skin model is acquired.

  Next, the light absorption coefficient calculation unit 111 acquires the light intensity stored in the measured light intensity storage unit 108, the optical path length of each skin layer acquired by the optical path length acquisition unit 109, and the non-absorption light intensity acquisition unit 110. Based on the measured light intensity and the optical path length variation stored in the optical path length variation storage unit 104, the light absorption coefficient of the dermis layer of the skin is calculated. Then, the concentration calculation unit 113 calculates the glucose concentration in the dermis layer based on the light absorption coefficient calculated by the light absorption coefficient calculation unit 111.

  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. The glucose concentration calculated by the concentration calculation unit 113 is converted into a desired unit by the concentration unit conversion unit 114 and displayed on the concentration display unit 115.

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

When generating the skin model, the simulation unit 101 performs a simulation of irradiating the skin model with light. At this time, it is necessary to determine the distance between the position of the irradiation unit 105 and the position of the light receiving unit 106. The simulation is preferably performed using the Monte Carlo method. The simulation by the Monte Carlo method is performed as follows, for example.
First, the simulation unit 101 performs calculation for irradiating a skin model with a photon (light beam) as a model of light to be irradiated. Photons irradiated to the skin model move in the skin model. At this time, the photon determines the distance L and the direction θ to the next advancing point by a random number R (0 ≦ R ≦ 1). The simulation unit 101 calculates the distance L to the point where the photon advances next by the equation (10).

Here, ln (A) represents the natural logarithm of A. Μ _sm represents the scattering coefficient of the mth layer (any 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 to the next point according to the equation (11).

However, g shows the anisotropic parameter which is the average of the cosine 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 105 to the light receiving unit 106 by repeating the calculations of the above equations (10) and (11) every unit time. The simulation unit 101 calculates a movement distance for a plurality of photons. For example, the simulation unit 101 calculates the movement distance for 10 ⁸ photons.

FIG. 2 is a graph showing the propagation optical path length distribution of each layer (skin layer, dermis layer, subcutaneous tissue layer) calculated by the simulation unit.
The horizontal axis of FIG. 2 shows the elapsed time from photon irradiation, and the vertical axis shows the logarithmic display of the optical path length. The simulation unit 101 classifies each movement path of photons that have reached the light receiving unit 106 for each layer through which the movement path passes. The simulation unit 101 calculates the propagation path length distribution of each layer of the skin as shown in FIG. 2 by calculating the average length of the movement path of the photons that arrived per unit time for each classified layer.

FIG. 3 is a graph showing a time-resolved waveform calculated by the simulation unit.
The horizontal axis in FIG. 3 indicates the elapsed time from the photon irradiation, and the vertical axis indicates the number of photons detected by the light receiving unit 106. The simulation unit 101 calculates the time-resolved waveform of the skin model as shown in FIG. 3 by calculating the number of photons reaching the light receiving unit 106 per unit time.
Through the processing described above, the simulation unit 101 calculates the propagation optical path length distribution and time-resolved waveform of the skin model for a plurality of wavelengths. At this time, the simulation unit 101 may calculate the propagation optical path length distribution and the time-resolved waveform with respect to the wavelength at which the orthogonality of the absorption spectrum of the skin main components (water, protein, lipid, glucose, etc.) becomes high.

FIG. 4 is a graph showing the absorption spectrum of the main component of the skin.
The horizontal axis in FIG. 4 indicates the wavelength of light to be irradiated, and the vertical axis indicates the light absorption coefficient. Referring to FIG. 4, the light absorption coefficient of glucose becomes maximum when the wavelength is 1600 nm, and the light absorption coefficient of water becomes maximum when the wavelength is 1450 nm. For this reason, the simulation unit 101 may calculate the propagation optical path length distribution and the time-resolved waveform with respect to a wavelength at which the orthogonality of the absorption spectrum of the main component of skin, such as 1450 nm and 1600 nm, becomes high.

Next, the optical path length variation of the skin model will be described.
After calculating the movement distance for the plurality of photons calculated by the simulation unit 101, the optical path length variation of the skin model is calculated based on the calculation result. For example, the moving distance l _km (t) of each layer of each photon is stored. The optical path length variation δ _km (t) is calculated based on the following equations (12) and (13) after the simulation is completed.

  When the simulation unit 101 calculates the propagation optical path length distribution, time-resolved waveform, and optical path length variation of the skin model for a plurality of wavelengths, the information on the propagation optical path length distribution is stored in the optical path length distribution storage unit 102, and the time-resolved waveform information is stored. Is stored in the time-resolved waveform storage unit 103, and information on optical path length variation is stored in the optical path length variation storage unit 104.

Next, the operation in which the blood sugar level measuring apparatus 100 measures the blood sugar level will be described.
FIG. 5 is a first flowchart showing an operation in which the blood sugar level measuring apparatus measures the blood sugar level.
First, when the user places the blood glucose level measuring device 100 on the skin and operates the blood glucose level measuring device 100 by pressing a measurement start switch (not shown) or the like, the irradiation unit 105 shortens the wavelength λ ₁ with respect to the skin. Time pulse light is irradiated (step S1). Here, the wavelength λ ₁ is _one of a plurality of wavelengths calculated by the simulation unit 101 for the propagation optical path length distribution and the time-resolved waveform.

  When the irradiating unit 105 irradiates the pulsed light for a short time, the light receiving unit 106 receives the light irradiated from the irradiating unit 105 and backscattered by the skin (step S2). At this time, the light receiving unit 106 registers the received light intensity for each unit time (for example, every 1 picosecond) from the start of irradiation in the internal memory.

When the light receiving unit 106 completes the light reception, the measurement light intensity acquisition unit 107 acquires the same number of received light intensity I (t) at different times t stored in the internal memory of the light receiving unit 106 as the number of skin layers. (Step S3). That is, the measurement light intensity acquisition unit 107 acquires the received light intensity I (t ₁ ) to I (t ₃ ) at _three different times t _{1 to} t ₃ . Here, the reason why the received light intensity is obtained by the same number as the number of skin layers is to calculate the light absorption coefficient of each skin layer by simultaneous equations in the processing described later. The received light intensity acquired by the measurement light intensity acquisition unit 107 is stored in the measurement light intensity storage unit 108.

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

When the measurement light intensity acquisition unit 107 acquires the received light intensities I (t ₁ ) to I (t ₃ ), the optical path length acquisition unit 109 calculates from the propagation optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 102. , the optical path length of each layer of the skin at time _{t 1 ~t 3 L 1 (t} 1) ~L 1 (t 3), L 2 (t 1) ~L 2 (t 3), L 3 (t 1) ~L ₃ (t ₃ ) is acquired (step S4).

When the measurement light intensity acquisition unit 107 acquires the received light intensities I (t ₁ ) to I (t ₃ ), the non-absorption light intensity acquisition unit 110 stores the time of the wavelength λ ₁ stored in the time-resolved waveform storage unit 103. from degradation waveform, time _t 1 detected in ~t ₃ photon number _{N (t 1) ~N (t} 3) to get (step S5).

In the present embodiment, the light absorption coefficient calculation unit 111 first calculates an approximate solution of the light absorption coefficient of an arbitrary layer from the following equation (1). Then, the approximate solution is substituted into the left side of the following equation (2) to calculate the primary correction value of the light absorption coefficient of an arbitrary layer. Then, substituting the primary correction value into the left side of the following equation (2) to calculate the secondary correction value of the light absorption coefficient of an arbitrary layer until convergence to the true value of the light absorption coefficient of the arbitrary layer Repeat. Thereby, the light absorption coefficient of an arbitrary layer is calculated. However, the natural logarithm is ln (•), the light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t), and the light intensity received by the light receiving means at time t is I (t), The optical absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), the number of incident photons is N _in , the incident light intensity is I _in , The optical path length variation of the m layer is assumed to be δ _km (t).

Here, the derivation process of the equations (1) and (2) will be described.
In the time-resolved waveform of backscattered light obtained by the incidence of short-time pulsed light on the skin, the light received at a relatively early time passes only through the shallower part from the skin surface. Conversely, the light received at a relatively late time reaches a deeper region from the surface of the skin. Thus, the received light intensity at different times corresponds to the light components propagated through different path distributions. That is, the light intensity at a certain time includes light absorption information in the light path distribution corresponding to the time. Therefore, if the optical path for each detection time of the time-resolved waveform is obtained in advance by simulation or actual measurement, the spatial distribution of the light absorption coefficient can be estimated by the inverse problem solving method. Based on this principle, the present invention reconstructs the internal absorption distribution based on the time-resolved waveform of the backscattered light from the scatterer, and obtains the substance concentration from the absorption distribution.

Light incident on the living body from the irradiation unit propagates while repeating the scattering process, and is received by the light receiving unit. It can be considered that the light that has reached the light receiving section selectively passes through a local site (here, each layer) in the living body depending on the detection time. In the present invention, it is assumed that the propagation path of photons in a living body is characterized by a scattering coefficient, and the change in light intensity along the optical path is characterized by a light absorption coefficient. Here, when the light intensity I (t) detected at time t is normalized by the incident light intensity I _in , the intensity at the time of incidence of the kth photon detected at time t of the time-resolved waveform is 1. When the light intensity is i _k (t), the number of incident photons is N _in , and the number of photons detected at time t is N (t), the following equation (14) is obtained.

  Note that a photon is not a single quantum mechanical photon but a photon bundle having continuously decaying energy.

Further, i _k (t) is expressed as the following formula (15) as the sum of microscopic Beer-Lambert rules.

Here, l is the moving distance, c _s of photons in vivo is the velocity of light in vivo.

Next, consider a case where the light absorption coefficient in the living body is different in each layer. When the total number of layers is n, the light absorption coefficient in the m-th layer is μ _am , and the distance that the k-th photon has passed through each layer is 1 _km , the above equation (15) becomes the following equation (16): .

  Therefore, the following equation (17) is obtained from the above equations (14) and (16).

Here, the variation in the propagation path for each detected photon is considered. In that case, the detected light intensity time waveform I (t) is detected at an average value L _m ′ (t) per one photon of the distance propagated through the m-th layer of all photons detected at time t and at time t. By introducing the difference δ _km (t) from the distance l _km (t) propagated through the m-th layer of the k-th photon, the following equation (18) is obtained.

  When the above equation (18) is modified, the following equation (19) is obtained.

Further, when L _m ′ (t) is expressed by using the total (= optical path length distribution) L _m (t) of the detected photon number N (t) of the distance propagated through the m-th layer, the following equation (13) Become.

Therefore, the above expression (19) becomes the following expression (2) when expressed using L _m (t).

  In this way, equation (2) is derived.

  The above formula (2) is a general formula. When the equation (2) is modified to be applied to the three-layer structure in the present embodiment, the following equation (20) is obtained.

  As for the above equation (18), when the Taylor expansion is performed for the exp function according to the following equation (22) from the formula for the Taylor expansion of the following equation (21), the equation (18) is expressed as the following equation (23): Become.

  When the above equation (23) is arranged, the following equation (24) is obtained.

Here, since δ _km (t) is zero for all photons, the primary term of equation (24) is 0 as shown in equation (25) below.

  Further, if the second-order or higher term of the above equation (25) is approximated as sufficiently small, the following equation (26) is obtained.

If the above equation (26) is rearranged and further expressed using L _m (t) using the above equation (13), the following equation (1) is obtained.

  In this way, equation (1) is derived.

  The above formula (1) is a general formula. When the equation (1) is modified so as to be applied to the three-layer structure in the present embodiment, the following equation (27) is obtained.

Returning to FIG. 5, when the optical path length acquisition unit 109 acquires the optical path length of each layer of the skin and the non-absorption light intensity acquisition unit 110 acquires the number of detected photons, the light absorption coefficient calculation unit 111 calculates the equation (1). Based on the equation (27) applied to the three-layer structure of the embodiment (step S6), the initial values of the light absorption coefficients μ _{1 to} μ ₃ of each layer of the skin are calculated (step S7). Here, the light absorption coefficient μ _a1 represents the light absorption coefficient of the epidermis layer, the light absorption coefficient μ _a2 represents the light absorption coefficient of the dermis layer, and the light absorption coefficient μ _a3 represents the light absorption coefficient of the subcutaneous tissue layer.

Here, ln (A) represents the natural logarithm of A. I _in indicates the light intensity of the short-time pulse light emitted by the irradiation unit 105. N _in indicates the number of photons for which the simulation unit 101 has simulated irradiation.

When the light absorption coefficient calculation unit 111 calculates the initial values of the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin, the light absorption coefficient calculation unit 111 emits light for the same number of wavelengths as the number of types of main components of the skin. It is determined whether or not the initial values of the absorption coefficients μ _{a1 to} μ _a3 have been calculated (step S8). In the present embodiment, since the blood sugar level is measured with four types of main components of the skin, water, protein, lipid, and glucose, the light absorption coefficient calculation unit 111 performs light for four wavelengths λ _{1 to} λ ₄ . It is determined whether or not the absorption coefficients μ _{1 to} μ ₃ are calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 101 for the propagation optical path length distribution and the time-resolved waveform.

When the light absorption coefficient calculating unit 111 determines that there are wavelengths λ _{1 to} λ ₄ for which the initial values of the light absorption coefficients μ _{a1 to} μ _a3 are not calculated (step S8: NO), the process returns to step S1 and still light The initial values of the light absorption coefficients μ _{a1 to} μ _a3 of the wavelengths λ _{1 to} λ ₄ for which the initial values of the absorption coefficients μ _{a1 to} μ _a3 are not calculated are calculated.

On the other hand, when the light absorption coefficient calculation unit 111 determines that the initial values of the light absorption coefficients μ _{a1 to} μ _a3 of the wavelengths λ _{1 to} λ ₄ are calculated (step S8: YES), the light absorption coefficient calculation unit 111 Calculates the correction values of the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin based on the expression (20) obtained by applying the expression (2) to the three-layer structure of the present embodiment (step S10) (step S11). ).

Here, the calculation of the correction value is repeated. Specifically, the initial value of the light absorption coefficient μ _{1 to} μ ₃ of each layer of skin, that is, the approximate solution is substituted into the left side of the above equation (20), and the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin After calculating the primary correction value, the primary correction value is substituted into the left side of the above equation (20) to calculate the secondary correction values of the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin. The calculation of the correction value is repeatedly performed until it converges to the true value of the light absorption coefficient.

  Note that the number of repetitions may be repeated until the amount of change between the previous calculated value (for example, the primary correction value) and the current calculated value (for example, the secondary correction value) falls below a certain amount. Further, the number of repetitions may be set in advance.

Here, using the above equation (20), a description will be given of the abort determination when performing repeated calculations. An example is blood glucose measurement. Judgment is made based on the following assumptions.
Simplify the model and consider an aqueous glucose solution. The accuracy required for blood glucose level measurement at a medical site is ± 10 mg / dl. Light of 1600 nm near the absorption peak of the glucose absorption spectrum is used for the measurement. The light absorption coefficient of water at 1600 nm is 0.7 / mm, and the light absorption coefficient of glucose is 1.3 / mm. The volume fraction of the 10 mg / dl glucose aqueous solution is set to 6.2 × 10 ⁻⁵ . Light absorption coefficient of glucose aqueous solution mu _a is expressed by (28) below.

Here, μ _ag is the light absorption coefficient of glucose, μ _aw is the light absorption coefficient of water, c _vg is the volume fraction (volume concentration) of glucose, and _{cv w} is the volume fraction of water (volume concentration).

  When calculated under the above conditions, the light absorption coefficient of the glucose aqueous solution produced by the fluctuation of glucose 10 mg / dl is about 0.000037. That is, in order to determine the glucose concentration ± 10 mg / dl, the light absorption coefficient ± 0.000037 must be discriminated. Therefore, regarding the abortion determination when performing repeated calculations, if the number of the fifth decimal place in the calculation result does not fluctuate over several to about 10 calculations, it may be regarded as converged. .

Returning to FIG. 5, when it is determined that the light absorption coefficients μ _{a1 to} μ _a3 have not converged to the true values (step S12: NO), the process returns to step S10 and the correction values of the light absorption coefficients μ _{1 to} μ ₃ are calculated. I do.

On the other hand, when it is determined that the light absorption coefficients μ _{a1 to} μ _a3 have converged to the true values (step S12: YES), the light absorption coefficient calculation unit 111 acquires the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin. (Step S13). Since the light absorption coefficients μ _{a1 to} μ _a3 need to be acquired for the wavelengths λ _{1 to} λ ₄ , the same procedure is performed for each wavelength (step S14). When the light absorption coefficients μ _{a1 to} μ _a3 can be acquired for the wavelengths λ _{1 to} λ ₄ , the concentration calculation unit 113 calculates the concentration of glucose contained in the dermis based on the equation (29) (step S15).

Here, the light absorption coefficient in the m-th layer is μ _am , the light absorption coefficient of the i-th component forming the skin is μ _ai , and the volume concentration of the i-th component forming the skin is c _vi .
The above formula (29) is a general formula. When the equation (29) is modified to apply to the four wavelengths in the present embodiment, the following equation (30) is obtained.

However, μ _a2 (λ) is the optical absorption coefficient of the wavelength lambda ₁ to [lambda] ₄ in the dermis layer, μ _aw (λ) is the optical absorption coefficient of water in the wavelength lambda ₁ to [lambda] ₄ in the dermis layer, μ _ap (λ) is The light absorption coefficient of the protein with wavelengths λ _{1 to} λ ₄ in the dermis layer, μ _al (λ) is the light absorption coefficient of the lipid with wavelengths λ _{1 to} λ ₄ in the dermis layer, and μ _ag (λ) is the wavelength λ ₁ in the dermis layer. The light absorption coefficient of glucose of ˜λ ₄ is shown. C _vw is the volume concentration of water (volume fraction), c _vp is the volume concentration of protein (volume fraction), c _vl is the volume concentration of lipid (volume fraction), and c _vg is the volume concentration of volume (volume). Fraction).

The concentration calculation unit 113 calculates glucose from the light absorption coefficient of the main component in the measurement target stored in the component absorption information storage unit 112 and the light absorption coefficient μ _a2 in the dermis layer calculated by the above equation (30). The concentration of is calculated.

  Note that the glucose concentration may be calculated using the following equation (31) instead of the above equation (29).

However, the light absorption coefficient in the m-th layer is μ _am , the molar extinction coefficient of the i-th component forming the skin is ε _i , and the molar concentration of the i-th component forming the skin is c _i .
The above formula (31) is a general formula. When the equation (31) is modified to be applied to the three-layer structure in the present embodiment, the following equation (32) is obtained.

Where ε _w (λ) is the molar extinction coefficient of water of wavelengths λ _{1 to} λ ₄ in the dermis layer, ε _p (λ) is the molar extinction coefficient of protein of wavelengths λ _{1 to} λ ₄ in the dermis layer, and ε _l (λ ) Represents the molar extinction coefficient of lipids with wavelengths λ _{1 to} λ ₄ in the dermis layer, and ε _g (λ) represents the molar extinction coefficient of glucose with wavelengths λ _{1 to} λ ₄ in the dermis layer. Further, c _w represents molar concentration of water, c _p is the molar concentration of the protein, c _l is the molar concentration of the lipid, c _g is the molar concentration of glucose.

  The concentration calculation unit 113 calculates the glucose concentration from the molar extinction coefficient of the main component in the measurement target stored in the component absorption information storage unit 112 and the molar extinction coefficient ε in the dermis layer calculated by the above equation (32). Calculate the concentration.

  The concentration unit converter 114 converts the unit of glucose concentration calculated by the concentration calculator 113 into a desired unit. The concentration display unit 115 displays the glucose concentration.

  As described above, according to this embodiment, the skin is irradiated with pulsed light for a short time, the intensity of the light received at a predetermined time, the optical path length of each layer at the predetermined time of the model of the propagation optical path length distribution, and the short The light absorption coefficient of the dermis layer can be selectively calculated based on the light intensity at a predetermined time of the time-resolved waveform model of the time pulse light and the optical path length variation of each layer. If the optical path length variation of each layer is not taken into account when calculating the light absorption coefficient, the obtained result is an approximate solution, and it corresponds to the case where a highly accurate detection result is required such as when the content of the target component is low It becomes difficult. On the other hand, in this embodiment, since the optical path length variation of each layer is taken into consideration, the calculation result is highly accurate. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

  In addition, according to the present embodiment, when calculating the light absorption coefficient, iterative calculation using the above formulas (1) and (2) is performed until the light absorption coefficient converges to a true value. Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy.

(Second Embodiment)
Next, a second embodiment of the present invention will be described in detail.
The second embodiment has the same configuration as the blood glucose level measuring apparatus 100 according to the first embodiment, and includes a measurement light intensity acquisition unit 107, an optical path length acquisition unit 109, a non-absorption light intensity acquisition unit 110, and a light absorption coefficient calculation unit. 111 operations are different.

FIG. 6 is a second flowchart showing an operation in which the blood sugar level measuring apparatus measures the blood sugar level.
First, when the blood sugar level measuring apparatus 100 is operated, the irradiating unit 105 irradiates the skin with short-time pulsed light having a wavelength λ ₁ (step S21). Here, the wavelength λ ₁ is _one of a plurality of wavelengths calculated by the simulation unit 101 for the propagation optical path length distribution and the time-resolved waveform.

When the irradiation unit 105 irradiates the pulsed light for a short time, the light receiving unit 106 receives the light irradiated from the irradiation unit 105 and back-scattered by the skin (step S22). At this time, the light receiving unit 106 registers the received light intensity for each unit time (for example, every 1 picosecond) from the start of irradiation in the internal memory.
When the light receiving unit 106 completes the light reception, the measurement light intensity acquisition unit 107 acquires a time distribution of the light reception intensity during a certain time τ1 to τ2 from the light reception intensity stored in the internal memory of the light reception unit 106 (step) S23).

When the measurement light intensity acquisition unit 107 acquires the time distribution of the received light intensity during the time τ1 to τ2, the optical path length acquisition unit 109 calculates from the propagation optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 102. The optical path lengths L _{1 to} L ₃ of each layer of the skin during a certain time τ _{1 to} τ ₂ are acquired (step S 24).
Further, when the measurement light intensity acquisition unit 107 acquires the received light intensity during the time τ1 to τ2, the non-absorption light intensity acquisition unit 110 calculates the time-resolved waveform of the wavelength λ ₁ stored in the time-resolved waveform storage unit 103 from The number of detected photons between a certain time τ1 and τ2 is acquired (step S25).

In the present embodiment, the light absorption coefficient calculation unit 111 first calculates an approximate solution of the light absorption coefficient of an arbitrary layer from the following equation (1) or its integral equation. Next, the approximate solution is substituted into the left side of the following equation (3) to calculate a primary correction value of the light absorption coefficient of an arbitrary layer. Then, substituting the primary correction value into the left side of the following equation (3) to calculate the secondary correction value of the light absorption coefficient of an arbitrary layer until convergence to the true value of the light absorption coefficient of the arbitrary layer Repeat. Thereby, the light absorption coefficient of an arbitrary layer is calculated. However, the natural logarithm is ln (·), the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), the light intensity received by the light receiving unit 106 at time t is I (t), The light absorption coefficient of the m layer is μ _am , the optical path length of the m-th layer at time t in the propagation optical path length distribution model is L _m (t), the number of incident photons is N _in , the incident light intensity is I _in , and the m-th layer Is represented by δ _km (t).

  The above formula (1) is a general formula. When the equation (1) is modified so as to be applied to the three-layer structure in the present embodiment, the following equation (27) is obtained.

  Further, the above expression (3) is an expression obtained by developing the expression (2) used in the first embodiment into an integral type. The above formula (3) is a general formula. When the equation (3) is modified so as to be applied to the three-layer structure in the present embodiment, the following equation (33) is obtained.

Returning to FIG. 5, when the optical path length acquisition unit 109 acquires the optical path length of each layer of the skin and the non-absorption light intensity acquisition unit 110 acquires the number of detected photons, the light absorption coefficient calculation unit 111 calculates the equation (1). Based on the above equation (27) applied to the three-layer structure of the embodiment (step S26), the initial values of the light absorption coefficients μ _{a1 to} μ _a3 of the skin layers are calculated (step S27). Here, the light absorption coefficient μ _a1 represents the light absorption coefficient of the epidermis layer, the light absorption coefficient μ _a2 represents the light absorption coefficient of the dermis layer, and the light absorption coefficient μ _a3 represents the light absorption coefficient of the subcutaneous tissue layer.

Here, ln (A) represents the natural logarithm of A. I _in indicates the light intensity of the short-time pulse light emitted by the irradiation unit 105. N _in indicates the number of photons for which the simulation unit 101 has simulated irradiation.

When the light absorption coefficient calculation unit 111 calculates the initial values of the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin, the light absorption coefficient calculation unit 111 emits light for the same number of wavelengths as the number of types of main components of the skin. It is determined whether or not the initial values of the absorption coefficients μ _{a1 to} μ _a3 have been calculated (step S28). In the present embodiment, since the blood sugar level is measured with four types of main components of the skin, water, protein, lipid, and glucose, the light absorption coefficient calculation unit 111 performs light for four wavelengths λ _{1 to} λ ₄ . It is determined whether or not the initial values of the absorption coefficients μ _{a1 to} μ _a3 have been calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 101 for the propagation optical path length distribution and the time-resolved waveform.

If the light absorption coefficient calculation unit 111 determines that there are wavelengths λ _{1 to} λ ₄ for which the initial values of the light absorption coefficients μ _{a1 to} μ _a3 are not calculated (step S28: NO), the process returns to step S1 and still light The initial values of the light absorption coefficients μ _{a1 to} μ _a3 of the wavelengths λ _{1 to} λ ₄ for which the initial values of the absorption coefficients μ _{a1 to} μ _a3 are not calculated are calculated.

On the other hand, when the light absorption coefficient calculation unit 111 determines that the initial values of the light absorption coefficients μ _{a1 to} μ _a3 of the wavelengths λ _{1 to} λ ₄ are calculated (step S28: YES), the light absorption coefficient calculation unit 111 Calculates the correction value of the light absorption coefficient μ _{a1 to} μ _a3 of each layer of the skin based on the above equation (33) in which the equation (3) is applied to the three-layer structure of the present embodiment (step S30) ( Step S31).

Here, the calculation of the correction value is repeated. Specifically, the initial value of the light absorption coefficient μ _{a1 to} μ _a3 of each layer of skin, that is, the approximate solution is substituted into the left side of the above equation (33), and the light absorption coefficient μ _{a1 to} μ _a3 of each layer of the skin After calculating the primary correction value, the secondary correction value of the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin is calculated by substituting the primary correction value into the left side of the above equation (33). The calculation of the correction value is repeatedly performed until it converges to the true value of the light absorption coefficient.

  Note that the number of repetitions may be repeated until the amount of change between the previous calculated value (for example, the primary correction value) and the current calculated value (for example, the secondary correction value) falls below a certain amount. Further, the number of repetitions may be set in advance.

When it is determined that the light absorption coefficients μ _{a1 to} μ _a3 have not converged to the true values (step S32: NO), the process returns to step S30, and correction values of the light absorption coefficients μ _{a1 to} μ _a3 are calculated.

On the other hand, when it is determined that the light absorption coefficients μ _{a1 to} μ _a3 have converged to the true values (step S32: YES), the light absorption coefficient calculation unit 111 acquires the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin. (Step S33). Since the light absorption coefficients μ _{a1 to} μ _a3 need to be acquired for the wavelengths λ _{1 to} λ ₄ , the same procedure is performed for each wavelength (step S34). When the light absorption coefficients μ _{a1 to} μ _a3 can be acquired for the wavelengths λ _{1 to} λ ₄ , the concentration calculation unit 113 applies the above formula (29) to the above four wavelengths in the present embodiment (30). Based on the above, the concentration of glucose contained in the dermis is calculated (step S35).

The concentration calculation unit 113 calculates glucose from the light absorption coefficient of the main component in the measurement target stored in the component absorption information storage unit 112 and the light absorption coefficient μ _a2 in the dermis layer calculated by the above equation (30). The concentration of is calculated.

  The concentration calculation unit 113 uses the molar extinction coefficient of the main component in the measurement target stored in the component absorption information storage unit 112 and the molar extinction coefficient ε in the dermis layer calculated by the above equation (32). The concentration of glucose may be calculated.

  The concentration unit converter 114 converts the unit of glucose concentration calculated by the concentration calculator 113 into a desired unit. The concentration display unit 115 displays the glucose concentration.

  Thus, also in this embodiment, since the optical path length variation of each layer is taken into consideration, the calculation result of the light absorption coefficient of the dermis layer is highly accurate. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

  Further, according to the present embodiment, when calculating the light absorption coefficient, iterative calculation is performed using the above expressions (1) and (3) until the light absorption coefficient converges to a true value. Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy. Furthermore, since the light absorption coefficient is calculated by the integrated value of the optical path length between the times τ1 and τ2, the influence on the calculation result of the light absorption coefficient due to the error included in the measured light reception intensity can be reduced.

As described above, the embodiment of the present invention has been described in detail with reference to the drawings. However, the specific configuration is not limited to the above, and various design changes and the like can be made without departing from the scope of the present invention. It is possible to
For example, in the first embodiment and the second embodiment, the case where the concentration determination method is implemented in the blood glucose level measurement device 100 and the concentration of glucose contained in the dermis layer of the skin is measured has been described. 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.

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

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

  In the above embodiment, the observation target has been described with a layer configuration, but the present invention can also be applied to a target configured with a lattice (mesh configuration).

DESCRIPTION OF SYMBOLS 100 ... Blood glucose level measuring apparatus (concentration determination apparatus), 101 ... Simulation part, 102 ... Optical path length distribution storage part (optical path length distribution storage means), 103 ... Time-resolved waveform storage part (time-resolved waveform storage means), 104 ... Optical path Long variation storage unit (optical path length variation storage unit), 105 ... Irradiation unit (irradiation unit), 106 ... Light receiving unit (light reception unit), 106 ... Measurement light intensity acquisition unit (light intensity acquisition unit), 109 ... Optical path length acquisition unit (Optical path length acquisition means), 110 ... non-absorption light intensity acquisition section (light intensity model acquisition means), 111 ... light absorption coefficient calculation section (light absorption coefficient calculation means), 113 ... concentration calculation section (concentration calculation means)

Claims (15)

A concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers,
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 a time-resolved waveform of short-time pulsed light irradiated to the observation object;
Optical path length variation storage means for storing variation in optical path length in each of the layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation object;
Irradiating means for irradiating the observation object with short-time pulsed light;
A light receiving means for receiving the light back-scattered by the observation object by the short-time pulsed light;
A light intensity acquisition means for acquiring the intensity of the light received by the light receiving means at a predetermined time after the time when the irradiation means irradiated the short-time pulse light;
An optical path length acquisition means for acquiring an optical path length of each of the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage means;
A light intensity model acquisition means for acquiring 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 acquired by the light intensity acquisition means, the optical path length of each of the layers of the light scattering medium acquired by the optical path length acquisition means, and the light intensity model acquired by the light intensity model acquisition means; A light absorption coefficient calculating means for calculating a light absorption coefficient of the arbitrary layer based on the optical path length variation of each of the layers of the plurality of light scattering media stored in the optical path length variation storage means; ,
Based on the light absorption coefficient calculated by the light absorption coefficient calculation means, a concentration calculation means for calculating the concentration of the target component in the arbitrary layer;
Concentration determination apparatus characterized by including. The observation object consists of a laminated structure of n layers or more,
The light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t), the light intensity received by the light receiving means at time t is I (t), and the light absorption coefficient of the m-th layer is μ _am , the m-th layer of the optical path length L _m at time t of the model of the propagation optical path length distribution _(t), the number of incident photons N _in, the incident light intensity I _in, the m-th layer of the optical path length variation [delta] _miles ( t),
The light intensity acquisition means acquires light intensity at a plurality of times t _{1 to} t _m ,
The light absorption coefficient calculating means calculates an approximate solution of the light absorption coefficient of an arbitrary layer from the following equation (1), and substitutes the approximate solution into the left side of the following equation (2) to calculate the light of the arbitrary layer. The primary correction value of the absorption coefficient is calculated, and the primary correction value is substituted into the left side of the following equation (2) to calculate the secondary correction value of the optical absorption coefficient of the arbitrary layer. Calculate the light absorption coefficient of any layer by repeating until it converges to the true value of the coefficient,
The concentration determination apparatus according to claim 1, wherein:

The observation object consists of a laminated structure of n layers or more,
The light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t), the light intensity received by the light receiving means at time t is I (t), and the light absorption coefficient of the m-th layer is μ _am , the m-th layer of the optical path length L _m at time t of the model of the propagation optical path length distribution _(t), the number of incident photons N _in, the incident light intensity I _in, the m-th layer of the optical path length variation [delta] _miles ( t),
The light intensity acquisition means acquires the light intensity between a predetermined time and at least a predetermined time τ1 to τ2,
The light absorption coefficient calculating means calculates an approximate solution of the light absorption coefficient of an arbitrary layer from the following expression (1) or its integral expression, and substitutes the approximate solution for the left side of the following expression (3). Calculating a primary correction value of the light absorption coefficient of an arbitrary layer and substituting the primary correction value into the left side of the following equation (3) to calculate a secondary correction value of the optical absorption coefficient of the arbitrary layer. Calculate the light absorption coefficient of any layer by repeating until it converges to the true value of the light absorption coefficient of any layer,
The concentration determination apparatus according to claim 1, wherein:

  Based on the light absorption coefficient in the arbitrary layer, the concentration calculation means creates a calibration curve from a value obtained by measuring a characteristic whose characteristics are known using multivariate analysis, and obtains a measurement value of an unknown measurement target. The concentration determination apparatus according to claim 1, wherein the concentration of the target component in the arbitrary layer is calculated by collating with a calibration curve.   5. The concentration of glucose contained in the dermis layer is quantified when the observation target is skin and the arbitrary layer is a dermis layer. 6. Concentration determination device. A light absorption coefficient calculation method for calculating a light absorption coefficient in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers,
A model of propagation 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, time-resolved waveform of the short-time pulse light irradiated to the observation target Model, variation in optical path length in each of the layers of the plurality of light scattering media, and a predetermined time after the time when the irradiation means irradiates the pulse light for a short time. Intensity of light back-scattered by the observation target at the time, the optical path length of each of the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution, A first step of acquiring the light intensity at the predetermined time of the model of the time-resolved waveform of the short-time pulsed light;
Based on the light intensity acquired in the first step, the optical path length of each layer of the plurality of light scattering media, the light intensity model, and the optical path length variation of each layer of the plurality of light scattering media. A second step of calculating a light absorption coefficient of the arbitrary layer;
The light absorption coefficient calculation method characterized by having. The observation object consists of a laminated structure of n layers or more,
The light intensity at time t of the time-resolved waveform model of the short-time pulse light is N (t) , the light intensity received by the light receiving means at time t is I (t), and the light absorption coefficient of the m-th layer is μ _am . In the propagation optical path length distribution model, the optical path length of the m-th layer at time t is L _m (t), the number of incident photons is N _in , the incident light intensity is I _in , and the optical path length variation of the m-th layer is δ _km (t )
In the first step, the light intensity at a plurality of times t _{1 to} t _m is acquired,
In the second step, an approximate solution of the light absorption coefficient of an arbitrary layer is calculated from the following equation (1), and the approximate solution is substituted into the left side of the following equation (2) to absorb the light of the arbitrary layer. Calculating the primary correction value of the coefficient, substituting the primary correction value into the left side of the following equation (2), and calculating the secondary correction value of the optical absorption coefficient of the arbitrary layer. By repeating until it converges to the true value of, calculate the light absorption coefficient of any layer,
The light absorption coefficient calculation method according to claim 6.

The observation object consists of a laminated structure of n layers or more,
The light intensity at time t of the time-resolved waveform model of the short-time pulse light is N (t) , the light intensity received by the light receiving means at time t is I (t), and the light absorption coefficient of the m-th layer is μ _am . In the propagation optical path length distribution model, the optical path length of the m-th layer at time t is L _m (t), the number of incident photons is N _in , the incident light intensity is I _in , and the optical path length variation of the m-th layer is δ _km (t )
In the first step, a light intensity between a predetermined time and at least a predetermined time τ1 to τ2 is acquired,
In the second step, an approximate solution of a light absorption coefficient of an arbitrary layer is calculated from the following equation (1) or its integral equation, and the approximate solution is substituted into the left side of the following equation (3). It is optional to calculate a primary correction value of a light absorption coefficient of an arbitrary layer, and to calculate a secondary correction value of the light absorption coefficient of an arbitrary layer by substituting the primary correction value into the left side of the following equation (3) By repeating until it converges to the true value of the light absorption coefficient of the layer, calculate the light absorption coefficient of any layer,
The light absorption coefficient calculation method according to claim 6.

A concentration determination method, wherein the concentration of a target component in the arbitrary layer is calculated based on the light absorption coefficient calculated in the second step according to any one of claims 6 to 8.   10. The concentration quantification method according to claim 9, wherein when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified. An optical path for storing a model of a propagation path length distribution in each layer of the plurality of light scattering medium layers of short-time pulsed light that irradiates a computer with an observation target formed from the plurality of light scattering medium layers A long distribution storage means;
Time-resolved waveform storage means for storing a model of a time-resolved waveform of short-time pulsed light irradiated to the observation object;
Optical path length variation storage means for storing variation in optical path length in each of the layers of the plurality of light scattering media of the short-time pulse light irradiated to the observation object;
Irradiating means for irradiating a short pulse light to the observation target,
Light receiving means for receiving light the short pulsed light is backscattered by the observed object,
And the light intensity acquisition means the light receiving unit obtains the intensity of the received light at predetermined time after the time of the irradiation unit irradiates the short pulse light,
From the optical path length distribution storage means, in the predetermined time in 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,
From the time-resolved waveform storage means, and the light intensity model acquiring means for acquiring the intensity of the light in the predetermined time in the model of the time-resolved waveform of the short pulse light,
The light intensity acquired by the light intensity acquisition means, the optical path length of each of the layers of the light scattering medium acquired by the optical path length acquisition means, and the light intensity model acquired by the light intensity model acquisition means; A light absorption for calculating a light absorption coefficient of an arbitrary layer among the observation objects based on the optical path length variation of each of the layers of the plurality of light scattering media stored in the optical path length variation storage means and the coefficient calculation means,
A program that calculates the light absorption coefficient to function as The observation object consists of a laminated structure of n layers or more,
The light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t), the light intensity received by the light receiving means at time t is I (t), and the light absorption coefficient of the m-th layer is μ _am , the m-th layer of the optical path length L _m at time t of the model of the propagation optical path length distribution _(t), the number of incident photons N _in, the incident light intensity I _in, the m-th layer of the optical path length variation [delta] _miles ( t),
The light intensity acquisition means acquires light intensity at a plurality of times t _{1 to} t _m ,
The light absorption coefficient calculating means calculates an approximate solution of the light absorption coefficient of an arbitrary layer from the following equation (1), and substitutes the approximate solution into the left side of the following equation (2) to calculate the light of the arbitrary layer. The primary correction value of the absorption coefficient is calculated, and the primary correction value is substituted into the left side of the following equation (2) to calculate the secondary correction value of the optical absorption coefficient of the arbitrary layer. Calculate the light absorption coefficient of any layer by repeating until it converges to the true value of the coefficient,
The program for calculating the light absorption coefficient according to claim 11.

The observation object consists of a laminated structure of n layers or more,
The light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t), the light intensity received by the light receiving means at time t is I (t), and the light absorption coefficient of the m-th layer is μ _am , the m-th layer of the optical path length L _m at time t of the model of the propagation optical path length distribution _(t), the number of incident photons N _in, the incident light intensity I _in, the m-th layer of the optical path length variation [delta] _miles ( t),
The light intensity acquisition means acquires the light intensity between a predetermined time and at least a predetermined time τ1 to τ2,
The light absorption coefficient calculating means calculates an approximate solution of the light absorption coefficient of an arbitrary layer from the following expression (1) or its integral expression, and substitutes the approximate solution for the left side of the following expression (3). Calculating a primary correction value of the light absorption coefficient of an arbitrary layer and substituting the primary correction value into the left side of the following equation (3) to calculate a secondary correction value of the optical absorption coefficient of the arbitrary layer. Calculate the light absorption coefficient of any layer by repeating until it converges to the true value of the light absorption coefficient of any layer,
The program for calculating the light absorption coefficient according to claim 11.

To cause a computer to function as a concentration calculation unit that calculates the concentration of a target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculation unit according to any one of claims 11 to 13. Program to calculate the concentration of the   The program for calculating a concentration according to claim 14, wherein when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified.

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